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Sample records for m-2 a-1 increase

  1. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

    Directory of Open Access Journals (Sweden)

    Paula Mota

    2010-01-01

    Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

  2. Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages

    Science.gov (United States)

    Waqas, Syed F. Hassnain; Hoang, Anh Cuong; Ampem, Grace; Azegrouz, Hind; Balogh, Lajos; Thuróczy, Julianna; Gerling, Ivan C.; Nam, Sorim; Lim, Jong-Seok; Martinez-Ibañez, Juncal; Real, José T.; Paschke, Stephan; Quillet, Raphaëlle; Ayachi, Safia; Simonin, Frédéric; Schneider, E. Marion; Brinkman, Jacqueline A.; Seroogy, Christine M.

    2017-01-01

    The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine. Plasma levels of NPFF decreased in obese patients and high-fat diet–fed mice and increased following caloric restriction. NPFF promoted M2 activation and increased the proliferation of murine and human ATMs. Both M2 activation and increased ATM proliferation were abolished in NPFFR2-deficient ATMs. Mechanistically, the effects of NPFF involved the suppression of E3 ubiquitin ligase RNF128 expression, resulting in enhanced stability of phosphorylated STAT6 and increased transcription of the M2 macrophage–associated genes IL-4 receptor α (Il4ra), arginase 1 (Arg1), IL-10 (Il10), and alkylglycerol monooxygenase (Agmo). NPFF induced ATM proliferation concomitantly with the increase in N-Myc downstream-regulated gene 2 (Ndrg2) expression and suppressed the transcription of Ifi200 cell-cycle inhibitor family members and MAF bZIP transcription factor B (Mafb), a negative regulator of macrophage proliferation. NPFF thus plays an important role in supporting healthy adipose tissue via the maintenance of metabolically beneficial ATMs. PMID:28581443

  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

    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...

  5. 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.

  6. Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

    Science.gov (United States)

    Wilkinson, M; Giles, A; Armour, J A; Cardinal, R

    1996-01-01

    To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

  7. The M2 Channel

    DEFF Research Database (Denmark)

    Santner, Paul

    Drug resistance of Influenza A against antivirals is an increasing problem. No effective Influenza A drugs targeting the crucial viral protein, the proton transporter M2 are available anymore due to widespread resistance. Thanks to research efforts elucidating M2 protein structure, function and i...... 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....

  8. Hypertension and diabetes prevalence among adults with moderately increased BMI (23·0-24·9 kg/m2): findings from a nationwide survey in Bangladesh.

    Science.gov (United States)

    Rahman, Muntasirur; Williams, Gail; Mamun, Abdullah Al

    2017-06-01

    BMI is a proxy for fat accumulation in the body. Increased diabetes and CVD risks have been observed for Asian populations at lower BMI than the WHO-recommended BMI cut-off points for overweight (≥25·0 kg/m2) and obesity (≥30·0 kg/m2). The current study aimed to quantify the increased hypertension (HTN) and type 2 diabetes mellitus (T2DM) prevalence in Bangladeshi adults with moderately increased BMI (23·0-24·9 kg/m2). Data from the most recent Bangladesh Demographic and Health Survey (2011) were analysed. Modified Poisson regression models with robust error variance were used to calculate prevalence ratios (PR) for HTN or T2DM by BMI category, considering BMI=18·5-22·9 kg/m2 as the reference. All analyses incorporated the complex sampling design of the survey. BMI, blood pressure, blood sugar and related information were collected from a nationally representative sample. Adults (n 7433) aged≥35 years. About 12 % of Bangladeshi adults, both male and female, were within the BMI range 23·0-24·9 kg/m2 or moderately overweight. Compared with the reference BMI group (18·5-22·9 kg/m2), they had an increased PR for HTN (1·55-1·77) and T2DM (1·54-1·93). These increased PR are similar to those for the WHO-defined overweight group (BMI=25·0-29·9 kg/m2). Our findings support the recommendation that calls for setting the optimum BMI for Asian populations to 18·5-23·0 kg/m2 for health promotion and for public health interventions like leisure-time physical activity. WHO cut-off points for overweight (≥25 kg/m2) should be used to facilitate international comparisons.

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

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    Cécile Pierre-Eugene

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

  10. Heterotic M2-branes

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    Neil Lambert

    2015-10-01

    Full Text Available We construct the action for N M2-branes on S1/Z2. The resulting theory has a gauge anomaly but this can be cancelled if the two fixed point planes each support 8 chiral Fermions in the fundamental of U(N. Taking the low energy limit leads to the worldsheet theory of N free heterotic strings whose quantization induces an E8 spacetime gauge symmetry on each fixed point plane. Thus this paper presents a non-abelian worldvolume analogue of the classic Hořava–Witten analysis.

  11. Presynaptic muscarinic acetylcholine autoreceptors (M1, M2 and M4 subtypes), adenosine receptors (A1 and A2A) and tropomyosin-related kinase B receptor (TrkB) modulate the developmental synapse elimination process at the neuromuscular junction.

    Science.gov (United States)

    Nadal, Laura; Garcia, Neus; Hurtado, Erica; Simó, Anna; Tomàs, Marta; Lanuza, Maria A; Santafé, Manel; Tomàs, Josep

    2016-06-23

    The development of the nervous system involves an initially exuberant production of neurons that make an excessive number of synaptic contacts. The initial overproduction of synapses promotes connectivity. Hebbian competition between axons with different activities (the least active are punished) leads to the loss of roughly half of the overproduced elements and this refines connectivity and increases specificity. The neuromuscular junction is innervated by a single axon at the end of the synapse elimination process and, because of its relative simplicity, has long been used as a model for studying the general principles of synapse development. The involvement of the presynaptic muscarinic ACh autoreceptors may allow for the direct competitive interaction between nerve endings through differential activity-dependent acetylcholine release in the synaptic cleft. Then, the most active ending may directly punish the less active ones. Our previous results indicate the existence in the weakest axons on the polyinnervated neonatal NMJ of an ACh release inhibition mechanism based on mAChR coupled to protein kinase C and voltage-dependent calcium channels. We suggest that this mechanism plays a role in the elimination of redundant neonatal synapses. Here we used confocal microscopy and quantitative morphological analysis to count the number of brightly fluorescent axons per endplate in P7, P9 and P15 transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice. We investigate the involvement of individual mAChR M1-, M2- and M4-subtypes in the control of axonal elimination after the Levator auris longus muscle had been exposed to agonist and antagonist in vivo. We also analysed the role of adenosine receptor subtypes (A1 and A2A) and the tropomyosin-related kinase B receptor. The data show that postnatal axonal elimination is a regulated multireceptor mechanism that guaranteed the monoinnervation of the neuromuscular synapses. The three receptor sets considered (mAChR, AR and TrkB receptors

  12. Homogeneous M2 duals

    International Nuclear Information System (INIS)

    Figueroa-O’Farrill, José; Ungureanu, Mara

    2016-01-01

    Motivated by the search for new gravity duals to M2 branes with N>4 supersymmetry — equivalently, M-theory backgrounds with Killing superalgebra osp(N|4) for N>4 — we classify (except for a small gap) homogeneous M-theory backgrounds with symmetry Lie algebra so(n)⊕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 AdS 4 ×P 7 , with P riemannian and homogeneous under the action of SO(5), or S 4 ×Q 7 with Q lorentzian and homogeneous under the action of 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.

  13. Homogeneous M2 duals

    Energy Technology Data Exchange (ETDEWEB)

    Figueroa-O’Farrill, José [School of Mathematics and Maxwell Institute for Mathematical Sciences,The University of Edinburgh,James Clerk Maxwell Building, The King’s Buildings, Peter Guthrie Tait Road,Edinburgh EH9 3FD, Scotland (United Kingdom); Ungureanu, Mara [Humboldt-Universität zu Berlin, Institut für Mathematik,Unter den Linden 6, 10099 Berlin (Germany)

    2016-01-25

    Motivated by the search for new gravity duals to M2 branes with N>4 supersymmetry — equivalently, M-theory backgrounds with Killing superalgebra osp(N|4) for N>4 — we classify (except for a small gap) homogeneous M-theory backgrounds with symmetry Lie algebra so(n)⊕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 AdS{sub 4}×P{sup 7}, with P riemannian and homogeneous under the action of SO(5), or S{sup 4}×Q{sup 7} with Q lorentzian and homogeneous under the action of SO(3,2). At least one of the new backgrounds is supersymmetric (albeit with only N=2) and we show that it can be constructed from a supersymmetric Freund-Rubin background via a Wick rotation. Two of the new backgrounds have only been approximated numerically.

  14. M2 to D2

    International Nuclear Information System (INIS)

    Mukhi, Sunil; Papageorgakis, Constantinos

    2008-01-01

    We examine the recently proposed ''3-algebra'' field theory for multiple M2-branes and show that when a scalar field valued in the 3-algebra develops a vacuum expectation value, the resulting Higgs mechanism has the novel effect of promoting topological (Chern-Simons) to dynamical (Yang-Mills) gauge fields. This leads to a precise derivation of the maximally supersymmetric Yang-Mills theory on multiple D2-branes and thereby provides a relationship between 3-algebras and Yang-Mills theories. We discuss the physical interpretation of this result.

  15. 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 preeclampsia. Fetal plasma 27-OHC levels were decreased in preeclamptic samples ( P preeclampsia ( P = 0.04). Placental 27-OHC concentrations were also raised in preeclampsia ( P 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.

  16. Towards Horizontal Architecture for Autonomic M2M Service Networks

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    Juhani Latvakoski

    2014-05-01

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

  17. A Survey on M2M Service Networks

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    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.

  18. M2 polarization enhances silica nanoparticle uptake by macrophages

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    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

  19. A proposal for M2-brane-anti-M2-brane action

    International Nuclear Information System (INIS)

    Garousi, Mohammad R.

    2010-01-01

    We propose a manifestly SO(8) invariant BF type Lagrangian for describing the dynamics of M2-brane-anti-M2-brane system in flat spacetime. When one of the scalars which satisfies a free-scalar equation takes a large expectation value, the M2-brane-anti-M2-brane action reduces to the tachyon DBI action of D2-brane-anti-D2-brane system in flat spacetime.

  20. 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

  1. 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.

  2. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M [Santa Fe, NM

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  3. Statins are independently associated with increased HbA1c in type 1 diabetes

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Andersen, Henrik Ullits; Rossing, Peter

    2016-01-01

    AIMS: Statin use has been associated with increased risk of developing type 2 diabetes (T2DM), and with impaired glycemic control in T2DM patients. The association between statin use and glycemic control in type 1 diabetes (T1DM) is unknown. The association between use of statins and glycemic con...

  4. Increased importance of methane reduction for a 1.5 degree target

    Science.gov (United States)

    Collins, William J.; Webber, Christopher P.; Cox, Peter M.; Huntingford, Chris; Lowe, Jason; Sitch, Stephen; Chadburn, Sarah E.; Comyn-Platt, Edward; Harper, Anna B.; Hayman, Garry; Powell, Tom

    2018-04-01

    To understand the importance of methane on the levels of carbon emission reductions required to achieve temperature goals, a processed-based approach is necessary rather than reliance on the transient climate response to emissions. We show that plausible levels of methane (CH4) mitigation can make a substantial difference to the feasibility of achieving the Paris climate targets through increasing the allowable carbon emissions. This benefit is enhanced by the indirect effects of CH4 on ozone (O3). Here the differing effects of CH4 and CO2 on land carbon storage, including the effects of surface O3, lead to an additional increase in the allowable carbon emissions with CH4 mitigation. We find a simple robust relationship between the change in the 2100 CH4 concentration and the extra allowable cumulative carbon emissions between now and 2100 (0.27 ± 0.05 GtC per ppb CH4). This relationship is independent of modelled climate sensitivity and precise temperature target, although later mitigation of CH4 reduces its value and thus methane reduction effectiveness. Up to 12% of this increase in allowable emissions is due to the effect of surface ozone. We conclude early mitigation of CH4 emissions would significantly increase the feasibility of stabilising global warming below 1.5 °C, alongside having co-benefits for human and ecosystem health.

  5. Main: 1M2Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Casein Kinase Ii, Alpha Chain; Chain: A; Fragment: Catlytic Subunit; Synonym: Ckii; Engineered: Yes Tr...ansferase 2.7.1.37 (Casein Kinase Ii, Alpha Chain) E.De Moliner, S.Sarno, S.Moro, G.Zagotto, G.Zanotti, L.A....=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

  6. MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1

    International Nuclear Information System (INIS)

    Ziaei, Samira; Shimada, Naoko; Kucharavy, Herman; Hubbard, Karen

    2012-01-01

    Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is an RNA-binding protein that modulates splice site usage, polyadenylation, and cleavage efficiency. This protein has also been implicated in mRNA stability and transport from the nucleus. We have previously demonstrated that hnRNP A1 had diminished protein levels and showed cytoplasmic accumulation in senescent human diploid fibroblasts. Furthermore, we have shown that inhibition of p38 MAPK, a key regulator of cellular senescence, elevated hnRNP A1 protein levels and inhibited hnRNP A1 cytoplasmic localization. In this study, we have explored the possible involvement of MNK1, one of the downstream effector of p38 MAPK, in the regulation of hnRNP A1. We have demonstrated that pharmacological inhibition of MNK1 by CGP 57380 decreased the phosphorylation levels of hnRNP A1 in young and senescent fibroblast cells and blocked the cytoplasmic accumulation of hnRNP A1 in senescent cells. In addition, MNK1 formed a complex with hnRNP A1 in vivo. The expression levels of MNK1, phospho-MNK1, and phospho-eIF4E proteins were found to be elevated in senescent cells. These data suggest that MNK1 regulates the phosphorylation and the subcellular distribution of hnRNP A1 and that MNK1 may play a role in the induction of senescence. -- Highlights: ► MNK1 and not MAPKAPK2 phosphorylates hnRNP A1. ► MNK1 has elevated levels in senescent cells, this has not been reported previously. ► MNK1 activity induces cytoplasmic accumulation of hnRNP A1 in senescent cells. ► Altered cytoplasmic localization of hnRNP A1 may alter gene expression patterns. ► Our studies may increase our understanding of RNA metabolism during cellular aging.

  7. 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.

  8. 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.

  9. Defining a glycated haemoglobin (HbA1c) level that predicts increased risk of penile implant infection.

    Science.gov (United States)

    Habous, Mohamad; Tal, Raanan; Tealab, Alaa; Soliman, Tarek; Nassar, Mohammed; Mekawi, Zenhom; Mahmoud, Saad; Abdelwahab, Osama; Elkhouly, Mohamed; Kamr, Hatem; Remeah, Abdallah; Binsaleh, Saleh; Ralph, David; Mulhall, John

    2018-02-01

    To re-evaluate the role of diabetes mellitus (DM) as a risk factor for penile implant infection by exploring the association between glycated haemoglobin (HbA1c) levels and penile implant infection rates and to define a threshold value that predicts implant infection. We conducted a multicentre prospective study including all patients undergoing penile implant surgery between 2009 and 2015. Preoperative, perioperative and postoperative management were identical for the entire cohort. Univariate analysis was performed to define predictors of implant infection. The HbA1c levels were analysed as continuous variables and sequential analysis was conducted using 0.5% increments to define a threshold level predicting implant infection. Multivariable analysis was performed with the following factors entered in the model: DM, HbA1C level, patient age, implant type, number of vascular risk factors (VRFs), presence of Peyronie's disease (PD), body mass index (BMI), and surgeon volume. A receiver operating characteristic (ROC) curve was generated to define the optimal HbA1C threshold for infection prediction. In all, 902 implant procedures were performed over the study period. The mean patient age was 56.6 years. The mean HbA1c level was 8.0%, with 81% of men having a HbA1c level of >6%. In all, 685 (76%) implants were malleable and 217 (24%) were inflatable devices; 302 (33.5%) patients also had a diagnosis of PD. The overall infection rate was 8.9% (80/902). Patients who had implant infection had significantly higher mean HbA1c levels, 9.5% vs 7.8% (P HbA1c level, we found infection rates were: 1.3% with HbA1c level of 9.5% (P HbA1c level, whilst a high-volume surgeon had a protective effect and was associated with a reduced infection risk. Using ROC analysis, we determined that a HbA1c threshold level of 8.5% predicted infection with a sensitivity of 80% and a specificity of 65%. Uncontrolled DM is associated with increased risk of infection after penile implant surgery

  10. Characteristics and potential role of M2 macrophages in COPD

    Directory of Open Access Journals (Sweden)

    He S

    2017-10-01

    Full Text Available Shengyang He, Lihua Xie, Junjuan Lu, Shenghua SunDepartment of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China Background: COPD is a multi-pathogenesis disease mainly caused by smoking. A further understanding of the mechanism of smoking-related COPD might contribute to preventions and treatments of this disease in the early stages. This study was designed to identify the characteristics of M2 macrophages in COPD for a better understanding about their potential role.Materials and methods: COPD models were built in the C57BL/6 mouse by cigarette smoke (CS exposure combined with intraperitoneal injection of cigarette smoke extract (CSE. The modeling efficiency was evaluated by lung function and hematoxylin and eosin (H&E staining. The number of different macrophage phenotypes was detected by immunohistochemical staining (IHS of CD206, CD86 and CD68 on the lung tissue paraffin section. The RAW264.7 cells were polarized toward the M2 phenotype by interleukin IL-4 and confirmed by a flow cytometer. The gene expression levels of TGF-βRII, Smad2, Smad3 and Smad7 in CSE-treated M2 macrophages were detected by real-time reverse transcription polymerase chain reaction (RT-PCR. The expression levels of TGF-β/Smad pathway-related makers (TGF-βRII, p-Smad2, p-Smad3, Smad7 and TGF-β in alveolar M2 macrophages were detected by two consecutive paraffin section IHS.Results: The COPD model is well established, which is confirmed by the lung function test and lung H&E staining. The whole number of macrophages and the ratio of M2/M1 phenotype are both increased (p<0.05. The level of CD206+ cells in IL-4-stimulated RAW264.7 cells is up to 93.4%, which is confirmed by a flow cytometer. The gene expression of TGF-βRII, Smad2, Smad3 and Smad7 are all enhanced (p<0.05 in CES-treated M2 macrophages, which is detected by RT-PCR. The protein levels of TGF-β/Smad pathway-related markers are

  11. 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...

  12. M2 qualify laser beam propagation

    International Nuclear Information System (INIS)

    Abdelhalim, Bencheikh; Mohamed, Bouafia

    2010-01-01

    One of the most important properties of a laser resonator is the highly collimated or spatially coherent nature of the laser output beam. Laser beam diameter and quality factor M 2 are significant parameters in a wide range of laser applications. This is because the spatial beam quality determines how closely the beam can be focused or how well the beam propagates over long distances without significant dispersion. In the present paper we have used three different methods to qualify the spatial structure of a laser beam propagating in free space, the results are obtained and discussed, and we have found that the Wigner distribution function is a powerful tool which allows a global characterization of any kind of beam

  13. Deletions at SLC18A1 increased the risk of CRC and lower SLC18A1 expression associated with poor CRC outcome.

    Science.gov (United States)

    Zhang, Dandan; Li, Zhenli; Xu, Xiaohong; Zhou, Dan; Tang, Shunli; Yin, Xiaoyang; Xu, Fangying; Li, Hui; Zhou, Yuan; Zhu, Tao; Deng, Hong; Zhang, Shuai; Huang, Qiong; Wang, Jing; Yin, Wei; Zhu, Yimin; Lai, Maode

    2017-10-26

    Copy number variations (CNVs) contribute to the development of colorectal cancer (CRC). We conducted a two-stage association study to identify CNV risk loci for CRC. We performed a gene-based rare CNV study on 694 sporadic CRC and 1641 controls using Illumina Human-OmniExpress-12v1.0 BeadChips, and further replicated in 934 CRC cases and 2680 controls for risk CNVs by using TaqMan Copy Number Assay. Tumor buddings, cancer cells in the center of primary tumor and normal intestinal epithelial cells were captured using laser capture microdissection (LCM) and were assayed using AffymetrixGeneChip® Human Genome U133 Plus 2.0 Array. In addition, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus data were assessed for the effects of risk CNVs. We found that germline deletions affecting the last six exons of SLC18A1 significantly associated with CRC with a combined P value of 6.4 × 10-5 by a two-stage analysis. Both in TCGA CRC RNA seq dataset and GDS4382, SLC18A1 was significantly down regulated in CRC tissues than in paired normal tissues (N = 32 and 17 pairs, P = 0.004 and 0.009, respectively). In LCM samples, similar observations were obtained that the expression levels of SLC18A1 in the tumor buddings, cancer cells in the center of primary tumor, and stroma of both tumor budding and cancer cells were lower than normal intestinal epithelial and stromal cells (fold change = 0.17-0.62, 0.12-0.57 and 0.37-0.68, respectively). In summary, the germline deletions at SLC18A1 contributed to the development of CRC. The role of SLC18A1 required further exploration. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Ethanol-induced increase in portal blood flow: Role of acetate and A1- and A2-adenosine receptors

    International Nuclear Information System (INIS)

    Carmichael, F.J.; Saldivia, V.; Varghese, G.A.; Israel, Y.; Orrego, H.

    1988-01-01

    The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A 1 -adenosine receptor agonist N-6-cyclohexyl adenosine and the A 2 -agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A 2 -subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues

  15. M2M Optimizations in Public Mobile Networks

    NARCIS (Netherlands)

    Norp, A.H.J.; Landais, B.

    2012-01-01

    Many M2M applications use public telecommunications networks to transfer data from M2M devices to an M2M server. These telecommunications networks will have to be adapted to cope with the traffic generated by the projected growth of M2M applications. In the near future, many more devices will be

  16. Penrose limits, pp waves, and deformed M2-branes

    International Nuclear Information System (INIS)

    Cvetic, M.; Lue, H.; Pope, C.N.

    2004-01-01

    Motivated by the recent discussions of the Penrose limit of AdS 5 xS 5 , we examine a more general class of supersymmetric pp-wave solutions of the type IIB theory, with a larger number of nonvanishing structures in the self-dual 5-form. One of the pp-wave solutions can be obtained as a Penrose limit of a D3-D3 intersection. In addition to 16 standard supersymmetries these backgrounds always allow for supernumerary supersymmetries. The latter are in one-to-one correspondence with the linearly realized world-sheet supersymmetries of the corresponding exactly solvable type IIB string action. The pp-waves provide new examples where supersymmetries will survive in a T-duality transformation on the x + coordinate. The T-dual solutions can be lifted to give supersymmetric deformed M2-branes in D=11. The deformed M2-brane is dual to a three-dimensional field theory whose renormalization group flow runs from the conformal fixed point in the infrared regime to a nonconformal theory as the energy increases. At a certain intermediate energy scale there is a phase transition associated with a naked singularity of the M2-brane. In the ultraviolet limit the theory is related by T duality to an exactly solvable massive type IIB string theory

  17. 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.

  18. Selective attenuation of norepinephrine release and stress-induced heart rate increase by partial adenosine A1 agonism.

    Directory of Open Access Journals (Sweden)

    Lorenz Bott-Flügel

    Full Text Available The release of the neurotransmitter norepinephrine (NE is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR, NE release was induced by electrical stimulation under control conditions (S1, and with capadenoson 6 · 10(-8 M (30 µg/l, 6 · 10(-7 M (300 µg/l or 2-chloro-N(6-cyclopentyladenosine (CCPA 10(-6 M (S2. Under control conditions (S1, NE release was significantly higher in SHR hearts compared to Wistar (766+/-87 pmol/g vs. 173+/-18 pmol/g, p<0.01. Capadenoson led to a concentration-dependent decrease of the stimulation-induced NE release in SHR (S2/S1  =  0.90 ± 0.08 with capadenoson 6 · 10(-8 M, 0.54 ± 0.02 with 6 · 10(-7 M, but not in Wistar hearts (S2/S1  =  1.05 ± 0.12 with 6 · 10(-8 M, 1.03 ± 0.09 with 6 · 10(-7 M. CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [(35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/-2% A(1-receptor stimulation. These results suggest that partial adenosine A(1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release.

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

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

  20. 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

    , and Neisseria meningitidis, of which the first mentioned species was mainly responsible for the difference observed at the 18-mo examination. Percentage proportions of IgA1 protease-producing bacteria were significantly related to passive smoking which may stimulate the premature and more pronounced pharyngeal...

  1. 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.)

  2. Anxiety sensitivity predicts increased perceived exertion during a 1-mile walk test among treatment-seeking smokers.

    Science.gov (United States)

    Farris, Samantha G; Uebelacker, Lisa A; Brown, Richard A; Price, Lawrence H; Desaulniers, Julie; Abrantes, Ana M

    2017-12-01

    Smoking increases risk of early morbidity and mortality, and risk is compounded by physical inactivity. Anxiety sensitivity (fear of anxiety-relevant somatic sensations) is a cognitive factor that may amplify the subjective experience of exertion (effort) during exercise, subsequently resulting in lower engagement in physical activity. We examined the effect of anxiety sensitivity on ratings of perceived exertion (RPE) and physiological arousal (heart rate) during a bout of exercise among low-active treatment-seeking smokers. Adult daily smokers (n = 157; M age  = 44.9, SD = 11.13; 69.4% female) completed the Rockport 1.0 mile submaximal treadmill walk test. RPE and heart rate were assessed during the walk test. Multi-level modeling was used to examine the interactive effect of anxiety sensitivity × time on RPE and on heart rate at five time points during the walk test. There were significant linear and cubic time × anxiety sensitivity effects for RPE. High anxiety sensitivity was associated with greater initial increases in RPE during the walk test, with stabilized ratings towards the last 5 min, whereas low anxiety sensitivity was associated with lower initial increase in RPE which stabilized more quickly. The linear time × anxiety sensitivity effect for heart rate was not significant. Anxiety sensitivity is associated with increasing RPE during moderate-intensity exercise. Persistently rising RPE observed for smokers with high anxiety sensitivity may contribute to the negative experience of exercise, resulting in early termination of bouts of prolonged activity and/or decreased likelihood of future engagement in physical activity.

  3. 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.

  4. 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.

  5. A distributed approach for secure M2M communications

    OpenAIRE

    BEN SAIED , Yosra; OLIVEREAU , Alexis; LAURENT , Maryline

    2012-01-01

    International audience; A key establishment solution for heterogeneous Machine to Machine (M2M) communications is proposed. Decentralization in M2M environment leads to situations where highly resource-constrained nodes have to establish end-to-end secured contexts with powerful remote servers, which would normally be impossible because of the technological gap between these classes of devices. This paper proposes a novel collaborative session key exchange method, wherein a highly resource-co...

  6. LEU WWR-M2 fuel assemblies burnable test

    International Nuclear Information System (INIS)

    Kirsanov, G.A.; Konoplev, K.A.; Pikulik, R.G.; Sajkov, Yu. P.; Tchmshkyan, D.V.; Tedoradze, L.V.; Zakharov, A.S.

    2000-01-01

    The results of in-pile irradiation tests of LEU WWR-M2 fuel assemblies with reduced enrichment of fuel are submitted in the report. The tests are made according to the Russian Program on Reduced Enrichment for Research and Test Reactors (RERTR). United States Department of Energy and the Ministry of Atomic Energy of Russian Federation jointly fund this Program. The irradiation tests of 5 WWR-M2 experimental assemblies are carried out at WWR-M reactor of the Petersburg Nuclear Physics Institute (PNPI). The information on assembly design and technique of irradiation tests is presented. In the irradiation tests the integrity of fuel assemblies is periodically measured. The report presents the data for the integrity maintained during the burnup of 5 fuel assemblies up to 45%. These results demonstrate the high reliability of the experimental fuel assemblies within the guaranteed burnup limits specified by the manufacturer. The tests are still in progress; it is planned to test and analyze the change in integrity for burnup of up to 70% - 75% or more. LEU WWR-M2 fuel assemblies are to be offered for export by their Novosibirsk manufacturer. Currently, HEU WWR-M2 fuel assemblies are used in Hungary, Ukraine and Vietnam. LEU WWR-M2 fuel assemblies were designed as a possible replacement for the HEU WWR-M2 fuel assemblies in those countries, but their use can be extended to other research reactors. (author)

  7. Ab initio study of M2AlN (M = Ti,V,Cr)

    International Nuclear Information System (INIS)

    Sun, Zhimei; Music, Denis; Ahuja, Rajeev; Schneider, Jochen M

    2005-01-01

    We have studied M 2 AlN phases, where M = Ti, V, and Cr, by means of ab initio total energy calculations. The bulk modulus of M 2 AlN increases as Ti is replaced with V and Cr by 19.0% and 26.5%, respectively, which can be understood on the basis of the increased number of valence electrons filling the p-d hybridized bonding states. The bulk modulus of M 2 AlN is generally higher than that of the corresponding M 2 AlC phase, which may be explained by an extra electron in the former phases contributing to stronger chemical bonding. This work is important for fundamental understanding of elastic properties of these ternary nitrides and may inspire future experimental research. (letter to the editor)

  8. Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

    Science.gov (United States)

    Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

    2014-01-01

    Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1A1 were measured. Results LPA and ApoA1 levels were higher in cases than controls and predictive of case status. LPA increased the odds by 13% while ApoA1 increased the odds by 29% of an FEV1A1 are predictive of a significantly increased risk of developing an FEV1

  9. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cells revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.

  10. Caffeine Increases Apolipoprotein A-1 and Paraoxonase-1 but not Paraoxonase-3 Protein Levels in Human-Derived Liver (HepG2) Cells.

    Science.gov (United States)

    Sayılan Özgün, Gülben; Özgün, Eray; Tabakçıoğlu, Kıymet; Süer Gökmen, Selma; Eskiocak, Sevgi; Çakır, Erol

    2017-12-01

    Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 are antioxidant and anti-atherosclerotic structural high-density lipoprotein proteins that are mainly synthesized by the liver. No study has ever been performed to specifically examine the effects of caffeine on paraoxonase enzymes and on liver apolipoprotein A-1 protein levels. To investigate the dose-dependent effects of caffeine on liver apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels. In vitro experimental study. HepG2 cells were incubated with 0 (control), 10, 50 and 200 μM of caffeine for 24 hours. Cell viability was evaluated by 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Apolipoprotein A-1, paraoxonase-1 and paraoxonase-3 protein levels were measured by western blotting. We observed a significant increase on apolipoprotein A-1 and paraoxonase-1 protein levels in the cells incubated with 50 µM of caffeine and a significant increase on paraoxonase-1 protein level in the cells incubated with 200 µM of caffeine. Our study showed that caffeine does not change paraoxonase-3 protein level, but the higher doses used in our study do cause an increase in both apolipoprotein A-1 and paraoxonase-1 protein levels in liver cells.

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

    Directory of Open Access Journals (Sweden)

    Yi-Rang Na

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

  12. Polarized M2 macrophages in dogs with visceral leishmaniasis.

    Science.gov (United States)

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

    2016-08-15

    The objective of the present study was to analyze the skin (nasal surface and ear regions), lymph nodes (popliteal and pre-scapular), spleen and liver of dogs with visceral leishmaniasis (VL), in order to investigate the relationship between the parasite load measured as DNA copy number of Alpha gene of DNA polymerase of Leishmania infantum by quantitative PCR and the number of M2 macrophages by immunohistochemistry. A set of 29 naturally infected dogs from an endemic area for VL were sampled and another set of six dogs negative for VL and from a non-endemic area were analyzed as the control group (C). The spleen presented the highest number of Leishmania DNA copies, with significant differences between the groups G1 and G2 (with and without skin lesions, respectively). The M2 phenotype immunostaining predominated among the macrophages in granulomas and inflammatory infiltrates of samples from the skin, lymph nodes and spleens examined. The presence of M2 macrophages in dogs from infected group differed significantly from the control group, in all organs analyzed, excepted liver. The highest proportion of M2 macrophages coincided with the highest parasitism loads found in more susceptible organs of VL dogs, even in the skin, considered a more resistant organ, while the liver showed low parasitism load and low immunostaining for M2 macrophages with no significant differences between infected and negative groups. It was concluded that the predominance of M2 phenotype in VL dogs favored the multiplication of Leishmania infantum in organs of dogs that are more susceptible to Leishmania infection, as skin, lymph nodes and spleen. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 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. © International & American Associations for Dental Research 2014.

  14. Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

    Science.gov (United States)

    Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

    2017-07-01

    Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, Padopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

    2002-07-01

    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  16. Increased glycemic variability and decrease of the postprandial glucose contribution to HbA1c in obese subjects across the glycemic continuum from normal glycemia to first time diagnosed diabetes.

    Science.gov (United States)

    Fysekidis, Marinos; Cosson, Emmanuel; Banu, Isabela; Duteil, Régine; Cyrille, Chantal; Valensi, Paul

    2014-12-01

    The contribution of postprandial glycemia (PPG) to hyperglycemia has been shown to decrease as HbA1c increased in type 2 diabetic patients. This study aimed at examining, in a series of overweight/obese patients without known glycemic disorder, the contribution of PPG to a "relative" hyperglycemia (glucose values≥5.5 mmol/L) and the presence of glycemic variability according to HbA1c levels. Seventy overweight/obese inpatients (body mass index 35.2±6.8 kg/m2) without known glycemic disorder were included. Participants were classified according to an oral glucose tolerance test (according to the American Diabetes Association criteria) as patients with normoglycemia (n=33), with intermediate hyperglycemia (n=24) or diabetes (n=13). They were separated into HbA1c quartiles (Q1 to Q4). A 24 hour continuous glucose monitoring was used under a 1800 kcal diet and minimal physical activity. We assessed PPG contribution (3 hour period after each meal) to the "relative" 24 hour hyperglycemia (glucose values ≥5.5 mmol/L); the remaining time was considered as the fasting/post-absorptive period. HbA1c range was from 5.1% to 7.4% (32 to 57 mmol/mmol). From the lowest to the highest HbA1c quartile, the area under the curve (AUC) for the "relative" hyperglycemia presented a 17-fold increase for the fasting/post-absorptive (pAUC-3 h AUC for a constant 5.5 mmol/L glycemia)/(total 24 h AUC-24 h AUC for constant 5. 5 mmol/L glycemia)] and decreased from Q1 to Q4 of HbA1c (81.2%, 66%, 65.8%, 57%; pblood glucose level (pglucose variability indices, including mean amplitude of glycemic excursions (p<0.01). In overweight/obese patients, HbA1c was associated with lower PPG contribution to "relative" hyperglycemia and greater glycemic variability. The present findings support the importance of postprandial period in glycemic exposure even before the appearance of diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. A nonperturbative test of M2-brane theory

    International Nuclear Information System (INIS)

    Hosomichi, Kazuo; Lee, Ki-Myeong; Lee, Sungjay; Yi, Piljin; Lee, Sangmin; Park, Jaemo

    2008-01-01

    We discuss non-perturbative effects in the ABJM model due to monopole instantons. We begin by constructing the instanton solutions in the U(2) x U(2) model, explicitly, and computing the Euclidean action. The Wick-rotated Lagrangian is complex and its BPS monopole instantons are found to be a delicate version of the usual 't Hooft-Polyakov monopole solutions. They are generically 1/3 BPS but become 1/2 BPS at special locus in the moduli space of two M2-branes, yet each instanton carries eight fermionic zero modes, regardless of the vacuum choice. The low energy effective action induced by monopole instantons are quartic order in derivatives. The resulting vertices are nonperturbative in 1/k, as expected, but are rational functions of the vacuum moduli. We also analyze the system of two M2-branes in the supergravity framework and compute the higher order interactions via 11-dimensional supergraviton exchange. The comparison of the two shows that the instanton vertices are precisely reproduced by this M2-brane picture, supporting the proposal that the ABJM model describes multiple M2-branes.

  18. 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

  19. Multiple M2-branes and the embedding tensor

    NARCIS (Netherlands)

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

    2008-01-01

    We show that the Bagger-Lambert theory of multiple M2-branes fits into the general construction of maximally supersymmetric gauge theories using the embedding tensor technique. We apply the embedding tensor technique in order to systematically obtain the consistent gaugings of N = 8 superconformal

  20. An N=1 superfield action for M2 branes

    International Nuclear Information System (INIS)

    Mauri, Andrea; Petkou, Anastasios C.

    2008-01-01

    We present an octonionic N=1 superfield action that reproduces in components the action of Bagger and Lambert for M2 branes. By giving an expectation value to one of the scalars we obtain the maximally supersymmetric superfield action for D2 branes

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

    Directory of Open Access Journals (Sweden)

    Becky J Proskocil

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

  2. Presenting Influenza A M2e Antigen on Recombinant Spores of Bacillus subtilis.

    Directory of Open Access Journals (Sweden)

    Tomasz Łęga

    Full Text Available Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human-avian-swine-human M2e (M2eH-A-S-H peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system.

  3. 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

    Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been...... = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535....

  4. Radiation induced genetic variability studies in M2 and F2M2 generation in chilli (Capsicum annum L.)

    International Nuclear Information System (INIS)

    Rangaiah, S.; Manjunath, A.; Naik, Puttarama; Gangappa, E.

    2002-01-01

    Chilli (Capsicum annum L.) is an important commercial crop in India. Mutation breeding is one of the effective tool to create new variability. Since, yield and its component characters show polygenic inheritance, information on amount of heritable portion of variability created through mutation for these characters is needed to use the induced variability for crop improvement. To harness more variability mutation has been superimposed on hybridization in several crops. The present study is undertaken to estimate the genetic variability induced through gamma irradiation for the polygenically inherited productive traits of chilli in M 2 and F 2 M 2 generation

  5. Adoptive transfer of M2 macrophages reduces neuropathic pain via opioid peptides.

    Science.gov (United States)

    Pannell, Maria; Labuz, Dominika; Celik, Melih Ö; Keye, Jacqueline; Batra, Arvind; Siegmund, Britta; Machelska, Halina

    2016-10-07

    During the inflammation which occurs following nerve damage, macrophages are recruited to the site of injury. Phenotypic diversity is a hallmark of the macrophage lineage and includes pro-inflammatory M1 and anti-inflammatory M2 populations. Our aim in this study was to investigate the ability of polarized M0, M1, and M2 macrophages to secrete opioid peptides and to examine their relative contribution to the modulation of neuropathic pain. Mouse bone marrow-derived cells were cultured as unstimulated M0 macrophages or were stimulated into an M1 phenotype using lipopolysaccharide and interferon-γ or into an M2 phenotype using interleukin-4. The macrophage phenotypes were verified using flow cytometry for surface marker analysis and cytokine bead array for cytokine profile assessment. Opioid peptide levels were measured by radioimmunoassay and enzyme immunoassay. As a model of neuropathic pain, a chronic constriction injury (CCI) of the sciatic nerve was employed. Polarized M0, M1, and M2 macrophages (5 × 10 5 cells) were injected perineurally twice, on days 14 and 15 following CCI or sham surgery. Mechanical and heat sensitivity were measured using the von Frey and Hargreaves tests, respectively. To track the injected macrophages, we also transferred fluorescently stained polarized cells and analyzed the surface marker profile of endogenous and injected cells in the nerves ex vivo. Compared to M0 and M1 cells, M2 macrophages contained and released higher amounts of opioid peptides, including Met-enkephalin, dynorphin A (1-17), and β-endorphin. M2 cells transferred perineurally at the nerve injury site reduced mechanical, but not heat hypersensitivity following the second injection. The analgesic effect was reversed by the perineurally applied opioid receptor antagonist naloxone methiodide. M2 cells did not affect sensitivity following sham surgery. Neither M0 nor M1 cells altered mechanical and heat sensitivity in CCI or sham-operated animals. Tracing the

  6. Increased macroH2A1.1 expression correlates with poor survival of triple-negative breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Anne-Claire Lavigne

    Full Text Available PURPOSE: Epithelial-Mesenchymal Transition (EMT features appear to be key events in development and progression of breast cancer. Epigenetic modifications contribute to the establishment and maintenance of cancer subclasses, as well as to the EMT process. Whether histone variants contribute to these transformations is not known. We investigated the relative expression levels of histone macroH2A1 splice variants and correlated it with breast cancer status/prognosis/types. METHODS: To detect differential expression of macroH2A1 variant mRNAs in breast cancer cells and tumor samples, we used the following databases: GEO, EMBL-EBI and publisher databases (may-august 2012. We extracted macroH2A1.1/macroH2A1 mRNA ratios and performed correlation studies on intrinsic molecular subclasses of breast cancer and on molecular characteristics of EMT. Associations between molecular and survival data were determined. RESULTS: We found increased macroH2A1.1/macroH2A1 mRNA ratios to be associated with the claudin-low intrinsic subtype in breast cancer cell lines. At the molecular level this association translates into a positive correlation between macroH2A1 ratios and molecular characteristics of the EMT process. Moreover, untreated Triple Negative Breast Cancers presenting a high macroH2A1.1 mRNA ratio exhibit a poor outcome. CONCLUSION: These results provide first evidence that macroH2A1.1 could be exploited as an actor in the maintenance of a transient cellular state in EMT progress towards metastatic development of breast tumors.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Udaya S Rangaswamy

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

  9. On relating multiple M2 and D2-branes

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  10. 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases reactive oxygen species production in human endothelial cells via induction of cytochrome P4501A1

    International Nuclear Information System (INIS)

    Kopf, P.G.; Walker, M.K.

    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 hypothesis that TCDD increases reactive oxygen species (ROS) in endothelial cells by the induction of CYP1A1. A concentration-response to 24 h TCDD exposure (10 pM-10 nM) was performed in confluent primary human aortic endothelial cells (HAECs). Oxidant-sensitive fluorescent probes dihydroethidium (DHE) and 2',7'-dichlorofluorescin diacetate (DCFH-DA), were used to measure superoxide anion, and hydrogen peroxide and hydroxyl radical, respectively. NO was also measured using the fluorescent probe diaminofluorescein-2 diacetate (DAF-2DA). These assessments were conducted in HAECs transfected with siRNA targeting the aryl hydrocarbon receptor (AhR), CYP1A1, or CYP1B1. TCDD concentration-dependently increased CYP1A1 and CYP1B1 mRNA, protein, and enzyme activity. Moreover, 1 nM TCDD maximally increased DHE (Cont = 1.0 ± 0.3; TCDD = 5.1 ± 1.0; p = 0.002) and DCFH-DA (Cont = 1.0 ± 0.2; TCDD = 4.1 ± 0.5; p = 0.002) fluorescence and maximally decreased DAF-2DA fluorescence (Cont = 1.0 ± 0.4; TCDD = 0.68 ± 0.1). siRNA targeting AhR and CYP1A1 significantly decreased TCDD-induced DHE (siAhR: Cont = 1.0 ± 0.1; TCDD = 1.3 ± 0.2; p = 0.093) (siCYP1A1: Cont = 1.0 ± 0.1; TCDD = 1.1 ± 0.1; p = 0.454) and DCFH-DA (siAhR: Cont = 1.0 ± 0.2; TCDD = 1.3 ± 0.3; p = 0.370) (siCYP1A1: Cont = 1.0 ± 0.1; TCDD = 1.3 ± 0.2; p = 0.114) fluorescence and increased DAF-2DA fluorescence (siAhR: Cont = 1.00 ± 0.03; TCDD = 0.97 ± 0.03; p = 0.481) (siCYP1A1: Cont = 1.00 ± 0.03; TCDD = 0.92 ± 0

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

    Science.gov (United States)

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

    2016-02-01

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

  12. Highly retarded M2 transition in 90Nb

    International Nuclear Information System (INIS)

    Sergeev, V.O.

    2006-01-01

    One studied properties of 2.3 keV transition between 124.67 (4 - ) and 122.37 keV (6 + ) in 90 Nb. The mentioned M2-transition is shown to be retarded by approximately 10 4 times and provided explanations of the mentioned extraordinary high factor of deceleration. One evaluated impurity of E3 possible multipolarity constituent in the mentioned transition (δ 2 [ru

  13. Solar thermal barometer. 12 million M2 installed in europe

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    European thermal solar has once again reached its zenith. The difficult times of 1985-1995 are now a thing of the past. The best proof is the very good results of 2001 that show figures in significant progression with respect to those of the year 2000. 1480 320 m 2 . This is now the new record to beat in terms of the annual volume of thermal solar collector installation in the European Union. (author)

  14. State-of-the-art Model M-2 Maintenance System

    International Nuclear Information System (INIS)

    Herndon, J.N.; Martin, H.L.; Satterlee, P.E. Jr.; Jelatis, D.G.; Jennrich, C.E.

    1984-04-01

    The Model M-2 Maintenance System is part of an ongoing program within the Consolidated Fuel Reprocessing Program (CFRP) at Oak Ridge National Laboratory (ORNL) to improve remote manipulation technology for future nuclear fuel reprocessing and other remote applications. Techniques, equipment, and guidelines which can improve the efficiency of remote maintenance are being developed. The Model M-2 Maintenance System, installed in the Integrated Equipment Test (IET) Facility at ORNL, provides a complete, integrated remote maintenance system for the demonstration and development of remote maintenance techniques. The system comprises a pair of force-reflecting servomanipulator arms, television viewing, lighting, and auxiliary lifting capabilities, thereby allowing manlike maintenance operations to be executed remotely within the remote cell mockup area in the IET. The Model M-2 Maintenance System incorporates an upgraded version of the proven Central Research Laboratories' Model M servomanipulator. Included are state-of-the-art brushless dc servomotors for improved performance, remotely removable wrist assemblies, geared azimuth drive, and a distributed microprocessor-based digital control system. 5 references, 8 figures

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

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

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

  16. 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

    2008-04-04

    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

  17. Vinclozolin, a widely used fungizide, enhanced BaP-induced micronucleus formation in human derived hepatoma cells by increasing CYP1A1 expression.

    Science.gov (United States)

    Wu, Xin-Jiang; Lu, Wen-qing; Roos, Peter H; Mersch-Sundermann, Volker

    2005-10-15

    Vinclozolin, a widely used fungicide, can be identified as a residue in numerous vegetable and fruit samples. To get insight in its genetic toxicity, we investigated the genotoxic effect of vinclozolin in the human derived hepatoma cell line HepG2 using the micronucleus (MN) assay. Additionally, to evaluate the co- or anti-mutagenic potency of vinclozolin, we treated HepG2 cells with different concentrations of vinclozolin for 24 h. Subsequently, the cells were exposed to benzo[a]pyrene (BaP) for 1h. Exposure of HepG2 cells to 50-400 microM vinclozolin alone did not cause any induction of micronuclei. However, a pronounced co-mutagenic effect was observed. MN frequencies caused by BaP increased by 30.6%, 52.8% and 65.3% after pretreatment of the cell cultures with 50, 100 and 200 microM vinclozolin, respectively. The highest concentration (400 microM) of vinclozolin tested caused cytotoxicity. Therefore, micronuclei were not considered for that concentration. To clarify the mechanism of cogenotoxicity, we assayed cytochrome P450 1A1 (CYP1A1), which plays a pivotal role in activation of BaP. Cells exposed to vinclozolin led to significant increase of CYP1A1 expression in Western blot. The result suggested that induction of CYP1A1 by vinclozolin account for its enhancing effect on genotoxicity caused by BaP.

  18. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity

    NARCIS (Netherlands)

    Korte, S. Mechiel; Prins, Jolanda; van den Bergh, Filip S.; Oosting, Ronald S.; Dupree, Rudy; Korte-Bouws, Gerdien A. H.; Westphal, Koen G. C.; Olivier, Berend; Denys, Damiaan A.; Garland, Alexis; Güntürkün, Onur

    2017-01-01

    The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase

  19. ZMS regulation of M2 muscarinic receptor mRNA stability requires protein factor

    International Nuclear Information System (INIS)

    Zhang Yongfang; Xia Zongqin; Hu Ya'er

    2010-01-01

    Aim The aim of this work is to study the elevation mechanism of ZMS on muscarinic M2 receptor mRNA expression. Methods Actinomycin D was added to cultured CHOm2 cells to stop the de novo synthesis of M2 receptor mRNA and samples were taken at various times to determine the time course of mRNA of M2 receptor with real-time quantitative RT-PCR. Half-life of M2 receptor mRNA and the effect of ZMS on the half-life was obtained from the slope of the exponential curves. Cycloheximide was added at 4 h prior to and 24 h after the addition of ZMS to examine the effect of de novo protein synthesis on the action of ZMS. Results The half-life of m2 mRNA was prolonged by ZMS treatment without cycloheximide (4.75±0.54 h and 2.13 h±0.23 h for ZMS and vehicle treated groups, respectively, P<0.05). When cycloheximide was added to the culture medium 4h prior to the addition of ZMS, the effect of ZMS in prolonging the half-life of m2 mRNA disappeared (3.06 h±0.23 h and 3.00 h±l.20 h for cells with and without ZMS, respectively). However, when the ZMS was added to the medium 24h prior to the addition of cycloheximide, the action of ZMS was not abolished by cycloheximide (half-life was 5.43 h±1.13 h and 2.46 h±0.09 h for cells with and without ZMS, respectively). Conclusion These data suggest that de novo protein synthesis was required for the increase in M2 mRNA stability induced by ZMS. (authors)

  20. 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.

  1. 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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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.

  6. Beta3 adrenoceptors substitute the role of M(2) muscarinic receptor in coping with cold stress in the heart: evidence from M(2)KO mice.

    Science.gov (United States)

    Benes, Jan; Novakova, Martina; Rotkova, Jana; Farar, Vladimir; Kvetnansky, Richard; Riljak, Vladimir; Myslivecek, Jaromir

    2012-07-01

    We investigated the role of beta3-adrenoceptors (AR) in cold stress (1 or 7 days in cold) in animals lacking main cardioinhibitive receptors-M2 muscarinic receptors (M(2)KO). There was no change in receptor number in the right ventricles. In the left ventricles, there was decrease in binding to all cardiostimulative receptors (beta1-, and beta2-AR) and increase in cardiodepressive receptors (beta3-AR) in unstressed KO in comparison to WT. The cold stress in WT animals resulted in decrease in binding to beta1- and beta2-AR (to 37%/35% after 1 day in cold and to 27%/28% after 7 days in cold) while beta3-AR were increased (to 216% of control) when 7 days cold was applied. MR were reduced to 46% and 58%, respectively. Gene expression of M2 MR in WT was not changed due to stress, while M3 was changed. The reaction of beta1- and beta2-AR (binding) to cold was similar in KO and WT animals, and beta3-AR in stressed KO animals did not change. Adenylyl cyclase activity was affected by beta3-agonist CL316243 in cold stressed WT animals but CL316243 had almost no effects on adenylyl cyclase activity in stressed KO. Nitric oxide activity (NOS) was not affected by BRL37344 (beta3-agonist) both in WT and KO animals. Similarly, the stress had no effects on NOS activity in WT animals and in KO animals. We conclude that the function of M2 MR is substituted by beta3-AR and that these effects are mediated via adenylyl cyclase rather than NOS.

  7. 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.

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

    Science.gov (United States)

    Langouche, Lies; Marques, Mirna B; Ingels, Catherine; Gunst, Jan; Derde, Sarah; Vander Perre, Sarah; D'Hoore, André; Van den Berghe, Greet

    2011-01-01

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

  9. SLiM 2: Flexible, Interactive Forward Genetic Simulations.

    Science.gov (United States)

    Haller, Benjamin C; Messer, Philipp W

    2017-01-01

    Modern population genomic datasets hold immense promise for revealing the evolutionary processes operating in natural populations, but a crucial prerequisite for this goal is the ability to model realistic evolutionary scenarios and predict their expected patterns in genomic data. To that end, we present SLiM 2: an evolutionary simulation framework that combines a powerful, fast engine for forward population genetic simulations with the capability of modeling a wide variety of complex evolutionary scenarios. SLiM achieves this flexibility through scriptability, which provides control over most aspects of the simulated evolutionary scenarios with a simple R-like scripting language called Eidos. An example SLiM simulation is presented to illustrate the power of this approach. SLiM 2 also includes a graphical user interface for simulation construction, interactive runtime control, and dynamic visualization of simulation output, facilitating easy and fast model development with quick prototyping and visual debugging. We conclude with a performance comparison between SLiM and two other popular forward genetic simulation packages. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Exploiting the Capture Effect to Enhance RACH Performance in Cellular-Based M2M Communications

    Directory of Open Access Journals (Sweden)

    Jonghun Kim

    2017-09-01

    Full Text Available Cellular-based machine-to-machine (M2M communication is expected to facilitate services for the Internet of Things (IoT. However, because cellular networks are designed for human users, they have some limitations. Random access channel (RACH congestion caused by massive access from M2M devices is one of the biggest factors hindering cellular-based M2M services because the RACH congestion causes random access (RA throughput degradation and connection failures to the devices. In this paper, we show the possibility exploiting the capture effects, which have been known to have a positive impact on the wireless network system, on RA procedure for improving the RA performance of M2M devices. For this purpose, we analyze an RA procedure using a capture model. Through this analysis, we examine the effects of capture on RA performance and propose an Msg3 power-ramping (Msg3 PR scheme to increase the capture probability (thereby increasing the RA success probability even when severe RACH congestion problem occurs. The proposed analysis models are validated using simulations. The results show that the proposed scheme, with proper parameters, further improves the RA throughput and reduces the connection failure probability, by slightly increasing the energy consumption. Finally, we demonstrate the effects of coexistence with other RA-related schemes through simulation results.

  11. Supersymmetric states in M5/M2 CFTs

    International Nuclear Information System (INIS)

    Bhattacharyya, Sayantani; Minwalla, Shiraz

    2007-01-01

    We propose an exact, finite N formula for the partition function over 1/4 th BPS states in the conformal field theory on the world volume of N coincident M5 branes, and 1/8 th BPS states in the theory of N conincident M2 branes. We obtain our partition function by performing the radial quantization of the Coulomb Branches of these theories and rederive the same formula from the quantization of supersymmetric giant and dual giant gravitons in AdS 7 x S 4 and AdS 4 x S 7 . Our partition function is qualitatively similar to the analogous quantity in N = 4 Yang Mills. It reduces to the sum over supersymmetric multi gravitons at low energies, but deviates from this supergravity formula at energies that scale like a positive power of N

  12. TREAT experiment M2 post-test examination

    International Nuclear Information System (INIS)

    Holland, J.W.; Teske, G.M.; Florek, J.C.

    1986-01-01

    Transient Reactor Test (TREAT) Facility experiment M2 was performed to evaluate the transient behavior of metal-alloy fuel under accident conditions to investigate the inherent safety features of the fuel in integral fast reactor (IFR) system designs. Objectives were to obtain early information on the key fuel behavior characteristics at transient overpower (TOP) conditions in metal-fueled fast reactors; namely, margin to cladding breach and extent of axial self-extrusion of fuel within intact cladding. The onset of cladding breaching depends on fuel/cladding eutectic formation, as well as cladding pressurization and melting. Driving forces for fuel extrusion are fission gas, liquid sodium, and volatile fission products trapped within the fuel matrix. The post-test examination provided data essential for correctly modeling fuel behavior in accident codes

  13. 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.

  14. Adenosine A1 receptor activation increases myocardial protein S-nitrosothiols and elicits protection from ischemia-reperfusion injury in male and female hearts.

    Directory of Open Access Journals (Sweden)

    Qin Shao

    Full Text Available Nitric oxide (NO plays an important role in cardioprotection, and recent work from our group and others has implicated protein S-nitrosylation (SNO as a critical component of NO-mediated protection in different models, including ischemic pre- and post-conditioning and sex-dependent cardioprotection. However, studies have yet to examine whether protein SNO levels are similarly increased with pharmacologic preconditioning in male and female hearts, and whether an increase in protein SNO levels, which is protective in male hearts, is sufficient to increase baseline protection in female hearts. Therefore, we pharmacologically preconditioned male and female hearts with the adenosine A1 receptor agonist N6-cyclohexyl adenosine (CHA. CHA administration prior to ischemia significantly improved functional recovery in both male and female hearts compared to baseline in a Langendorff-perfused heart model of ischemia-reperfusion injury (% of preischemic function ± SE: male baseline: 37.5±3.4% vs. male CHA: 55.3±3.2%; female baseline: 61.4±5.7% vs. female CHA: 76.0±6.2%. In a separate set of hearts, we found that CHA increased p-Akt and p-eNOS levels. We also used SNO-resin-assisted capture with LC-MS/MS to identify SNO proteins in male and female hearts, and determined that CHA perfusion induced a modest increase in protein SNO levels in both male (11.4% and female (12.3% hearts compared to baseline. These findings support a potential role for protein SNO in a model of pharmacologic preconditioning, and provide evidence to suggest that a modest increase in protein SNO levels is sufficient to protect both male and female hearts from ischemic injury. In addition, a number of the SNO proteins identified with CHA treatment were also observed with other forms of cardioprotective stimuli in prior studies, further supporting a role for protein SNO in cardioprotection.

  15. The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity.

    Science.gov (United States)

    Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

    2017-01-05

    The 5-HT 1A/1B -receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT 1A/1B -receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Tijana Ivanovic

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

  17. 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

    2012-12-07

    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

  18. 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.

  19. Deficiency of ATP-binding cassette transporters A1 and G1 in macrophages increases inflammation and accelerates atherosclerosis in mice.

    Science.gov (United States)

    Westerterp, Marit; Murphy, Andrew J; Wang, Mi; Pagler, Tamara A; Vengrenyuk, Yuliya; Kappus, Mojdeh S; Gorman, Darren J; Nagareddy, Prabhakara R; Zhu, Xuewei; Abramowicz, Sandra; Parks, John S; Welch, Carrie; Fisher, Edward A; Wang, Nan; Yvan-Charvet, Laurent; Tall, Alan R

    2013-05-24

    Plasma high-density lipoprotein levels are inversely correlated with atherosclerosis. Although it is widely assumed that this is attributable to the ability of high-density lipoprotein to promote cholesterol efflux from macrophage foam cells, direct experimental support for this hypothesis is lacking. To assess the role of macrophage cholesterol efflux pathways in atherogenesis. We developed mice with efficient deletion of the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1) in macrophages (MAC-ABC(DKO) mice) but not in hematopoietic stem or progenitor populations. MAC-ABC(DKO) bone marrow (BM) was transplanted into Ldlr(-/-) recipients. On the chow diet, these mice had similar plasma cholesterol and blood monocyte levels but increased atherosclerosis compared with controls. On the Western-type diet, MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice had disproportionate atherosclerosis, considering they also had lower very low-density lipoprotein/low-density lipoprotein cholesterol levels than controls. ABCA1/G1-deficient macrophages in lesions showed increased inflammatory gene expression. Unexpectedly, Western-type diet-fed MAC-ABC(DKO) BM-transplanted Ldlr(-/-) mice displayed monocytosis and neutrophilia in the absence of hematopoietic stem and multipotential progenitor cells proliferation. Mechanistic studies revealed increased expressions of machrophage colony stimulating factor and granulocyte colony stimulating factor in splenic macrophage foam cells, driving BM monocyte and neutrophil production. These studies show that macrophage deficiency of ABCA1/G1 is proatherogenic likely by promoting plaque inflammation and uncover a novel positive feedback loop in which cholesterol-laden splenic macrophages signal BM progenitors to produce monocytes, with suppression by macrophage cholesterol efflux pathways.

  20. 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...

  1. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    Science.gov (United States)

    Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

  2. Microglia M2A Polarization as Potential Link between Food Allergy and Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Hans O. Kalkman

    2017-12-01

    Full Text Available Atopic diseases are frequently co-morbid with autism spectrum disorders (ASD. Allergic responses are associated with an activation of mast cells, innate lymphoid cells, and Th2 cells. These cells produce type-2 cytokines (IL4 and IL13, which stimulate microglia and macrophages to adopt a phenotype referred to as ‘alternative activation’ or ‘M2A’. M2A-polarized macrophages and microglia play a physiological role in tissue repair by secreting growth factors such as brain-derived neurotrophic factor (BDNF and insulin-like growth factor-1. In ASD there is evidence for increased type-2 cytokines, microglia activation, M2A polarization, and increased levels of growth factors. In neurons, these growth factors drive a signal transduction pathway that leads to activation of the enzyme mammalian Target of Rapamycin (mTOR, and thereby to the inhibition of autophagy. Activation of mTOR is an effect that is also common to several of the genetic forms of autism. In the central nervous system, redundant synapses are removed via an autophagic process. Activation of mTOR would diminish the pruning of redundant synapses, which in the context of ASD is likely to be undesired. Based on this line of reasoning, atopic diseases like food allergy, eczema or asthma would represent risk factors for autism spectrum disorders.

  3. Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma.

    Science.gov (United States)

    Higashi-Kuwata, Nobuyo; Makino, Takamitsu; Inoue, Yuji; Takeya, Motohiro; Ihn, Hironobu

    2009-08-01

    Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor beta. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma.

  4. 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.

  5. 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.

  6. 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

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

    Science.gov (United States)

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

    2013-01-01

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

  8. Report ETSI M2M-14bis JTC March 2011 meeting

    NARCIS (Netherlands)

    Keesmaat, N.W.

    2011-01-01

    The ETSI Technical Committee (TC) M2M focuses on the development of a generic M2M architecture and underlying protocols suitable for a wide range of M2M environments. Whereas in the past effort has been put in the development of several use cases, the focus of this M2M 14bis meeting – held in Sophia

  9. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    Science.gov (United States)

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  10. Identification of M2 macrophages in anterior pituitary glands of normal rats and rats with estrogen-induced prolactinoma.

    Science.gov (United States)

    Fujiwara, Ken; Yatabe, Megumi; Tofrizal, Alimuddin; Jindatip, Depicha; Yashiro, Takashi; Nagai, Ryozo

    2017-05-01

    Macrophages are present throughout the anterior pituitary gland. However, the features and function of macrophages in the gland are poorly understood. Recent studies have indicated that there are two main macrophage classes: M1 (classically activated) and M2 (alternatively activated). In this study, we examine whether both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Our findings indicate that macrophages that are positive for CD68 (a pan-macrophage marker) were localized near capillaries in rat anterior pituitary gland. These macrophages were positive for iNOS or mannose receptor (MR), which are markers of M1 and M2 macrophages, respectively. To determine the morphological characteristics of M2 macrophages under pathological conditions, diethylstilbestrol (DES)-treated rats were used as an animal model of prolactinoma. After 2 weeks of DES treatment, a number of MR-immunopositive cells were present in the gland. Immunoelectron microscopy revealed that MR-immunopositive M2 macrophages had many small vesicles and moderately large vacuoles in cytoplasm. Phagosomes were sometimes present in cytoplasm. Interestingly, M2 macrophages in prolactinoma tissues did not usually exhibit distinct changes or differences during the normal, hyperplasia and adenoma stages. This study is the first to confirm that both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Moreover, the number of M2 macrophages was greatly increased in rats with DES-induced prolactinoma. Future studies should attempt to characterize the functional role of M2 macrophages in the gland.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Qinghe Du

    2016-03-01

    Full Text Available In machine-to-machine (M2M networks, a key challenge is to overcome the overload problem caused by random access requests from massive machine-type communication (MTC devices. When differentiated services coexist, such as delay-sensitive and delay-tolerant services, the problem becomes more complicated and challenging. This is because delay-sensitive services often use more aggressive policies, and thus, delay-tolerant services get much fewer chances to access the network. To conquer the problem, we propose an efficient mechanism for massive access control over differentiated M2M services, including delay-sensitive and delay-tolerant services. Specifically, based on the traffic loads of the two types of services, the proposed scheme dynamically partitions and allocates the random access channel (RACH resource to each type of services. The RACH partition strategy is thoroughly optimized to increase the access performances of M2M networks. Analyses and simulation demonstrate the effectiveness of our design. The proposed scheme can outperform the baseline access class barring (ACB scheme, which ignores service types in access control, in terms of access success probability and the average access delay.

  13. Seasonal variability of the M2 tide in the seas adjacent to Korea

    Science.gov (United States)

    Kang, Sok Kuh; Chung, Jong-yul; Lee, Sang-Ryong; Yum, Ki-Dat

    1995-08-01

    Seasonal variability of the M2 tidal harmonic constants is revealed through analyses of monthly tidal data at 12 representative tidal stations in the seas adjacent to the Korean peninsula. The variability remain systematic over the 9 years (1965-1973) of data analysis with a range comparable to that of the 18.6 year nodal modulation. Spatial inhomogeneity of the seasonal variability in the observed harmonic constants is found to exist. The largest seasonal variability in M2 appears in the stations located along the Korea Strait. This variability is not explained by the equilibrium theory of tides, and such a variability or irregularities in the harmonic constants are considered as either a noise as done by Cartwright and Amin (1986), Deutsch Hydrography Zeitschrift, 39, 235-253, or a manifestation of frictional interaction as done by Godin and Gutierrez (1986) Continental Shelf Research, 5, 379-402 for the Bay of Fundy. Considering the opposite relation between monthly mean sea level differences in Izuhara-Pusan section and tidal characteristics in the Korea Strait, it is hypothesized that the interaction between the predominant tidal currents and oceanic currents varying with the seasons might be the main cause of the observed temporal variability in the M2 tide. The nonlinear effect of the Kuroshio is investigated along the shelf break region through scale analyses, which show that the presence of a mean current increases the non-linear terms in the momentum balance by about one order of magnitude. The seasonally different damping effect of the Tsushima Current to the M2 tide is also discussed to explain the process of dominant seasonal variability along the Korea Strait based on the actual current data, but further thorough investigation, considering the advection effect of the mean current, is required to investigate the associated dynamics more completely.

  14. M2-like macrophage polarization in high lactic acid-producing head and neck cancer.

    Science.gov (United States)

    Ohashi, Toshimitsu; Aoki, Mitsuhiro; Tomita, Hiroyuki; Akazawa, Takashi; Sato, Katsuya; Kuze, Bunya; Mizuta, Keisuke; Hara, Akira; Nagaoka, Hitoshi; Inoue, Norimitsu; Ito, Yatsuji

    2017-06-01

    Reprogramming of glucose metabolism in tumor cells is referred to as the Warburg effect and results in increased lactic acid secretion into the tumor microenvironment. We have previously shown that lactic acid has important roles as a pro-inflammatory and immunosuppressive mediator and promotes tumor progression. In this study, we examined the relationship between the lactic acid concentration and expression of LDHA and GLUT1, which are related to the Warburg effect, in human head and neck squamous cell carcinoma (HNSCC). Tumors expressing lower levels of LDHA and GLUT1 had a higher concentration of lactic acid than those with higher LDHA and GLUT1 expression. Lactic acid also suppressed the expression of LDHA and GLUT1 in vitro. We previously reported that lactic acid enhances expression of an M2 macrophage marker, ARG1, in murine macrophages. Therefore, we investigated the relationship between the lactic acid concentration and polarization of M2 macrophages in HNSCC by measuring the expression of M2 macrophage markers, CSF1R and CD163, normalized using a pan-macrophage marker, CD68. Tumors with lower levels of CD68 showed a higher concentration of lactic acid, whereas those with higher levels of CSF1R showed a significantly higher concentration of lactic acid. A similar tendency was observed for CD163. These results suggest that tumor-secreted lactic acid is linked to the reduction of macrophages in tumors and promotes induction of M2-like macrophage polarization in human HNSCC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

    Directory of Open Access Journals (Sweden)

    Jia Bi

    2016-01-01

    Full Text Available 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.

  16. Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study.

    Science.gov (United States)

    Li, Tsai-Chung; Yang, Chun-Pai; Tseng, Shih-Ting; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chiang, Jen-Huai; Lin, Cheng-Chieh

    2017-09-01

    The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA 1c ) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA 1c and other traditional risk factors in such patients. Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD ( n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA 1c , drug-related variables, and comorbidities, both FPG CV and HbA 1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06-1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11-1.58) for the third tertile in HbA 1c CV. FPG CV and HbA 1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA 1c CV can be valuable therapeutic targets for patients with T2DM at risk. © 2017 by the American Diabetes Association.

  17. Study on surface modification of M2 steel induced by Cu ions and Al ions implantation

    International Nuclear Information System (INIS)

    Wang Chao; Liu Zhengmin

    2001-01-01

    Changes of surface hardness and wear resistances in M2 type steel implanted by Cu Al ions were reported. The dependence of surface strengthening on ion species and dose was studied by X-ray diffraction (XRD) and Rutherford Backscattering Spectroscopy (RBS) for microhardness and wear resistances measurement. It is shown that both hardness and wear resistance increases apparently after ion implantation. XRD analysis indicates that different phases formed after Al Cu ions implanted. It is also suggested that Cu, Al ions have different role in surface strengthening

  18. 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

  19. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

    International Nuclear Information System (INIS)

    Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

    2015-01-01

    Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

  20. 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

    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

  1. M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway

    Science.gov (United States)

    Madsen, Daniel H.; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E.; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S.; Brenner, David A.; Burgdorf, Sven; Engelholm, Lars H.; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto

    2013-01-01

    Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase–dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor–associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. PMID:24019537

  2. Ethanol Extract of Mylabris phalerata Inhibits M2 Polarization Induced by Recombinant IL-4 and IL-13 in Murine Macrophages

    Directory of Open Access Journals (Sweden)

    Hwan-Suck Chung

    2017-01-01

    Full Text Available Mylabris phalerata (MP is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment. In this line, we screened oriental medicines to find M1 polarizing medicines in M2-polarized macrophages. Among approximately 400 types of oriental medicine, the ethanol extract of M. phalerata (EMP was the most proficient in increasing TNF-α secretion in M2-polarized macrophages and TAM. Although EMP enhanced the levels of an M1 cytokine (TNF-α and a marker (CD86, it significantly reduced the levels of an M2 marker (arginase-1 in M2-polarized macrophages. In addition, EMP-treated macrophages increased the levels of M1 markers (Inos and Tnf-α and reduced those of the enhanced M2 markers (Fizz-1, Ym-1, and arginase-1. EMP-treated macrophages significantly reduced Lewis lung carcinoma cell migration in a transwell migration assay and inhibited EL4-luc2 lymphoma proliferation. In our mechanism study, EMP was found to inhibit STAT3 phosphorylation in M2-polarized macrophages. These results suggest that EMP is effective in treating TAM-mediated tumor progression and metastasis.

  3. M2 macrophages activate WNT signaling pathway in epithelial cells: relevance in ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Jesús Cosín-Roger

    Full Text Available Macrophages, which exhibit great plasticity, are important components of the inflamed tissue and constitute an essential element of regenerative responses. Epithelial Wnt signalling is involved in mechanisms of proliferation and differentiation and expression of Wnt ligands by macrophages has been reported. We aim to determine whether the macrophage phenotype determines the expression of Wnt ligands, the influence of the macrophage phenotype in epithelial activation of Wnt signalling and the relevance of this pathway in ulcerative colitis. Human monocyte-derived macrophages and U937-derived macrophages were polarized towards M1 or M2 phenotypes and the expression of Wnt1 and Wnt3a was analyzed by qPCR. The effects of macrophages and the role of Wnt1 were analyzed on the expression of β-catenin, Tcf-4, c-Myc and markers of cell differentiation in a co-culture system with Caco-2 cells. Immunohistochemical staining of CD68, CD206, CD86, Wnt1, β-catenin and c-Myc were evaluated in the damaged and non-damaged mucosa of patients with UC. We also determined the mRNA expression of Lgr5 and c-Myc by qPCR and protein levels of β-catenin by western blot. Results show that M2, and no M1, activated the Wnt signaling pathway in co-culture epithelial cells through Wnt1 which impaired enterocyte differentiation. A significant increase in the number of CD206+ macrophages was observed in the damaged mucosa of chronic vs newly diagnosed patients. CD206 immunostaining co-localized with Wnt1 in the mucosa and these cells were associated with activation of canonical Wnt signalling pathway in epithelial cells and diminution of alkaline phosphatase activity. Our results show that M2 macrophages, and not M1, activate Wnt signalling pathways and decrease enterocyte differentiation in co-cultured epithelial cells. In the mucosa of UC patients, M2 macrophages increase with chronicity and are associated with activation of epithelial Wnt signalling and diminution in

  4. 183-W, M2 = 2.4 Yb:YAG Q -switched laser

    International Nuclear Information System (INIS)

    Honea, E.C.; Beach, R.J.; Mitchell, S.C.; Avizonis, P.V.

    1999-01-01

    We have fabricated a diode-array end-pumped Yb:YAG rod laser with output powers greater than 200thinspthinspW cw and 195thinspthinspW Q -switched at 5thinspthinspkHz. At an output power of 183thinspthinspW and a repetition rate of 5thinspthinspkHz, the beam quality was measured to be M 2 =2.4 . The laser design incorporates a hollow lens duct to concentrate the diode pump light for delivery to the end of the laser rod while maintaining access to the laser beam. This configuration provides increased flexibility for the resonator design and permits the use of birefringence compensation in the cavity to yield polarized output with increased efficiency. Using the recently described birefringence compensation method of Clarkson et al.thinspthinsp[in Conference on Lasers and Electro-Optics (Optical Society of America, Washington, D.C., 1998), paper CTuI3], we obtained 112thinspthinspW of cw power with a polarized beam of M 2 =3.2 . copyright 1999 Optical Society of America

  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. Dual role of YM1+ M2 macrophages in allergic lung inflammation

    NARCIS (Netherlands)

    Draijer, Christina; Robbe, Patricia; Boorsma, Carian E; Hylkema, Machteld N; Melgert, Barbro N

    2018-01-01

    Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation

  7. Machine-to-Machine networks: integration of M2M networks into companies' administrative networks

    OpenAIRE

    Pointereau, Romain

    2013-01-01

    This analysis will address the technical, economic and regulatory aspects and will identify the position taken by the various market actors. Integration of M2M Networks into Companies' Administrative Networks. Integración de redes M2M en redes administrativas de las empresas. Integració de xarxes M2M en xarxes administratives de les empreses.

  8. Structural impact of creep in tungsten monoblock divertor target at 20 MW/m2

    Directory of Open Access Journals (Sweden)

    Muyuan Li

    2018-01-01

    Full Text Available In order to increase erosion lifetime of the divertor target, in the 2nd design phase of R&D work package ‘Divertor’ for European DEMO, armor thickness of tungsten monoblock divertor target is increased from 5 mm to 8 mm. By increasing armor thickness, surface temperature increases nearly linearly, which makes effect of creep no longer negligible at slow transients of 20 MW/m2. In this work, structural impact of creep in tungsten monoblock divertor target is for the first time quantitatively analyzed with the aid of finite element method. The numerical simulations have revealed that creep results in an increase of inelastic strain accumulation. With increasing armor thickness, tensile surface stress along x-axis (the longer edge at the plasma-facing surface of tungsten monoblock reduces, while surface stress along z-axis (axial direction of the cooling tube changes from tensile to compressive. Creep will accelerate this change. With increasing grain size, creep strain accumulation at loading surface increases due to higher creep rates, while plastic strain accumulation decreases. Creep can mitigate the risk of deep cracking by reducing the driving force for crack opening, and has a positive impact for preventing the contact between the upper parts of neighboring monoblocks in high heat flux tests.

  9. 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

    Science.gov (United States)

    Liu, Chiu-Shong; Huang, Chiu-Ching; Lin, Wen-Yuan; Chiang, Jen-Huai; Lin, Cheng-Chieh; Li, Tsai-Chung

    2015-01-01

    Background 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. Methods 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. Results 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 HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c HbA1c of 6.0%–6.9%. Conclusions 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 HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy. PMID:26098901

  10. The mutual dependence of M1 fertility and M2 mutations in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1982-01-01

    The mutual dependence of M 1 fertility and M 2 mutations in rice was studied after treatment with gamma rays and EMS. The frequency of chlorophyll mutations increased with decrease in seed fertility when M 1 ears were selected at random. However, at the lowest fertility class the mutation frequency was low. This reduction is attributed to the elimination of mutants in the high sterility class. The mutation yield can therefore be significantly enhanced by selecting M 1 ears of low fertility. The segregation ratio of mutants increased as fertility decreased. Mutation spectrum was however not influenced by M 1 fertility. This makes selection for fertility quite ineffective in altering the mutation spectrum. (author)

  11. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

    Science.gov (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

    2017-08-01

    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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; Schulze, Tobias

    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 (S1P 1-5 ) 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 S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . 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.

  14. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  15. Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms

    Science.gov (United States)

    Rőszer, Tamás

    2015-01-01

    The alternatively activated or M2 macrophages are immune cells with high phenotypic heterogeneity and are governing functions at the interface of immunity, tissue homeostasis, metabolism, and endocrine signaling. Today the M2 macrophages are identified based on the expression pattern of a set of M2 markers. These markers are transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors with diverse and often yet unexplored functions. This review discusses whether these M2 markers can be reliably used to identify M2 macrophages and define their functional subdivisions. Also, it provides an update on the novel signals of the tissue environment and the neuroendocrine system which shape the M2 activation. The possible evolutionary roots of the M2 macrophage functions are also discussed. PMID:26089604

  16. Reexamination of M2,3 atomic level widths and L1M2,3 transition energies of elements 69≤Z≤95

    Science.gov (United States)

    Fennane, K.; Berset, M.; Dousse, J.-Cl.; Hoszowska, J.; Raboud, P.-A.; Campbell, J. L.

    2013-11-01

    We report on high-resolution measurements of the photoinduced L1M2 and L1M3 x-ray emission lines of 69Tm, 70Yb, 71Lu, 73Ta, 74W, 75Re, 77Ir, 81Tl, 83Bi, and 95Am. From the linewidths of the measured transitions an accurate set of M2 and M3 level widths is determined assuming for the L1 level widths the values reported by Raboud [P.-A. Raboud et al., Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.65.022512 65, 022512 (2002)]. Furthermore, the present experimental M2,3 data set is extended to 80Hg, 90Th, and 92U, using former L1M2,3 high-resolution x-ray emission spectroscopy measurements performed by our group. A detailed comparison of the M2 and M3 level widths determined in the present work with those recommended by Campbell and Papp [J. L. Campbell and T. Papp, At. Data Nucl. Data TablesADNDAT0092-640X10.1006/adnd.2000.0848 77, 1 (2001)] and other available experimental data as well as theoretical predictions is done. The observed abrupt changes of the M2,3 level widths versus atomic number Z can be explained satisfactorily by the cutoffs and onsets of the M2M4N1, respectively M3M4N3,4,5 and M3M5N2,3 Coster-Kronig transitions deduced from the semiempirical (Z+1) approximation. As a spin-off result of this study, precise L1M2 and L1M3 transition energies are obtained for the investigated elements. A very good agreement with transition energies calculated within the many-body perturbation theory is found.

  17. 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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    We have imaged the bipolar planetary nebula M2-9 using SOFIA's FORCAST instrument in six wavelength bands between 6.6 and 37.1 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.

  19. Posttranslational Modifications of Pyruvate Kinase M2: Tweaks that Benefit Cancer

    Directory of Open Access Journals (Sweden)

    Gopinath Prakasam

    2018-02-01

    Full Text Available Cancer cells rewire metabolism to meet biosynthetic and energetic demands. The characteristic increase in glycolysis, i.e., Warburg effect, now considered as a hallmark, supports cancer in various ways. To attain such metabolic reshuffle, cancer cells preferentially re-express the M2 isoform of pyruvate kinase (PKM2, M2-PK and alter its quaternary structure to generate less-active PKM2 dimers. The relatively inactive dimers cause the accumulation of glycolytic intermediates that are redirected into anabolic pathways. In addition, dimeric PKM2 also benefits cancer cells through various non-glycolytic moonlight functions, such as gene transcription, protein kinase activity, and redox balance. A large body of data have shown that several distinct posttranslation modifications (PTMs regulate PKM2 in a way that benefits cancer growth, e.g., formation of PKM2 dimers. This review discusses the recent advancements in our understanding of various PTMs and the benefits they impart to the sustenance of cancer. Understanding the PTMs in PKM2 is crucial to assess their therapeutic potential and to design novel anticancer strategies.

  20. Chemotherapy alters monocyte differentiation to favor generation of cancer-supporting M2 macrophages in the tumor microenvironment

    NARCIS (Netherlands)

    Dijkgraaf, Eveline M.; Heusinkveld, Moniek; Tummers, Bart; Vogelpoel, Lisa T. C.; Goedemans, Renske; Jha, Veena; Nortier, Johan W. R.; Welters, Marij J. P.; Kroep, Judith R.; van der Burg, Sjoerd H.

    2013-01-01

    Current therapy of gynecologic malignancies consists of platinum-containing chemotherapy. Resistance to therapy is associated with increased levels of interleukin (IL)-6 and prostaglandin E2 (PGE(2)), 2 inflammatory mediators known to skew differentiation of monocytes to tumor-promoting M2

  1. IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

    Directory of Open Access Journals (Sweden)

    Zijian Xie

    2012-03-01

    Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

  2. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

    Science.gov (United States)

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

    2016-01-01

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

  3. Solar thermal barometer. More than 2 million m2 installed in 2005

    International Nuclear Information System (INIS)

    Anon.

    2006-01-01

    With 22,8% growth, the european union solar thermal market (glazed, vacuum and unglazed collectors) has passed the 2 million m 2 benchmark corresponding to installed capacity of approximately 1450 MWth. This growth can be explained by the very good performance of the three leading EU solar thermal markets: Germany, Austria and Greece and the increase in importance of the French and Spanish markets. Statistical data are provided for the european union on the annually installed surfaces, breakdown by technologies of the solar thermal market, the solar thermal capacity in operation, the representative companies of the thermal solar sector and a comparison of current trend with the white book objectives. (A.L.B.)

  4. Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages

    Science.gov (United States)

    2014-01-01

    Introduction The mortality of rhabdomyolysis-induced acute kidney injury (AKI) is still high, as there is no effective therapy. It has been shown that bone marrow-derived mesenchymal stem cells (MSCs) can induce M2 macrophages, which mediate MSC protection in other experimental inflammation-related organ injury. This study was designed to investigate the protective effects of macrophage activation in MSC therapy of rhabdomyolysis-induced AKI. Methods MSCs were injected into glycerol-induced rhabdomyolysis mice. Renal injury was evaluated using the serum creatinine, urea nitrogen, renal pathology and acute tubular necrosis score. The distribution of MSCs was detected using two-photon fluorescence confocal imaging. Immunofluorescence of anti-F4/80 and anti-CD206 was performed to determine macrophages and M2 macrophages in the tissues of the kidney, and M2 macrophage infiltration was also evaluated using western blotting analyses. After depletion of macrophages using clodronate liposomes at the phase of kidney repair, renal injury was re-evaluated. RAW 264.7 macrophages were incubated with lipopolysaccharide and co-cultured with MSCs and subsequently visualised using immunofluorescence staining and flow cytometry analysis. Finally, disparate phenotype macrophages, including normal macrophages (M0), lipopolysaccharide-stimulated macrophages (M1), and MSC-co-cultured macrophages (M2), were infused into mice with AKI, which were pre-treated with liposomal clodronate. Results In vivo infusion of MSCs protected AKI mice from renal function impairment and severe tubular injury, which was accompanied by a time-dependent increase in CD206-positive M2 macrophage infiltration. In addition, depleting macrophages with clodronate delayed restoration of AKI. In vitro, macrophages co-cultured with MSCs acquired an anti-inflammatory M2 phenotype, which was characterised by an increased expression of CD206 and the secretory cytokine interleukin (IL)-10. The concentrations of IL-10, IL

  5. Distributed Energy-Efficient Topology Control Algorithm in Home M2M Networks

    OpenAIRE

    Lee, Chao-Yang; Yang, Chu-Sing

    2012-01-01

    Because machine-to-machine (M2M) technology enables machines to communicate with each other without human intervention, it could play a big role in sensor network systems. Through wireless sensor network (WSN) gateways, various information can be collected by sensors for M2M systems. For home M2M networks, this study proposes a distributed energy-efficient topology control algorithm for both topology construction and topology maintenance. Topology control is an effective method of enhancing e...

  6. 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...... 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...

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

    International Nuclear Information System (INIS)

    Mori, Kazumasa; Hiroi, Miki; Shimada, Jun; Ohmori, Yoshihiro

    2011-01-01

    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

  8. 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.

  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

    1998-12-31

    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. 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.

  11. 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.

  12. Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages.

    Science.gov (United States)

    Bellora, Francesca; Dondero, Alessandra; Corrias, Maria Valeria; Casu, Beatrice; Regis, Stefano; Caliendo, Fabio; Moretta, Alessandro; Cazzola, Mario; Elena, Chiara; Vinti, Luciana; Locatelli, Franco; Bottino, Cristina; Castriconi, Roberta

    2017-08-15

    Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells. In NB, neither drug reduced the expression of ligands for activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD-L2, molecules that might limit NK cell function. Interestingly, TKIs modulated the chemokine receptor repertoire of immune cells. Acting at the transcriptional level, they increased the surface expression of CXCR4, an effect observed also in NK cells and monocytes of patients receiving imatinib for chronic myeloid leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1 (in monocytes). Monocytes also decreased the expression of M-CSFR, and low numbers of cells underwent differentiation toward macrophages. M0 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional characteristics. Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted by TLR engagement, and M1-oriented macrophages fully activated autologous NK cells. Our results contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at facilitating antitumor immune responses. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. Coupling of g proteins to reconstituted monomers and tetramers of the M2 muscarinic receptor.

    Science.gov (United States)

    Redka, Dar'ya S; Morizumi, Takefumi; Elmslie, Gwendolynne; Paranthaman, Pranavan; Shivnaraine, Rabindra V; Ellis, John; Ernst, Oliver P; Wells, James W

    2014-08-29

    G protein-coupled receptors can be reconstituted as monomers in nanodiscs and as tetramers in liposomes. When reconstituted with G proteins, both forms enable an allosteric interaction between agonists and guanylyl nucleotides. Both forms, therefore, are candidates for the complex that controls signaling at the level of the receptor. To identify the biologically relevant form, reconstituted monomers and tetramers of the purified M2 muscarinic receptor were compared with muscarinic receptors in sarcolemmal membranes for the effect of guanosine 5'-[β,γ-imido]triphosphate (GMP-PNP) on the inhibition of N-[(3)H]methylscopolamine by the agonist oxotremorine-M. With monomers, a stepwise increase in the concentration of GMP-PNP effected a lateral, rightward shift in the semilogarithmic binding profile (i.e. a progressive decrease in the apparent affinity of oxotremorine-M). With tetramers and receptors in sarcolemmal membranes, GMP-PNP effected a vertical, upward shift (i.e. an apparent redistribution of sites from a state of high affinity to one of low affinity with no change in affinity per se). The data were analyzed in terms of a mechanistic scheme based on a ligand-regulated equilibrium between uncoupled and G protein-coupled receptors (the "ternary complex model"). The model predicts a rightward shift in the presence of GMP-PNP and could not account for the effects at tetramers in vesicles or receptors in sarcolemmal membranes. Monomers present a special case of the model in which agonists and guanylyl nucleotides interact within a complex that is both constitutive and stable. The results favor oligomers of the M2 receptor over monomers as the biologically relevant state for coupling to G proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Models for financial crisis detection in Indonesia based on M1, M2 per foreign exchange reverse, and M2 multiplier indicators

    Science.gov (United States)

    Sugiyanto; Zukhronah, Etik; Pratiwi, Esteti Sophia

    2017-12-01

    Indonesia has been hit by financial crisis in the middle of 1997. The financial crisis that has occurred gives a severe impact to the economy of Indonesia resulting the needs for a detection system of financial crisis. Crisis can be detected based on several indicators such as M1, M2 per foreign exchange reserves, and M2 multiplier. These three indicators can affect the exchange rate stability and may further affect the financial stability so that it can be one of the causes of the financial crisis. This research aims to determine the appropriate model that can detect the financial crisis in Indonesia. Markov switching is an alternative model that can be approach and used often for detecting financial crisis. We can determine the combination of volatility and Markov switching model with AR and volatility model are determined first. The results of this research are that M1 can be modelled by SWARCH (3, 1) while M2 per foreign research exchange reserves and M2 multiplier can be modelled by SWARCH(3,2).

  15. 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 nearest...

  16. Establishing a Research Center: The Minority Male Community College Collaborative (M2C3)

    Science.gov (United States)

    Wood, J. Luke; Urias, Marissa Vasquez; Harris, Frank, III

    2016-01-01

    This chapter describes the establishment of the Minority Male Community College Collaborative (M2C3), a research and practice center at San Diego State University. M2C3 partners with community colleges across the United States to enhance access, achievement, and success among men of color. This chapter begins with a description of the national…

  17. Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein.

    Directory of Open Access Journals (Sweden)

    Marie-Lise Blondot

    Full Text Available Respiratory syncytial virus (RSV protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177 core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177, as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.

  18. M2- and M5-branes in E11 current algebra formulation of M-theory

    Science.gov (United States)

    Shiba, Shotaro; Sugawara, Hirotaka

    2018-03-01

    Equations of motion for M2- and M5-branes are written down in the E11 current algebra formulation of M-theory. These branes correspond to currents of the second and the fifth rank antisymmetric tensors in the E11 representation, whereas the electric and magnetic fields (coupled to M2- and M5-branes) correspond to currents of the third and the sixth rank antisymmetric tensors, respectively. We show that these equations of motion have solutions in terms of the coordinates on M2- and M5-branes. We also discuss the geometric equations, and show that there are static solutions when M2- or M5-brane exists alone and also when M5-brane wraps around M2-brane. This situation is realized because our Einstein-like equation contains an extra term which can be interpreted as gravitational energy contributing to the curvature, thus avoiding the usual intersection rule.

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

    DEFF Research Database (Denmark)

    Madueño, Germán Corrales

    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...... as the preferable solution for M2M, no mechanisms are in place to guarantee reliable M2M access. Contrary to mainstream solutions that focus on preventing overload, we introduce mechanisms to provide reliable M2M service. We also investigate what cellular networks can do about upcoming smart metering traffic...

  20. 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

    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......Managing access to and protecting resources is one of the important aspect in managing security, especially in a distributed computing system such as Machine-to-Machine (M2M). One such platform known as the M2M local cloud platform, referring to BETaaS architecture [1], which conceptually consists...... 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...

  1. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.

    Directory of Open Access Journals (Sweden)

    Al Shaimaa Hasan

    Full Text Available Cardiosphere-derived cells (CDCs, one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1 into a regulatory anti-inflammatory phenotype (M2. Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages, but decreased the expression of CD86 (a marker for M1 macrophages 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.

  2. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

    Science.gov (United States)

    Hasan, Al Shaimaa; Luo, Lan; Yan, Chen; Zhang, Tian-Xia; Urata, Yoshishige; Goto, Shinji; Mangoura, Safwat A.; Abdel-Raheem, Mahmoud H.; Zhang, Shouhua; Li, Tao-Sheng

    2016-01-01

    Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair. PMID:27764217

  3. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

    Science.gov (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh

    2018-02-06

    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  4. Nanomaterial Containing Wall Paints Can Increase Radon Concentration in Houses Located in Radon Prone Areas Haghani M.2 , Mortazavi S. M. J.1, 2*, Faghihi R.3, Mehdizadeh S.3, Moradgholi J.4, Darvish L.5, Fathi-Pour E.5, Ansari L.5, Ghanbar-pour M. R.3 1The Center for Radiological Research, Shiraz University of Medical Sciences, Shiraz, Iran 2Department of Med

    Directory of Open Access Journals (Sweden)

    Haghani M.

    2013-09-01

    Full Text Available Background: Nowadays, extensive technological advancements have made it possible to use nanopaints which show exciting properties. In IR Iran excessive radon levels (up to 3700 Bq m–3 have been reported in homes located in radon prone areas. Over the past decades, concerns have been raised about the risk posed by residential radon exposure. Objective: This study aims at investigating the effect of using nanomaterial containing wall paints on radon concentration in homes. Methods: Two wooden model houses were used in this study. Soil samples from Ramsar high background radiation areas were used for simulating the situation of a typical house in radon-prone areas. Conventional water-soluble wall paint was used for painting the walls of the 1st house model; while the 2nd house model was painted with the same wall paint with montmorillonite nanoclay. Results: Three days after sealing the house models, radon level was measured by using a portable radon survey meter. The mean radon level inside the 1st house model (conventional paint was 515.3 ± 17.8 Bq/m3 while the mean radon concentration in the 2nd house model (nano-painted house model was 570.8 ± 18.5 Bq/m3. The difference between these means was statistically signifcant (P<0.001. Conclusion: To the best of our knowledge, this study is the frst investigation on the effect of nano-material containing wall paints on indoor radon concentrations. It can be concluded that nano-material-containing wall paints should not be used in houses with wooden walls located in radon prone areas. Although the mechanism of this effect is not clearly known, decreased porosity in nano-paints might be a key factor in increasing the radon concentration in homes.

  5. 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

  6. The Predictive Factors for Diabetic Remission in Chinese Patients with BMI > 30 kg/m2 and BMI < 30 kg/m2 Are Different.

    Science.gov (United States)

    Liang, Hui; Cao, Qing; Liu, Huan; Guan, Wei; Wong, Claudia; Tong, Daniel

    2018-01-15

    Roux-en-Y gastric bypass has been proven to be beneficial for patients with obesity and type 2 diabetes mellitus (T2DM). In less-obese patient (BMI 30-35 kg/m 2 ), surgical treatment is indicated when medication fails to control the T2DM. Asian develops diabetes at a lower BMI. For lower-BMI patients, the rate of diabetes amelioration varies significantly with patients of higher BMI after surgical treatment. The factors that contribute to the post-operative diabetes response rate in lower-BMI patients have not been elucidated. Between 2010 and 2014, a total of 144 patients who underwent gastric bypass for the treatment of T2DM were included for study. Patients were divided into two groups for subgroup analysis, namely BMI > 30 kg/m 2 and BMI BMI group (BMI > 30 kg/m 2 ) was 80% (n = 90) whereas for the lower BMI (BMI BMI group, low HbA1c and high fasting C-peptide are predictive factors whereas for lower-BMI group, along with elevated C-peptide level, disease duration is the positive predictive factor for DM remission. Patients with BMI > 30 kg/m 2 and those with BMI BMI patients while duration of diabetes is for high-low-BMI patients. C-peptide is a predictor of remission in both groups. Further large-scale studies are required to define the predictors of diabetes remission after gastric bypass in low- and high-BMI patients.

  7. 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.

  8. Phosphorylation of Human Metapneumovirus M2-1 Protein Upregulates Viral Replication and Pathogenesis.

    Science.gov (United States)

    Cai, Hui; Zhang, Yu; Lu, Mijia; Liang, Xueya; Jennings, Ryan; Niewiesk, Stefan; Li, Jianrong

    2016-08-15

    Human metapneumovirus (hMPV) is a major causative agent of upper- and lower-respiratory-tract infections in infants, the elderly, and immunocompromised individuals worldwide. Like all pneumoviruses, hMPV encodes the zinc binding protein M2-1, which plays important regulatory roles in RNA synthesis. The M2-1 protein is phosphorylated, but the specific role(s) of the phosphorylation in viral replication and pathogenesis remains unknown. In this study, we found that hMPV M2-1 is phosphorylated at amino acid residues S57 and S60. Subsequent mutagenesis found that phosphorylation is not essential for zinc binding activity and oligomerization, whereas inhibition of zinc binding activity abolished the phosphorylation and oligomerization of the M2-1 protein. Using a reverse genetics system, recombinant hMPVs (rhMPVs) lacking either one or both phosphorylation sites in the M2-1 protein were recovered. These recombinant viruses had a significant decrease in both genomic RNA replication and mRNA transcription. In addition, these recombinant viruses were highly attenuated in cell culture and cotton rats. Importantly, rhMPVs lacking phosphorylation in the M2-1 protein triggered high levels of neutralizing antibody and provided complete protection against challenge with wild-type hMPV. Collectively, these data demonstrated that phosphorylation of the M2-1 protein upregulates hMPV RNA synthesis, replication, and pathogenesis in vivo The pneumoviruses include many important human and animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the leading causes of acute respiratory tract infection in infants and children. Currently, there is no antiviral or vaccine to combat these diseases. All known pneumoviruses encode a zinc binding protein, M2-1, which is a transcriptional antitermination factor. In this work, we found that phosphorylation of M2-1 is essential for virus

  9. Comparison of 14 MeV isomer production of 178m2Hf and 179m2Hf using Feshbach-Kerman-Koonin and exciton preequilibrium models

    International Nuclear Information System (INIS)

    Chadwick, M.B.; Young, P.G.

    1993-01-01

    The 178m2 Hf(16+) isomeric state has a 31-yr half life and could pose serious radioactive problems in nuclear fusion reactors if its production in 14 MeV neutron-induced reactions is significant. We present statistical/preequilibrium model calculations for the production of this isomer in the 179 Hf(n, 2n) 178m2 Hf reaction, as well as the 25-days 12.5 - isomer in the 179 Hf(n,n') 179m2 Hf reaction, using two different preequilibrium models: the exciton model and the Feshbach-Kerman-Koonin (FKK) theory. Our calculations which use the exciton model agree well with measurements, but those with the FKK theory underestimate measurements. Our calculations axe the first to probe angular momentum transfer effects in the FKK theory and suggest that, as it is presently applied, high spin-transfer reactions are underestimated. We suggest modifications to the FKK statistical averaging procedure which may result in an improved agreement with experiment

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

    International Nuclear Information System (INIS)

    Qin, Tian; Wang, Chenlong; Chen, Xuewei; Duan, Chenfan; Zhang, Xiaoyan; Zhang, Jing; Chai, Hongyan; Tang, Tian; Chen, Honglei; Yue, Jiang; Li, Ying; Yang, Jing

    2015-01-01

    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

  11. 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

  12. 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...

  13. miR-434-3p and DNA hypomethylation co-regulate eIF5A1 to increase AChRs and to improve plasticity in SCT rat skeletal muscle.

    Science.gov (United States)

    Shang, Fei-Fei; Xia, Qing-Jie; Liu, Wei; Xia, Lei; Qian, Bao-Jiang; You, Ling; He, Mu; Yang, Jin-Liang; Wang, Ting-Hua

    2016-03-11

    Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

  14. An allostatic mechanism for M2 pyruvate kinase as an amino-acid sensor.

    Science.gov (United States)

    Yuan, Meng; McNae, Iain W; Chen, Yiyuan; Blackburn, Elizabeth A; Wear, Martin A; Michels, Paul A M; Fothergill-Gilmore, Linda A; Hupp, Ted; Walkinshaw, Malcolm D

    2018-05-10

    We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer-monomer dissociation K d is estimated to be ~0.9 µM with a slow dissociation rate (t 1/2 ~ 15 min). X-ray structures of M2PYK complexes with alanine, phenylalanine, and tryptophan show the M2PYK locked in an inactive T-state conformation, while activators lock the M2PYK tetramer in the active R-state conformation. Amino-acid binding in the allosteric pocket triggers rigid body rotations (11°) stabilising either T or R-states. The opposing inhibitory and activating effects of the non-essential amino acids serine and alanine suggest that M2PYK could act as a rapid-response nutrient sensor to rebalance cellular metabolism. This competition at a single allosteric site between activators and inhibitors provides a novel regulatory mechanism by which M2PYK activity is finely tuned by the relative (but not absolute) concentrations of activator and inhibitor amino acids. Such 'allostatic' regulation may be important in metabolic reprogramming and influencing cell fate. ©2018 The Author(s).

  15. 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)

  16. Detailed profile of m=2 islands with TVTS on JFT-2M

    International Nuclear Information System (INIS)

    Yamauchi, T.; Grek, B.; Hoshino, K.; Le Blanc, B.; Johnson, D.; Felt, J.; Shiina, T.; Kurita, G.; Ishige, Y.; Kozawa, H.

    1996-01-01

    The detailed electron temperature profile (spatial resolution: 0.86 cm) of a low density JFT-2M plasma is measured with the TV Thomson scattering system (TVTS). Flat profiles showing the electron temperature shapes of m=2/n=1 islands are presented, which are in contrast to that without islands. On the other hand, the m=2/n=1 islands are effectively suppressed with local ECRH heating. (orig.)

  17. Excess circulating alternatively activated myeloid (M2 cells accelerate ALS progression while inhibiting experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Ilan Vaknin

    Full Text Available Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs, representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.We tested this working hypothesis in amyotrophic lateral sclerosis (ALS and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2 cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1 mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE, which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS, revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/LowHLA-DR(-CD33(+ compared to controls.Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might

  18. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    Science.gov (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA1c and other predictors of increasing BMISDS.

    Science.gov (United States)

    Birkebaek, N H; Kahlert, J; Bjarnason, R; Drivvoll, A K; Johansen, A; Konradsdottir, E; Pundziute-Lyckå, A; Samuelsson, U; Skrivarhaug, T; Svensson, J

    2018-05-21

    Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A 1c (HbA 1c ), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. Totally, 11 025 children (48% females) (30 994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA 1c , 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA 1c and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P < .001). Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA 1c , long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA 1c. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Angela M Liu

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

  1. M2 Macrophages Play Critical Roles in Progression of Inflammatory Liver Disease in Hepatitis C Virus Transgenic Mice.

    Science.gov (United States)

    Ohtsuki, Takahiro; Kimura, Kiminori; Tokunaga, Yuko; Tsukiyama-Kohara, Kyoko; Tateno, Chise; Hayashi, Yukiko; Hishima, Tsunekazu; Kohara, Michinori

    2016-01-01

    Macrophages in liver tissue are widely defined as important inflammatory cells in chronic viral hepatitis due to their proinflammatory activity. We reported previously that interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) play significant roles in causing chronic hepatitis in hepatitis C virus (HCV) transgenic mice (S. Sekiguchi et al., PLoS One 7:e51656, 2012, http://dx.doi.org/10.1371/journal.pone.0051656). In addition, we showed that recombinant vaccinia viruses expressing an HCV nonstructural protein (rVV-N25) could protect against the progression of chronic hepatitis by suppression of macrophage activation. Here, we focus on the role of macrophages in liver disease progression in HCV transgenic mice and examine characteristic features of macrophages following rVV-N25 treatment. The number of CD11b(+) F4/80(+) CD11c(-) CD206(+) (M2) macrophages in the liver of HCV transgenic mice was notably increased compared to that of age-matched control mice. These M2 macrophages in the liver produced elevated levels of IL-6 and TNF-α. rVV-N25 infection suppressed the number and activation of M2 macrophages in liver tissue. These results suggested that inflammatory cytokines produced by M2-like macrophages contribute to the induction of chronic liver inflammation in HCV transgenic mice. Moreover, the therapeutic effect of rVV-N25 might be induced by the suppression of the number and activation of hepatic macrophages. HCV causes persistent infections that can lead to chronic liver diseases, liver fibrosis, and hepatocellular carcinoma; the search for an HCV curative is the focus of ongoing research. Recently, effective anti-HCV drugs have been developed; however, vaccine development still is required for the prevention and therapy of infection by this virus. We demonstrate here that M2 macrophages are important for the pathogenesis of HCV-caused liver diseases and additionally show that M2 macrophages contribute to the therapeutic mechanism observed following r

  2. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

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

  3. A Corticocortical Circuit Directly Links Retrosplenial Cortex to M2 in the Mouse

    Science.gov (United States)

    Radulovic, Jelena

    2016-01-01

    Retrosplenial cortex (RSC) is a dorsomedial parietal area involved in a range of cognitive functions, including episodic memory, navigation, and spatial memory. Anatomically, the RSC receives inputs from dorsal hippocampal networks and in turn projects to medial neocortical areas. A particularly prominent projection extends rostrally to the posterior secondary motor cortex (M2), suggesting a functional corticocortical link from the RSC to M2 and thus a bridge between hippocampal and neocortical networks involved in mnemonic and sensorimotor aspects of navigation. We investigated the cellular connectivity in this RSC→M2 projection in the mouse using optogenetic photostimulation, retrograde labeling, and electrophysiology. Axons from RSC formed monosynaptic excitatory connections onto M2 pyramidal neurons across layers and projection classes, including corticocortical/intratelencephalic neurons (reciprocally and callosally projecting) in layers 2–6, pyramidal tract neurons (corticocollicular, corticopontine) in layer 5B, and, to a lesser extent, corticothalamic neurons in layer 6. In addition to these direct connections, disynaptic connections were made via posterior parietal cortex (RSC→PPC→M2) and anteromedial thalamus (RSC→AM→M2). In the reverse direction, axons from M2 monosynaptically excited M2-projecting corticocortical neurons in the RSC, especially in the superficial layers of the dysgranular region. These findings establish an excitatory RSC→M2 corticocortical circuit that engages diverse types of excitatory projection neurons in the downstream area, suggesting a basis for direct communication from dorsal hippocampal networks involved in spatial memory and navigation to neocortical networks involved in diverse aspects of sensorimotor integration and motor control. SIGNIFICANCE STATEMENT Corticocortical pathways interconnect cortical areas extensively, but the cellular connectivity in these pathways remains largely uncharacterized. Here, we

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

    Science.gov (United States)

    Takeda, Hiroshi; Hori, Hiroyuki; Endo, Yaeta

    2002-01-01

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

  5. 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.

  6. Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor

    Science.gov (United States)

    Wan, Min; Zhang, Wenhua; Tian, Yangli; Xu, Chanjuan; Xu, Tao; Liu, Jianfeng; Zhang, Rongying

    2015-01-01

    Endocytosis and postendocytic sorting of G-protein-coupled receptors (GPCRs) is important for the regulation of both their cell surface density and signaling profile. Unlike the mechanisms of clathrin-dependent endocytosis (CDE), the mechanisms underlying the control of GPCR signaling by clathrin-independent endocytosis (CIE) remain largely unknown. Among the muscarinic acetylcholine receptors (mAChRs), the M4 mAChR undergoes CDE and recycling, whereas the M2 mAChR is internalized through CIE and targeted to lysosomes. Here we investigated the endocytosis and postendocytic trafficking of M2 mAChR based on a comparative analysis of the third cytoplasmic domain in M2 and M4 mAChRs. For the first time, we identified that the sequence 374KKKPPPS380 servers as a sorting signal for the clathrin-independent internalization of M2 mAChR. Switching 374KKKPPPS380 to the i3 loop of the M4 mAChR shifted the receptor into lysosomes through the CIE pathway; and therefore away from CDE and recycling. We also found another previously unidentified sequence that guides CDE of the M2 mAChR, 361VARKIVKMTKQPA373, which is normally masked in the presence of the downstream sequence 374KKKPPPS380. Taken together, our data indicate that endocytosis and postendocytic sorting of GPCRs that undergo CIE could be sequence-dependent. PMID:26094760

  7. Initial Search for Triggered Gamma Emission from {sup 178}Hf{sup m2} Using the YSU Miniball Array

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, J. J.; Burnett, J.; Drummond, T.; Lepak, J.; Propri, R.; Smith, D. [Youngstown State University, Department of Physics and Astronomy, Center for Photon-Induced Processes (United States); Karamian, S. A.; Adam, J. [Joint Institute for Nuclear Research (Russian Federation); Stedile, F. [Universitaet Stuttgart, Institut fuer Strahlenphysik (Germany); Agee, F. J. [Air Force Office of Scientific Research, AFOSR/NE (United States)

    2002-11-15

    Experiments with the long-lived, high-K isomer {sup 178}Hf{sup m2} have been recognized as intriguing tests of multi-quasiparticle state structures and their interactions with external radiation. A triggered release of the energy stored by this isomer, 2.5 MeV per nucleus or 1.2 GJ/gram, in the form of a gamma-ray burst might prove valuable for numerous applications. The observation of 'accelerated' decay of {sup 178}Hf{sup m2} during irradiation by 90-keV bremsstrahlung has already been reported, but with poor statistical accuracy due to the experimental approach. That approach employed single Ge detectors to seek increases in the areas of peaks at energies corresponding to transitions in the spontaneous decay of the isomer. The need for better quality data to confirm those results has motivated the development of improved detection concepts. One such concept was utilized here to perform an initial search for low-energy (<20 keV) triggered gamma emission from {sup 178}Hf{sup m2} using the YSU miniball detector array.

  8. Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

    Directory of Open Access Journals (Sweden)

    Laura Dugo

    2017-01-01

    Full Text Available Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

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

    International Nuclear Information System (INIS)

    Roosild, Tarmo P.; Castronovo, Samantha; Choe, Senyon

    2006-01-01

    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 + 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

  10. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

    Science.gov (United States)

    Li, Junjie; Xie, Jiangang; Liu, Shanshou; Li, Xiao; Zhang, Dongliang; Wang, Xianqi; Jiang, Jinquan; Hu, Wei; Zhang, Yuan; Jin, Boquan; Zhuang, Ran; Yin, Wen

    2018-04-25

    ADAR1 (adenosine deaminase acting on double-stranded RNA 1) is an RNA-editing enzyme that mediates adenosine-to-inosine RNA editing events, an important post-transcriptional modification mechanism that can alter the coding properties of mRNA or regulate microRNA biogenesis. ADAR1 also regulates the innate immune response. Here, we have demonstrated that ADAR1 expression increased in LPS-stimulated macrophages. Silencing ADAR1 by using small interfering RNA in macrophages resulted in the pronounced polarization of macrophages to M1, whereas ADAR1 overexpression promoted M2 polarization, which indicated that ADAR1 can inhibit macrophage hyperpolarization and prevent immune hyperactivity. The RNA-RNP immunoprecipitation binding assay demonstrated a direct interaction between ADAR1 and miR-21 precursor. Significant up-regulation in IL-10 and down-regulation in miR-21 were observed in ADAR1-overexpressing macrophages. We evaluated miR-21 target mRNAs and macrophage polarization signaling pathways and found that forkhead box protein O1 (Foxo1) was up-regulated in cells that overexpressed ADAR1. In a mouse allogeneic skin transplantation model, grafts in the ADAR1-overexpressed group survived longer and suffered less immune cell infiltration. In ADAR1-overexpressed recipients, splenic macrophages were significantly polarized to M2, and levels of sera IL-10 were markedly higher than those in the control group. In summary, ADAR1 modulates macrophage M2 polarization via the ADAR1-miR-21-Foxo1-IL-10 axis, thereby suppressing allogeneic graft rejection.-Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., Jiang, J., Hu, W., Zhang, Y., Jin, B., Zhuang, R., Yin, W. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

  11. 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...... represent an effective way to avoid access congestion and cell overload. In this paper, we propose a new strategy inspired by the classical Trunked Radio Systems (TRS), exploiting the Device-to-Device (D2D) connectivity between cellular users and Machine-Type Devices (MTDs). The aggregation of the locally...

  12. M2-F1 in flight being towed by a C-47

    Science.gov (United States)

    1964-01-01

    The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. 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. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. 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

  13. Comments on the Bagger-Lambert theory and multiple M2-branes

    International Nuclear Information System (INIS)

    Raamsdonk, Mark Van

    2008-01-01

    We study the SO(8) superconformal theory proposed recently by Bagger and Lambert as a possible worldvolume theory for multiple M2-branes. For their explicit example with gauge group SO(4), we rewrite the theory (originally formulated in terms of a three-algebra) as an ordinary SU(2) x SU(2) gauge theory with bifundamental matter. In this description, the parity invariance of the theory, required for a proper description of M2-branes, is clarified. We describe the subspace of scalar field configurations on which the potential vanishes, correcting an earlier claim. Finally, we point out, for general three-algebras, a difficulty in constructing the required set of superconformal primary operators which should be present in the correct theory describing multiple M2-branes.

  14. M2 FILTER FOR SPECKLE NOISE SUPPRESSION IN BREAST ULTRASOUND IMAGES

    Directory of Open Access Journals (Sweden)

    E.S. Samundeeswari

    2016-11-01

    Full Text Available Breast cancer, commonly found in women is a serious life threatening disease due to its invasive nature. Ultrasound (US imaging method plays an effective role in screening early detection and diagnosis of Breast cancer. Speckle noise generally affects medical ultrasound images and also causes a number of difficulties in identifying the Region of Interest. Suppressing speckle noise is a challenging task as it destroys fine edge details. No specific filter is designed yet to get a noise free BUS image that is contaminated by speckle noise. In this paper M2 filter, a novel hybrid of linear and nonlinear filter is proposed and compared to other spatial filters with 3×3 kernel size. The performance of the proposed M2 filter is measured by statistical quantity parameters like MSE, PSNR and SSI. The experimental analysis clearly shows that the proposed M2 filter outperforms better than other spatial filters by 2% high PSNR values with regards to speckle suppression.

  15. M2IRAGE: Management of measurements during radiological interventions geographically assisted in the environment

    International Nuclear Information System (INIS)

    Gerphagnon, O.; Roche, H.; Lelache, H.; Guelin, M.; Fauquant, J.M.; Kacenelen, Y.; Armand, Y.

    2010-01-01

    This report presents the M 2 IRAGE software, a data processing tool designed to share radioactivity measurements and to give a schematised view of a radiological situation and of its evolution, while respecting different legal frameworks, notably the obligation to produce a radiological measurement programme. After a simplified recall of the crisis management organisation, the authors describe the M 2 IRAGE software and hardware architecture, the functions of its main modules (presentation of radioprotection information during field intervention, field mission management, data browsing, and data transmission to field teams). While giving some display examples, the authors describe how an event is managed and processed by this tool: event creation, measurement acquisition, aid to decision, team management. They report and discuss the results of a national exercise which took place in September 2009 in Saclay with a prototype version of M 2 IRAGE

  16. Treadmill desks: A 1-year prospective trial.

    Science.gov (United States)

    Koepp, Gabriel A; Manohar, Chinmay U; McCrady-Spitzer, Shelly K; Ben-Ner, Avner; Hamann, Darla J; Runge, Carlisle F; Levine, James A

    2013-04-01

    Sedentariness is associated with weight gain and obesity. A treadmill desk is the combination of a standing desk and a treadmill that allow employees to work while walking at low speed. The hypothesis was that a 1-year intervention with treadmill desks is associated with an increase in employee daily physical activity (summation of all activity per minute) and a decrease in daily sedentary time (zero activity). Employees (n = 36; 25 women, 11 men) with sedentary jobs (87 ± 27 kg, BMI 29 ± 7 kg/m(2) , n = 10 Lean BMI 30 kg/m(2) ) volunteered to have their traditional desk replaced with a treadmill desk to promote physical activity for 1 year. Daily physical activity (using accelerometers), work performance, body composition, and blood variables were measured at Baseline and 6 and 12 months after the treadmill desk intervention. Subjects who used the treadmill desk increased daily physical activity from baseline 3,353 ± 1,802 activity units (AU)/day to, at 6 months, 4,460 ± 2,376 AU/day (P office workers without affecting work performance. Copyright © 2012 The Obesity Society.

  17. Control software architecture and operating modes of the Model M-2 maintenance system

    Energy Technology Data Exchange (ETDEWEB)

    Satterlee, P.E. Jr.; Martin, H.L.; Herndon, J.N.

    1984-04-01

    The Model M-2 maintenance system is the first completely digitally controlled servomanipulator. The M-2 system allows dexterous operations to be performed remotely using bilateral force-reflecting master/slave techniques, and its integrated operator interface takes advantage of touch-screen-driven menus to allow selection of all possible operating modes. The control system hardware for this system has been described previously. This paper describes the architecture of the overall control system. The system's various modes of operation are identified, the software implementation of each is described, system diagnostic routines are described, and highlights of the computer-augmented operator interface are discussed. 3 references, 5 figures.

  18. Modelling the enigmatic Late Pliocene Glacial Event - Marine Isotope Stage M2

    Science.gov (United States)

    Dolan, Aisling M.; Haywood, Alan M.; Hunter, Stephen J.; Tindall, Julia C.; Dowsett, Harry J.; Hill, Daniel J.; Pickering, Steven J.

    2015-01-01

    The Pliocene Epoch (5.2 to 2.58 Ma) has often been targeted to investigate the nature of warm climates. However, climate records for the Pliocene exhibit significant variability and show intervals that apparently experienced a cooler than modern climate. Marine Isotope Stage (MIS) M2 (~ 3.3 Ma) is a globally recognisable cooling event that disturbs an otherwise relatively (compared to present-day) warm background climate state. It remains unclear whether this event corresponds to significant ice sheet build-up in the Northern and Southern Hemisphere. Estimates of sea level for this interval vary, and range from modern values to estimates of 65 m sea level fall with respect to present day. Here we implement plausible M2 ice sheet configurations into a coupled atmosphere–ocean climate model to test the hypothesis that larger-than-modern ice sheet configurations may have existed at M2. Climate model results are compared with proxy climate data available for M2 to assess the plausibility of each ice sheet configuration. Whilst the outcomes of our data/model comparisons are not in all cases straight forward to interpret, there is little indication that results from model simulations in which significant ice masses have been prescribed in the Northern Hemisphere are incompatible with proxy data from the North Atlantic, Northeast Arctic Russia, North Africa and the Southern Ocean. Therefore, our model results do not preclude the possibility of the existence of larger ice masses during M2 in the Northern or Southern Hemisphere. Specifically they are not able to discount the possibility of significant ice masses in the Northern Hemisphere during the M2 event, consistent with a global sea-level fall of between 40 m and 60 m. This study highlights the general need for more focused and coordinated data generation in the future to improve the coverage and consistency in proxy records for M2, which will allow these and future M2 sensitivity tests to be interrogated

  19. Complete Suppression of the m=2/n=1 NTM Using ECCD on DIII-D

    International Nuclear Information System (INIS)

    Petty, C.C.; La Haye, R.J.; Luce, T.C.; Humphreys, D.A.; Lohr, J.; Prater, R.; Austin, M.E.; Harvey, R.W.; Wade, M.R.

    2003-01-01

    Complete suppression of the m=2/n=1 neoclassical tearing mode (NTM) is reported for the first time using electron cyclotron current drive (ECCD) to noninductively generate current at the radius of the island O-point. Experiments on the DIII-D tokamak show that the maximum shrinkage of the m=2/n=1 island amplitude occurs when the ECCD location coincides with the q=2 surface. Estimates of the ECCD radial profile width from the island shrinkage are consistent with ray tracing calculations but may allow for a factor-of-1.5 broadening from electron radial transport

  20. Control software architecture and operating modes of the Model M-2 maintenance system

    International Nuclear Information System (INIS)

    Satterlee, P.E. Jr.; Martin, H.L.; Herndon, J.N.

    1984-04-01

    The Model M-2 maintenance system is the first completely digitally controlled servomanipulator. The M-2 system allows dexterous operations to be performed remotely using bilateral force-reflecting master/slave techniques, and its integrated operator interface takes advantage of touch-screen-driven menus to allow selection of all possible operating modes. The control system hardware for this system has been described previously. This paper describes the architecture of the overall control system. The system's various modes of operation are identified, the software implementation of each is described, system diagnostic routines are described, and highlights of the computer-augmented operator interface are discussed. 3 references, 5 figures

  1. All Trans Retinoic Acid, Transforming Growth Factor β and Prostaglandin E2 in Mouse Plasma Synergize with Basophil-Secreted Interleukin-4 to M2 Polarize Murine Macrophages.

    Directory of Open Access Journals (Sweden)

    Victor W Ho

    Full Text Available In previous studies we found that macrophages (MФs from SH2-containing inositol-5'-phosphatase (SHIP deficient mice are M2 polarized while their wild type (WT counterparts are M1 polarized and that this difference in MФ phenotype can be recapitulated during in vitro derivation from bone marrow if mouse plasma (MP, but not fetal calf serum, is added to standard M-CSF-containing cultures. In the current study we investigated the mechanism by which MP skews SHIP-/- but not +/+ MФs to an M2 phenotype. Our results suggest that SHIP-/- basophils constitutively secrete higher levels of IL-4 than SHIP+/+ basophils and this higher level of IL-4 is sufficient to skew both SHIP+/+ and SHIP-/- MФs to an M2 phenotype, but only when MP is present to increase the sensitivity of the MФs to this level of IL-4. MP increases the IL-4 sensitivity of both SHIP+/+ and -/- MФs not by increasing cell surface IL-4 or CD36 receptor levels, but by triggering the activation of Erk and Akt and the production of ROS, all of which play a critical role in sensitizing MФs to IL-4-induced M2 skewing. Studies to identify the factor(s in MP responsible for promoting IL-4-induced M2 skewing suggests that all-trans retinoic acid (ATRA, TGFβ and prostaglandin E2 (PGE2 all play a role. Taken together, these results indicate that basophil-secreted IL-4 plays an essential role in M2 skewing and that ATRA, TGFβ and PGE2 within MP collaborate to dramatically promote M2 skewing by acting directly on MФs to increase their sensitivity to IL-4.

  2. Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

    Science.gov (United States)

    Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

    2013-02-01

    This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

  3. 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.

  4. Effect of ion beam bombardment on the carbide in M2 steel modified by ion-beam-assisted deposition

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.Y.; Wang, F.J.; Wang, Y.K. (Dept. of Materials Engineering, Dalian Univ. of Technology (China)); Ma, T.C. (National Lab. of Materials Modification by Beam Three, Dalian (China))

    1991-10-30

    Transmission electron microscopy was used to study the effect of nitrogen ion bombardment with different doses on the carbides in M2 high speed steel as the nitrogen ions penetrated into the nitride films during ion-beam-assisted deposition. With different doses of nitrogen, alterations in the morphological characteristics of the carbide M6C at the interface were observed. With lower doses, knitting-like contrast within the carbide showed subboundary structure defects in M6C. With increasing dose, the substructure defects were broken up into small fragments owing to heavy bombardment. The microstructures of carbides at the interface damaged by nitrogen ions are discussed in detail. (orig.).

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

    Science.gov (United States)

    1963-01-01

    After initial ground-tow flights of the M2-F1 using the Pontiac as a tow vehicle, the way was clear to make air tows behind a C-47. The first air tow took place on 16 August 1963. Pilot Milt Thompson found that the M2-F1 flew well, with good control. This first flight lasted less than two minutes from tow-line release to touchdown. The descent rate was 4,000 feet per minute. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got

  6. Investigation into adamantane-based M2 inhibitors with FB-QSAR.

    Science.gov (United States)

    Wei, Hang; Wang, Cheng-Hua; Du, Qi-Shi; Meng, Jianzong; Chou, Kuo-Chen

    2009-07-01

    Because of their high resistance rate to the existing drugs, influenza A viruses have become a threat to human beings. It is known that the replication of influenza A viruses needs a pH-gated proton channel, the so-called M2 channel. Therefore, to develop effective drugs against influenza A, the most logic strategy is to inhibit the M2 channel. Recently, the atomic structure of the M2 channel was determined by NMR spectroscopy (Schnell, J.R. and Chou, J.J., Nature, 2008, 451, 591-595). The high-resolution NMR structure has provided a solid basis for structure-based drug design approaches. In this study, a benchmark dataset has been constructed that contains 34 newly-developed adamantane-based M2 inhibitors and covers considerable structural diversities and wide range of bioactivities. Based on these compounds, an in-depth analysis was performed with the newly developed fragment-based quantitative structure-activity relationship (FB-QSAR) algorithm. The results thus obtained provide useful insights for dealing with the drug-resistant problem and designing effective adamantane-based antiflu drugs.

  7. Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion.

    Science.gov (United States)

    Chen, Yu; Deng, Xiaoling; Deng, Junfang; Zhou, Jiehua; Ren, Yuping; Liu, Shengxuan; Prusak, Deborah J; Wood, Thomas G; Bao, Xiaoyong

    2016-12-01

    Human metapneumovirus (hMPV) is a major cause of lower respiratory infection in young children. Repeated infections occur throughout life, but its immune evasion mechanisms are largely unknown. We recently found that hMPV M2-2 protein elicits immune evasion by targeting mitochondrial antiviral-signaling protein (MAVS), an antiviral signaling molecule. However, the molecular mechanisms underlying such inhibition are not known. Our mutagenesis studies revealed that PDZ-binding motifs, 29-DEMI-32 and 39-KEALSDGI-46, located in an immune inhibitory region of M2-2, are responsible for M2-2-mediated immune evasion. We also found both motifs prevent TRAF5 and TRAF6, the MAVS downstream adaptors, to be recruited to MAVS, while the motif 39-KEALSDGI-46 also blocks TRAF3 migrating to MAVS. In parallel, these TRAFs are important in activating transcription factors NF-kB and/or IRF-3 by hMPV. Our findings collectively demonstrate that M2-2 uses its PDZ motifs to launch the hMPV immune evasion through blocking the interaction of MAVS and its downstream TRAFs. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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 arriva...

  9. Initial search for triggered gamma emission from Hf-178(m2) using the YSU miniball array

    Czech Academy of Sciences Publication Activity Database

    Carroll, J. J.; Burnett, J.; Drummond, T.; Lepak, J.; Propri, R.; Smith, D.; Karamian, S. A.; Adam, Jindřich; Stedile, F.; Agee, FJ.

    2002-01-01

    Roč. 143, 1, 2, 3, 4 (2002), s. 37-54 ISSN 0304-3843 Institutional research plan: CEZ:AV0Z1048901 Keywords : triggered gamma emission * Hf-178(m2) * nuclear batteries Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 0.533, year: 2002

  10. Almost optimal distributed M2M multicasting in wireless mesh networks

    DEFF Research Database (Denmark)

    Xin, Qin; Manne, Fredrik; Zhang, Yan

    2012-01-01

    Wireless Mesh Networking (WMN) is an emerging communication paradigm to enable resilient, cost-efficient and reliable services for the future-generation wireless networks. In this paper, we study the problem of multipoint-to- multipoint (M2M) multicasting in a WMN which aims to use the minimum nu...

  11. Formation of the high-spin Hf-179m2 isomer in reactor irradiations

    Czech Academy of Sciences Publication Activity Database

    Karamian, S. A.; Carroll, J. J.; Adam, Jindřich; Kulagin, EN.; Shabalin, EP.

    2004-01-01

    Roč. 14, č. 4 (2004), s. 438-441 ISSN 1054-660X R&D Projects: GA MŠk(CZ) ME 134 Keywords : reactor irradiation * high-spin Hf-179m2 Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 0.836, year: 2004

  12. 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...

  13. M2-F1 mounted in NASA Ames Research Center 40x80 foot wind tunnel

    Science.gov (United States)

    1962-01-01

    After the first attempted ground-tow tests of the M2-F1 in March 1963, the vehicle was taken to the Ames Research Center, Mountain View, CA, for wind-tunnel testing. During these tests, Milt Thompson and others were in the M2-F1 to position the control surfaces for each test. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C

  14. A Survey on M2M Systems for mHealth: A Wireless Communications Perspective

    Directory of Open Access Journals (Sweden)

    Elli Kartsakli

    2014-09-01

    Full Text Available In the new era of connectivity, marked by the explosive number of wireless electronic devices and the need for smart and pervasive applications, Machine-to-Machine (M2M communications are an emerging technology that enables the seamless device interconnection without the need of human interaction. The use of M2M technology can bring to life a wide range of mHealth applications, with considerable benefits for both patients and healthcare providers. Many technological challenges have to be met, however, to ensure the widespread adoption of mHealth solutions in the future. In this context, we aim to provide a comprehensive survey on M2M systems for mHealth applications from a wireless communication perspective. An end-to-end holistic approach is adopted, focusing on different communication aspects of the M2M architecture. Hence, we first provide a systematic review ofWireless Body Area Networks (WBANs, which constitute the enabling technology at the patient’s side, and then discuss end-to-end solutions that involve the design and implementation of practical mHealth applications. We close the survey by identifying challenges and open research issues, thus paving the way for future research opportunities.

  15. Growth and properties of M2-xCexCuO4+d single crystals

    International Nuclear Information System (INIS)

    Matacotta, F.C.; Morales de La Garza, L.; Nevriva, M.; Nardin, G.; Randaccio, L.; Zangrando, E.

    1989-10-01

    The M 2-x Ce x CuO 4+d crystals where M is a rare earth ion (like Nd, Pr etc.) were prepared by a modified flux method, their structure has been investigated by scanning electron microscopy and energy dispersive X-ray analysis and the electrical resistivity was measured on a number of crystals. 5 refs, 3 figs, 3 tabs

  16. Efficient LTE Access with Collision Resolution for Massive M2M Communications

    DEFF Research Database (Denmark)

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

    2014-01-01

    outage. In this work we propose a LTE RACH scheme tailored for delay-sensitive M2M services with synchronous traffic arrivals. The key idea is, upon detection of a RACH overload, to apply a collision resolution algorithm based on splitting trees. The solution is implemented on top of the existing LTE...

  17. Macrophages during the fibrotic process: M2 as friend and foe.

    Directory of Open Access Journals (Sweden)

    Tarcio Teodoro Braga

    2015-11-01

    Full Text Available Macrophages play essential activities in homeostasis maintenance, tissue regeneration and wound healing. However, when the physiological process of wound healing is deregulated by persistent insults and chronic diseases, macrophages can participate actively in the development of fibrosis. In this regard, the exacerbation or resolution of fibrosis depends on the type of macrophages polarized and the severity and duration of the inflammatory insult. M1 macrophages use glycolytic metabolism to optimize oxygen consumption and activate myofibroblasts and fibrocytes. On the other hand, M2 macrophages, which use oxidative metabolism, have anti-inflammatory properties due to their capacity to produce and secrete IL-10, TGFβ and arginase that promotes tissue repair. However, when the primary insult is not controlled and there is a persistent M2 macrophage activity, these cells promote ECM deposition through the continuous production of TGFβ and growth factors. In this scenario, M2 macrophages act as a break point between normal wound healing and the pro-fibrotic process. Here, we review the aspects of tissue repair based on macrophage biology and we evidence scar formation is directly related to the degree of inflammation, but also with the appearance of M2 macrophages.

  18. Multiple promoters drive tissue-specific expression of the human M2 muscarinic acetylcholine receptor gene

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Alena; Bruce, A. W.; Doležal, Vladimír; Tuček, Stanislav; Buckley, N. J.

    2004-01-01

    Roč. 91, č. 1 (2004), s. 88-98 ISSN 0022-3042 R&D Projects: GA AV ČR IAA5011306 Institutional research plan: CEZ:AV0Z5011922 Keywords : M2 muscarinic receptor * neuron-restrictive silence factor * promoter Subject RIV: ED - Physiology Impact factor: 4.824, year: 2004

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

    KAUST Repository

    Gandi, Appala; Alshareef, Husam N.; Schwingenschlö gl, Udo

    2016-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    María Carolina Ortiz

    Full Text Available Current data suggest that Neisseria gonorrhoeae is able to suppress the protective immune response at different levels, such as B and T lymphocytes and antigen-presenting cells. The present report is focused on gonococcus evasion mechanism on macrophages (MФ and its impact in the subsequent immune response. In response to various signals MФ may undergo classical-M1 (M1-MФ or alternative-M2 (M2-MФ activation. Until now there are no reports of the gonococcus effects on human MФ polarization. We assessed the phagocytic ability of monocyte-derived MФ (MDM upon gonococcal infection by immunofluorescence and gentamicin protection experiments. Then, we evaluated cytokine profile and M1/M2 specific-surface markers on MФ challenged with N. gonorrhoeae and their proliferative effect on T cells. Our findings lead us to suggest N. gonorrhoeae stimulates a M2-MФ phenotype in which some of the M2b and none of the M1-MФ-associated markers are induced. Interestingly, N. gonorrhoeae exposure leads to upregulation of a Programmed Death Ligand 1 (PD-L1, widely known as an immunosuppressive molecule. Moreover, functional results showed that N. gonorrhoeae-treated MФ are unable to induce proliferation of human T-cells, suggesting a more likely regulatory phenotype. Taken together, our data show that N. gonorroheae interferes with MФ polarization. This study has important implications for understanding the mechanisms of clearance versus long-term persistence of N. gonorroheae infection and might be applicable for the development of new therapeutic strategies.

  1. Construction of Δm2--sin2 2θ plots

    International Nuclear Information System (INIS)

    Snyder, R.

    1991-01-01

    In the two-flavor approximation, the probability for a neutrino to oscillate from one flavor to the other is given by Ρ νa → νb = sin 2 2θ sin 2 (1.27 Δm 2 L/E ν ) where θ is the mixing angle, Δm 2 = |m νa 2 - m νb 2 | is measured in (eV/c 2 ) 2 , L, the distance from the source, is measured in km, and E, the beam energy, is measured in GeV. If either Δm 2 or sin 2 2Θ is zero, there is no oscillation. They might also have small, non-zero values, causing the oscillations to be so small as to be unobservable in a particular experiment. They may also have values which allow us to determine the probability of oscillation, but so far no compelling evidence for oscillation exists. The universal method of portraying what region of parameter space is explored by a neutrino oscillation experiment is to mark off an area on a Δm 2 vs. sin 2 2θ plot. Typically, a line is graphed, with the claim that if the experiment finds not evidence of oscillation, one can, for example, be 90% certain that Δm 2 and sin 2 2θ lie within the region below and to the left of the line. Since these plots are so widely used, it is useful to understand the process by which they are created

  2. 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

  3. 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.

  4. Endovascular thrombectomy for M2 occlusions: comparison between forced arterial suction thrombectomy and stent retriever thrombectomy.

    Science.gov (United States)

    Kim, Yong-Won; Son, Seungnam; Kang, Dong-Hun; Hwang, Yang-Ha; Kim, Yong-Sun

    2017-07-01

    To date there has been no direct comparison of two frequently used endovascular thrombectomy (EVT) methods (forced arterial suction thrombectomy (FAST) and stent retriever thrombectomy) in M2 occlusions. We review our experiences with EVT performed using FAST and stent retriever thrombectomy in such cases. The subjects comprised 41 patients with an M2 occlusion who underwent EVT (25 with FAST, 16 with stent retriever thrombectomy). The patients' data were retrospectively analyzed to evaluate the technical characteristics and angiographic outcome of the two EVT techniques. Thrombolysis In Cerebral Infarction (TICI) grades 2b-3 using the first chosen technique did not differ significantly between the two techniques (FAST 64.0% vs stent retriever thrombectomy 81.2%, p=0.305). Time from groin puncture to reperfusion was significantly shorter for stent retriever thrombectomy (53.0 vs 38.5 min; p=0.045). Distal embolization occurred in three cases (12.0%) in the FAST group and in four (26.7%) in the stent retriever group (p=0.362). However, the two techniques did not differ significantly in the final TICI 2b-3 rate (72.0% vs 87.5%; p=0.441). A frequent angiographic finding regarding the failure of FAST was that the M2 occlusion was located immediately after severe acute angulation between M1 and M2. Stent retriever thrombectomy may provide faster reperfusion than FAST, while the FAST technique might be associated with lower distal embolization and a higher reperfusion rate for the first thrombectomy attempt, but without any significant difference in clinical outcome. When choosing the EVT method for M2 occlusions, consideration of the location of the occlusion and tortuosity between M1 and M2 might be helpful to achieve a better angiographic outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. High-dose dexamethasone or all-trans-retinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia.

    Science.gov (United States)

    Feng, Q; Xu, M; Yu, Y Y; Hou, Y; Mi, X; Sun, Y X; Ma, S; Zuo, X Y; Shao, L L; Hou, M; Zhang, X H; Peng, J

    2017-09-01

    Essentials M1/M2 imbalance is involved in many autoimmune diseases, and could be restored. The expressions and functions of M1 and M2 were investigated in an in vitro culture system. A preferred M1 polarization is involved in the pathogenesis of immune thrombocytopenia (ITP). High-dose dexamethasone or all-trans-retinoic acid restores M1/M2 balance in ITP patients. Background Immune thrombocytopenia (ITP) is an autoimmune disorder. Deficiency of immune tolerance in antigen-presenting cells and cross-communication between antigen-presenting cells and T cells are involved in the pathogenesis of ITP. Macrophages can polarize into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to different environmental stimuli, and have diverse immunologic functions. Objectives To investigate the M1/M2 imbalance in ITP and whether high-dose dexamethasone (HD-DXM) or all-trans-retinoic acid (ATRA) could restore this imbalance. Methods The numbers of M1 and M2 macrophages in the spleens of ITP patients and patients with traumatic spleen rupture were analyzed by immunofluorescence. Monocyte-derived macrophages were cultured and induced with cytokines and drugs. The expression of M1 and M2 markers and functions of M1 and M2 macrophages before and after modulation by HD-DXM or ATRA were evaluated with flow cytometry and ELISA. Results There was preferred M1 polarization in ITP spleens as compared with healthy controls. Monocyte-derived macrophages from ITP patients had increased expression of M1 markers and impaired immunosuppressive functions. Either HD-DXM or ATRA corrected this imbalance by decreasing the expression of M1 markers and increasing the expression of M2 markers. Moreover, HD-DXM-modulated or ATRA-modulated macrophages suppressed both CD4 + and CD8 + T-cell proliferation and expanded CD4 + CD49 + LAG3 + type 1 T-regulatory cells. HD-DXM or ATRA modulated macrophages to shift the T-cell cytokine profile towards Th2. Treating patients with HD-DXM or ATRA

  6. 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.

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

    International Nuclear Information System (INIS)

    Kai, Chen; Ming-Qi, Cui; Fen, Yan; Li-Juan, Sun; Lei, Zheng; Chen-Yan, Ma; Shi-Bo, Xi; Yi-Dong, Zhao; Jia, Zhao

    2008-01-01

    We present magneto-optical (MO) Faraday spectra measured around the M 2,3 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 M 2,3 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

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

    International Nuclear Information System (INIS)

    Gomis, Jaume; Floch, Bruno Le

    2016-01-01

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

  9. Wilson loops on three-manifolds and their M2-brane duals

    International Nuclear Information System (INIS)

    Farquet, Daniel; Sparks, James

    2014-01-01

    We compute the large N limit of Wilson loop expectation values for a broad class of N=2 supersymmetric gauge theories defined on a general class of background three-manifolds M_3, diffeomorphic to S"3. We find a simple closed formula which depends on the background geometry only through a certain supersymmetric Killing vector field. The supergravity dual of such a Wilson loop is an M2-brane wrapping the M-theory circle, together with a complex curve Σ_2 in a self-dual Einstein manifold M_4, whose conformal boundary is M_3. We show that the regularized action of this M2-brane also depends only on the supersymmetric Killing vector, precisely reproducing the large N field theory computation.

  10. 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

    to that a comprehensive framework has been developed, with the aim of ensuring systematic management, implementation and continuous improvement of the ecodesign process. The framework, called Ecodesign Maturity Model (EcoM2), enables the diagnosis of the company’s ecodesign maturity profile; the identification...... 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......Despite the recognition of the potential benefits of ecodesign, a promising approach to integrate environmental concerns into the product development process, its application has failed to reach large numbers of companies and sectors worldwide due to managerial difficulties. In response...

  11. Access Control in IoT/M2M - Cloud Platform

    DEFF Research Database (Denmark)

    Anggorojati, Bayu

    Billions of devices are connected to the Internet nowadays, and the number will continue to grow in the future thanks to the advances in the electronics and telecommunication technology developments. Its application in broad aspects of human’s life brings a lot of benefits by improving productivity...... 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 Io......T have shown that the concern about the security and privacy play a huge role for the mass adoption of the IoT/M2M as cloud services. Among the important topics within the security and privacy, the access control is an important mechanism, which essentially manages how the important assets or resource...

  12. The new VLT-DSM M2 unit: construction and electromechanical testing

    Science.gov (United States)

    Gallieni, Daniele; Biasi, Roberto

    2013-12-01

    We present the design, construction and validation of the new M2 unit of the VLT Deformable Secondary Mirror. In the framework of the Adaptive Optics Facility program, ADS and Microgate designed a new secondary unit which replaces the current Dornier one. The M2 is composed by the mechanical structure, a new hexapod positioner and the Deformable Secondary Mirror unit.The DSM is based on the well proven contactless, voice coil motor technology that has been already successfully implemented in the MMT, LBT and Magellan adaptive secondaries, and is considered a promising technical choice for the E-ELT M4 and the GMT ASM. The VLT adaptive unit has been fully integrated and, before starting the optical calibration, has completed the electromechanical characterization, focused on the dynamic performance. With respect to the previous units we introduced several improvements, both in hardware and control architecture that allowed achieving a significant enhancement of the system dynamics and reduction of power consumption.

  13. A novel allele of TaGW2-A1 is located in a finely mapped QTL that increases grain weight but decreases grain number in wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhai, Huijie; Feng, Zhiyu; Du, Xiaofen; Song, Yane; Liu, Xinye; Qi, Zhongqi; Song, Long; Li, Jiang; Li, Linghong; Peng, Huiru; Hu, Zhaorong; Yao, Yingyin; Xin, Mingming; Xiao, Shihe; Sun, Qixin; Ni, Zhongfu

    2018-03-01

    A novel TaGW2-A1 allele was identified from a stable, robust QTL region, which is pleiotropic for thousand grain weight, grain number per spike, and grain morphometric parameters in wheat. Thousand grain weight (TGW) and grain number per spike (GNS) are two crucial determinants of wheat spike yield, and genetic dissection of their relationships can help to fine-tune these two components and maximize grain yield. By evaluating 191 recombinant inbred lines in 11 field trials, we identified five genomic regions on chromosomes 1B, 3A, 3B, 5B, or 7A that solely influenced either TGW or GNS, and a further region on chromosome 6A that concurrently affected TGW and GNS. The QTL of interest on chromosome 6A, which was flanked by wsnp_BE490604A_Ta_2_1 and wsnp_RFL_Contig1340_448996 and designated as QTgw/Gns.cau-6A, was finely mapped to a genetic interval shorter than 0.538 cM using near isogenic lines (NILs). The elite NILs of QTgw/Gns.cau-6A increased TGW by 8.33%, but decreased GNS by 3.05% in six field trials. Grain Weight 2 (TaGW2-A1), a well-characterized gene that negatively regulates TGW and grain width in wheat, was located within the finely mapped interval of QTgw/Gns.cau-6A. A novel and rare TaGW2-A1 allele with a 114-bp deletion in the 5' flanking region was identified in the parent with higher TGW, and it reduced TaGW2-A1 promoter activity and expression. In conclusion, these results expand our knowledge of the genetic and molecular basis of TGW-GNS trade-offs in wheat. The QTLs and the novel TaGW2-A1 allele are likely useful for the development of cultivars with higher TGW and/or higher GNS.

  14. 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

  15. Giant graviton interactions and M2-branes ending on multiple M5-branes

    Science.gov (United States)

    Hirano, Shinji; Sato, Yuki

    2018-05-01

    We study splitting and joining interactions of giant gravitons with angular momenta N 1/2 ≪ J ≪ N in the type IIB string theory on AdS 5 × S 5 by describing them as instantons in the tiny graviton matrix model introduced by Sheikh-Jabbari. At large J the instanton equation can be mapped to the four-dimensional Laplace equation and the Coulomb potential for m point charges in an n-sheeted Riemann space corresponds to the m-to- n interaction process of giant gravitons. These instantons provide the holographic dual of correlators of all semi-heavy operators and the instanton amplitudes exactly agree with the pp-wave limit of Schur polynomial correlators in N = 4 SYM computed by Corley, Jevicki and Ramgoolam. By making a slight change of variables the same instanton equation is mathematically transformed into the Basu-Harvey equation which describes the system of M2-branes ending on M5-branes. As it turns out, the solutions to the sourceless Laplace equation on an n-sheeted Riemann space correspond to n M5-branes connected by M2-branes and we find general solutions representing M2-branes ending on multiple M5-branes. Among other solutions, the n = 3 case describes an M2-branes junction ending on three M5-branes. The effective theory on the moduli space of our solutions might shed light on the low energy effective theory of multiple M5-branes.

  16. Genetic variability for different quantitative traits in M2 generations of opium poppy (Papaver somniferum L.)

    International Nuclear Information System (INIS)

    Chatterjee, A.; Shukla, S.; Singh, S.P.

    2004-01-01

    An experiment on induced mutation in two varieties of opium poppy was laid out to create new genetic variability for isolation of high yielding genotypes. Varieties NBRI-1 and NBRI-5 were subjected to irradiation for five doses of gamma rays and NBRI-5 was also treated with four doses of EMS and 20 mixed doses of EMS plus gamma rays. The data were recorded on 15 plants/treatment for 10 polygenic characters as pooled in M1 and M2 generations separately as well as in each dose-wise in M2 population. The results indicated that GCV, heritability and genetic advance were higher in M1 than M2 in both the varieties for all the traits except for opium and seed yield. The genetic advance was consistently high for opium yield, seed yield and capsule weight in all the doses for both the varieties with some exception. The dose level of kR10 and kR30 in NBRI-1 revealed high GCV, heritability and genetic advance for seed weight. These treatment levels also had high values of all these three genetic parameters for capsules per plant, capsule size and capsule weight. The values of these three parameters were also high for all the doses in M2 generations of both the varieties for opium yield, seed weight, capsule weight and capsule size in comparison to control. The GCV, heritability and genetic advance were consistently high for all the mixed doses in NBRI-5 for opium yield, seed weight and capsule weight, with some exception [it

  17. Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

    OpenAIRE

    Selleri, Silvia; Bifsha, Panojot; Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Ren?e; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle

    2016-01-01

    Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-...

  18. 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.

  19. Carbides crystalline structure of AISI M2 high-speed steel

    International Nuclear Information System (INIS)

    Serna, M.M.; Galego, E.; Rossi, J.L.

    2005-01-01

    The aim of this study was to identify the crystallographic structure of the extracted carbides of AISI M2 steel spray formed The structure determination of these carbides. The structure determination of these carbides is a very hard work. Since these structures were formed by atom migration it is not possible to reproduce them by a controlled process with a determined chemical composition. The solution of this problem is to obtain the carbide by chemical extraction from the steel. (Author)

  20. 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.

  1. Protective role of NKT cells and macrophage M2-driven phenotype in bleomycin-induced pulmonary fibrosis.

    Science.gov (United States)

    Grabarz, Felipe; Aguiar, Cristhiane Favero; Correa-Costa, Matheus; Braga, Tárcio Teodoro; Hyane, Meire I; Andrade-Oliveira, Vinícius; Landgraf, Maristella Almeida; Câmara, Niels Olsen Saraiva

    2018-04-01

    Pulmonary fibrosis is a result of an abnormal wound healing in lung tissue triggered by an excessive accumulation of extracellular matrix proteins, loss of tissue elasticity, and debit of ventilatory function. NKT cells are a major source of Th1 and Th2 cytokines and may be crucial in the polarization of M1/M2 macrophages in pulmonary fibrogenesis. Although there appears to be constant scientific progress in that field, pulmonary fibrosis still exhibits no current cure. From these facts, we hypothesized that NKT cells could influence the development of pulmonary fibrosis via modulation of macrophage activation. Wild type (WT) and NKT type I cell-deficient mice (Jα18 -/- ) were subjected to the protocol of bleomycin-induced pulmonary fibrosis with or without treatment with NKT cell agonists α-galactosylceramide and sulfatide. The participation of different cell populations, collagen deposition, and protein levels of different cytokines involved in inflammation and fibrosis was evaluated. The results indicate a benign role of NKT cells in Jα18 -/- mice and in wild-type α-galactosylceramide-sulfatide-treated groups. These animals presented lower levels of collagen deposition, fibrogenic molecules such as TGF-β and vimentin and improved survival rates. In contrast, WT mice developed a Th2-driven response augmenting IL-4, 5, and 13 protein synthesis and increased collagen deposition. Furthermore, the arginase-1 metabolic pathway was downregulated in wild-type NKT-activated and knockout mice indicating lower activity of M2 macrophages in lung tissue. Hence, our data suggest that NKT cells play a protective role in this experimental model by down modulating the Th2 milieu, inhibiting M2 polarization and finally preventing fibrosis.

  2. Resolving combinatorial ambiguities in dilepton t t¯ event topologies with constrained M2 variables

    Science.gov (United States)

    Debnath, Dipsikha; Kim, Doojin; Kim, Jeong Han; Kong, Kyoungchul; Matchev, Konstantin T.

    2017-10-01

    We advocate the use of on-shell constrained M2 variables in order to mitigate the combinatorial problem in supersymmetry-like events with two invisible particles at the LHC. We show that in comparison to other approaches in the literature, the constrained M2 variables provide superior ansätze for the unmeasured invisible momenta and therefore can be usefully applied to discriminate combinatorial ambiguities. We illustrate our procedure with the example of dilepton t t ¯ events. We critically review the existing methods based on the Cambridge MT 2 variable and MAOS reconstruction of invisible momenta, and show that their algorithm can be simplified without loss of sensitivity, due to a perfect correlation between events with complex solutions for the invisible momenta and events exhibiting a kinematic endpoint violation. Then we demonstrate that the efficiency for selecting the correct partition is further improved by utilizing the M2 variables instead. Finally, we also consider the general case when the underlying mass spectrum is unknown, and no kinematic endpoint information is available.

  3. 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.

  4. 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.

  5. 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.

  6. M2-9 - a planetary nebula with an eruptive nucleus?

    International Nuclear Information System (INIS)

    Balick, B.

    1989-01-01

    M2-9 is a striking bipolar, or butterfly, planetary nebula (PN) whose nuclear spectrum is uncharacteristic of PN nuclei. Narrow lines ranging in ionization from O I, Fe II, forbidden Fe II, and Si II through forbidden O III are observed in the stellar spectrum. The H-alpha emission line has wings extending nearly 11,000 km/s at the base, and there is a deep self-absorption feature near the H-alpha line peak at the same velocity as nebular gas observed in one of the two bipolar lobes. The spectrum of M2-9's nucleus is more similar to the slow nova RR Tel, some symbiotic stars, and Seyfert (type 1.9) galactic nuclei than the central stars of most other PNs. Although its morphology, size, and nebular spectrum share many similarities with other PNs, M2-9 may not share a common evolutionary history with that class of objects. 31 references

  7. Toward a proof of Montonen-Olive duality via multiple M2-branes

    International Nuclear Information System (INIS)

    Hashimoto, Koji; Tai, Ta-Sheng; Terashima, Seiji

    2009-01-01

    We derive 4-dimensional N = 4 U(N) supersymmetric Yang-Mills theory from a 3-dimensional Chern-Simons-matter theory with product gauge group (U(N)) 2n . The latter describes M2-branes probing an orbifold where a torus emerges in a scaling limit. It is expected that the SL(2,Z) duality of the 4-dimensional Yang-Mills theory will be shown in M-theory point of view since it is trivially realized as modular transformations of the torus. Indeed, starting from one single Chern-Simons-matter theory, we find infinitely many equivalent 4-dimensional theories differing up to T-transformation of the SL(2,Z) redefinition of the gauge coupling τ = θ/2π + 4πi/g 2 and a parity transformation in 4 dimensions. Although S-transformation can not be shown in our work, it is important that a part of the SL(2,Z) transformation is realized via the M2-brane action. Thus we think our work can be a step toward a proof of Montonen-Olive duality via M2-branes.

  8. Toward a proof of Montonen-Olive duality via multiple M2-branes

    Science.gov (United States)

    Hashimoto, Koji; Tai, Ta-Sheng; Terashima, Seiji

    2009-04-01

    We derive 4-dimensional Script N = 4 U(N) supersymmetric Yang-Mills theory from a 3-dimensional Chern-Simons-matter theory with product gauge group (U(N))2n. The latter describes M2-branes probing an orbifold where a torus emerges in a scaling limit. It is expected that the SL(2,Z) duality of the 4-dimensional Yang-Mills theory will be shown in M-theory point of view since it is trivially realized as modular transformations of the torus. Indeed, starting from one single Chern-Simons-matter theory, we find infinitely many equivalent 4-dimensional theories differing up to T-transformation of the SL(2,Z) redefinition of the gauge coupling τ = θ/2π + 4πi/g2 and a parity transformation in 4 dimensions. Although S-transformation can not be shown in our work, it is important that a part of the SL(2,Z) transformation is realized via the M2-brane action. Thus we think our work can be a step toward a proof of Montonen-Olive duality via M2-branes.

  9. 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

  10. Non-Neuronal Functions of the M2 Muscarinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Ritva Tikkanen

    2013-04-01

    Full Text Available Acetylcholine is an important neurotransmitter whose effects are mediated by two classes of receptors. The nicotinic acetylcholine receptors are ion channels, whereas the muscarinic receptors belong to the large family of G protein coupled seven transmembrane helix receptors. Beyond its function in neuronal systems, it has become evident that acetylcholine also plays an important role in non-neuronal cells such as epithelial and immune cells. Furthermore, many cell types in the periphery are capable of synthesizing acetylcholine and express at least some of the receptors. In this review, we summarize the non-neuronal functions of the muscarinic acetylcholine receptors, especially those of the M2 muscarinic receptor in epithelial cells. We will review the mechanisms of signaling by the M2 receptor but also the cellular trafficking and ARF6 mediated endocytosis of this receptor, which play an important role in the regulation of signaling events. In addition, we provide an overview of the M2 receptor in human pathological conditions such as autoimmune diseases and cancer.

  11. 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.

  12. M2 macrophages coexist with a Th1-driven profile in periapical cysts.

    Science.gov (United States)

    Ribeiro, C M; de Carli, M L; Nonogaki, S; Nogueira, D A; Pereira, A A C; Sperandio, F F; Hanemann, J A C

    2018-02-01

    To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines. Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  13. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

    Science.gov (United States)

    Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

    2016-04-01

    Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

  14. The state-of-the-art Model M-2 Maintenance System

    International Nuclear Information System (INIS)

    Herndon, J.N.; Martin, H.L.; Satterlee, P.E. Jr.; Jelatis, D.G.; Jennrich, C.E.

    1984-01-01

    The Model M-2 Maintenance System is part of an ongoing program within the Consolidated Fuel Reprocessing Program (CFRP) at Oak Ridge National Laboratory (ORNL) to improve remote manipulation technology for future nuclear fuel reprocessing and other remote applications. Techniques, equipment, and guidelines which can improve the efficiency of remote maintenance are being developed. The Model M-2 Maintenance System, installed in the Integrated Equipment Test (IET) Facility at ORNL, provides a complete, integrated remote maintenance system for the demonstration and development of remote maintenance techniques. The system comprises a pair of force-reflecting servomanipulator arms, television viewing, lighting, and auxiliary lifting capabilities, thereby allowing manlike maintenance operations to be executed remotely within the remote cell mockup area in the IET. The Model M-2 Maintenance System incorporates an upgraded version of the proven Central Research Laboratories' Model M servomanipulator. Included are state-of-the-art brushless dc servomotors for improved performance, remotely removable wrist assemblies, geared azimuth drive, and a distributed microprocessor-based digital control system

  15. 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

  16. SULFUR- AND SILICON-BEARING MOLECULES IN PLANETARY NEBULAE: THE CASE OF M2-48

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, J. L.; Ziurys, L. M., E-mail: lziurys@email.arizona.edu [Department of Chemistry, The University of Arizona, P.O. Box 210041, Tucson, AZ 85721 (United States)

    2014-10-20

    Molecular-line observations of the bipolar planetary nebula (PN) M2-48 have been conducted using the Sub-Millimeter Telescope and the 12 m antenna of the Arizona Radio Observatory at 1, 2, and 3 mm. M2-48 is estimated to be ∼4800 yr old, midway through the PN evolutionary track. SiO and SO{sub 2} were detected in this source—the first identification of either molecule in a PN. CN, HCN, HNC, CS, SO, HCO{sup +}, N{sub 2}H{sup +}, and several {sup 13}C isotopologues such as {sup 13}CN, H{sup 13}CN, and H{sup 13}CO{sup +} were also observed toward this object. A radiative transfer analysis of multiple SiO transitions indicates a gas kinetic temperature of T {sub K} ∼ 55 K and a density of n(H{sub 2}) ∼ 9 × 10{sup 5} cm{sup –3} in M2-48, in agreement with previous CS and CO modeling. After CO, CN, and SO were found to be the most prevalent molecules in this nebula, with fractional abundances, relative to H{sub 2}, of f ∼ 3.8 × 10{sup –7} and 2.4 × 10{sup –7}, respectively. SO{sub 2} and HCN are also abundant, with f ∼ 1.2 × 10{sup –7}, indicating an [SO]/[SO{sub 2}] ratio of ∼2. Relatively high ion abundances were measured in M2-48 as well, with f ∼ 10{sup –7} for both HCO{sup +} and N{sub 2}H{sup +}. An [HCN]/[HNC] ratio of ∼2 was determined, as typically observed in other PNe, independent of age. The high abundances of SO and SO{sub 2}, along with the presence of SiO with f ∼ 2.9 × 10{sup –8}, suggest O/C > 1 in this source; furthermore, the prevalence of CN and N{sub 2}H{sup +} indicates nitrogen enrichment. The {sup 12}C/{sup 13}C ratio of ∼3 in the nebula was also established. These factors indicate hot-bottom burning occurred in the progenitor star of M2-48, suggesting an initial mass > 4 M {sub ☉}.

  17. Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel

    Energy Technology Data Exchange (ETDEWEB)

    Pielak, Rafal M. [Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 (United States); Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115 (United States); Chou, James J., E-mail: chou@cmcd.hms.harvard.edu [Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115 (United States)

    2010-10-08

    Research highlights: {yields} This paper reports the structure of the V27A drug resistant mutant of the M2 channel of influenza A virus. {yields} High quality NMR data allowed a better-defined structure for the C-terminal region of the M2 channel. {yields} Using the structure, we propose a proton transfer pathway during M2 proton conduction. {yields} Structural comparison between the wildtype, V27A and S31N variants allowed an in-depth analysis of possible modes of drug resistance. {yields} Distinct feature of the V27A channel pore also provides an explanation for its faster rate of proton conduction. -- Abstract: The M2 protein of influenza A virus forms a proton-selective channel that is required for viral replication. It is the target of the anti-influenza drugs, amantadine and rimantadine. Widespread drug resistant mutants, however, has greatly compromised the effectiveness of these drugs. Here, we report the solution NMR structure of the highly pathogenic, drug resistant mutant V27A. The structure reveals subtle structural differences from wildtype that maybe linked to drug resistance. The V27A mutation significantly decreases hydrophobic packing between the N-terminal ends of the transmembrane helices, which explains the looser, more dynamic tetrameric assembly. The weakened channel assembly can resist drug binding either by destabilizing the rimantadine-binding pocket at Asp44, in the case of the allosteric inhibition model, or by reducing hydrophobic contacts with amantadine in the pore, in the case of the pore-blocking model. Moreover, the V27A structure shows a substantially increased channel opening at the N-terminal end, which may explain the faster proton conduction observed for this mutant. Furthermore, due to the high quality NMR data recorded for the V27A mutant, we were able to determine the structured region connecting the channel domain to the C-terminal amphipathic helices that was not determined in the wildtype structure. The new structural

  18. Mechanical thrombectomy for acute ischemic stroke with occlusion of the M2 segment of the middle cerebral artery: a meta-analysis.

    Science.gov (United States)

    Saber, Hamidreza; Narayanan, Sandra; Palla, Mohan; Saver, Jeffrey L; Nogueira, Raul G; Yoo, Albert J; Sheth, Sunil A

    2017-11-10

    Endovascular thrombectomy has demonstrated benefit for patients with acute ischemic stroke from proximal large vessel occlusion. However, limited evidence is available from recent randomized trials on the role of thrombectomy for M2 segment occlusions of the middle cerebral artery (MCA). We conducted a systematic review and meta-analysis to investigate clinical and radiographic outcomes, rates of hemorrhagic complications, and mortality after M2 occlusion thrombectomy using modern devices, and compared these outcomes against patients with M1 occlusions. Recanalization was defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 or modified TICI 2b/3. A total of 12 studies with 1080 patients with M2 thrombectomy were included in our analysis. Functional independence (modified Rankin Scale 0-2) rate was 59% (95% CI 54% to 64%). Mortality and symptomatic intracranial hemorrhage rates were 16% (95% CI 11% to 23%) and 10% (95% CI 6% to 16%), respectively. Recanalization rates were 81% (95% CI 79% to 84%), and were equally comparable for stent-retriever versus aspiration (OR 1.05; 95% CI 0.91 to 1.21). Successful M2 recanalization was associated with greater rates of favorable outcome (OR 4.22; 95% CI 1.96 to 9.1) compared with poor M2 recanalization (TICI 0-2a). There was no significant difference in recanalization rates for M2 versus M1 thrombectomy (OR 1.05; 95% CI 0.77 to 1.42). This meta-analysis suggests that mechanical thrombectomy for M2 occlusions that can be safely accessed is associated with high functional independence and recanalization rates, but may be associated with an increased risk of hemorrhage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. LASIK flap characteristics using the Moria M2 microkeratome with the 90-microm single use head.

    Science.gov (United States)

    Aslanides, Ioannis M; Tsiklis, Nikolaos S; Astyrakakis, Nikolaos I; Pallikaris, Ioannis G; Jankov, Mirko R

    2007-01-01

    To evaluate the accuracy and consistency of corneal flap thickness, horizontal diameter, and hinge size with the Moria M2 90-microm single use head. Fifty-two myopic patients (104 eyes), mean age 32.6 years, underwent bilateral LASIK with a superior hinged flap using the Moria M2 microkeratome (90-microm single use head). Prospective evaluation included flap thickness (subtraction method), diameter, hinge size, interface particles, intraoperative complications, and visual recovery. The mean preoperative spherical equivalent refraction was -5.72 +/- 2.59 diopters (D) (range: -2.88 to -10.75 D) and -5.84 +/- 2.73 D (range: -3.13 to -9.38 D) for right and left eyes, respectively. The mean preoperative central corneal thickness was 548 +/- 24 microm and 547 +/- 25 microm for right and left eyes, respectively. The mean preoperative steepest K was 44.12 +/- 1.28 D and 44.41 +/- 1.27 D for right and left eyes, respectively. Corneal diameter (white-to-white) was 12 +/- 0.4 mm and 11.9 +/- 0.4 mm for right and left eyes, respectively. The mean postoperative flap thickness was 109 +/- 18 microm (range: 67 to 152 microm) and 103 +/- 15 microm (range: 65 to 151 microm) for right and left eyes, respectively. The mean postoperative flap diameter was 9.4 +/- 0.3 mm (expected mean according to the nomogram given by the company was 9.5 mm). The mean postoperative hinge chord was 4.4 +/- 0.4 mm (expected mean 4.2 mm). No interface particles were detected on slit-lamp examination. The Moria M2 90-microm single use head is safe with reasonable predictability for LASIK flap creation.

  20. 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.

  1. 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.

  2. A stringy origin of M2 brane Chern-Simons theories

    International Nuclear Information System (INIS)

    Aganagic, Mina

    2010-01-01

    We show that string duality relates M-theory on a local Calabi-Yau fourfold singularity X 4 to type IIA string theory on a Calabi-Yau threefold X 3 fibered over a real line, with RR 2-form fluxes turned on. The RR flux encodes how the M-theory circle is fibered over the IIA geometry. The theories on N D2 branes probing X 3 are the well-known quiver theories with N=2 supersymmetry in three dimensions. We show that turning on fluxes, and fibering the X 3 over a direction transverse to the branes, corresponds to turning on N=2 Chern-Simons couplings. String duality implies that, in the strong coupling limit, the N D2 branes on X 3 in this background become N M2 branes on X 4 . This provides a string theory derivation for the recently conjectured description of the M2 brane theories on Calabi-Yau fourfolds in terms of N=2 quiver Chern-Simons theories. We also provide a new N=2 Chern-Simons theory dual to AdS 4 xQ 1,1,1 . Type IIA/M-theory duality also relates IIA string theory on X 3 with only the RR fluxes turned on, to M-theory on a G 2 holonomy manifold. We show that this implies that the N M2 branes probing the G 2 manifold are described by the quiver Chern-Simons theory originating from the D2 branes probing X 3 , except that now Chern-Simons terms preserve only N=1 supersymmetry in three dimensions.

  3. Effects of amantadine on the dynamics of membrane-bound influenza A M2 transmembrane peptide studied by NMR relaxation

    Energy Technology Data Exchange (ETDEWEB)

    Cady, Sarah D.; Hong Mei [Iowa State University, Department of Chemistry (United States)], E-mail: mhong@iastate.edu

    2009-09-15

    The molecular motions of membrane proteins in liquid-crystalline lipid bilayers lie at the interface between motions in isotropic liquids and in solids. Specifically, membrane proteins can undergo whole-body uniaxial diffusion on the microsecond time scale. In this work, we investigate the {sup 1}H rotating-frame spin-lattice relaxation (T{sub 1{rho}}) caused by the uniaxial diffusion of the influenza A M2 transmembrane peptide (M2TMP), which forms a tetrameric proton channel in lipid bilayers. This uniaxial diffusion was proved before by {sup 2}H, {sup 15}N and {sup 13}C NMR lineshapes of M2TMP in DLPC bilayers. When bound to an inhibitor, amantadine, the protein exhibits significantly narrower linewidths at physiological temperature. We now investigate the origin of this line narrowing through temperature-dependent {sup 1}H T{sub 1{rho}} relaxation times in the absence and presence of amantadine. Analysis of the temperature dependence indicates that amantadine decreases the correlation time of motion from 2.8 {+-} 0.9 {mu}s for the apo peptide to 0.89 {+-} 0.41 {mu}s for the bound peptide at 313 K. Thus the line narrowing of the bound peptide is due to better avoidance of the NMR time scale and suppression of intermediate time scale broadening. The faster diffusion of the bound peptide is due to the higher attempt rate of motion, suggesting that amantadine creates better-packed and more cohesive helical bundles. Analysis of the temperature dependence of ln (T{sub 1{rho}}{sup -1}) indicates that the activation energy of motion increased from 14.0 {+-} 4.0 kJ/mol for the apo peptide to 23.3 {+-} 6.2 kJ/mol for the bound peptide. This higher activation energy indicates that excess amantadine outside the protein channel in the lipid bilayer increases the membrane viscosity. Thus, the protein-bound amantadine speeds up the diffusion of the helical bundles while the excess amantadine in the bilayer increases the membrane viscosity.

  4. 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.

  5. Uptake of BSH in M2R melanoma cells monitored by NMR spectroscopy

    International Nuclear Information System (INIS)

    Koudinova, N.; Elhanati, G.; Salomon, Y.; Bendel, P.

    2000-01-01

    The accumulation ratio of BSH, relative to that of boric acid, in M2R mouse melanoma cells, was measured using 11 B NMR of the cell extracts. The cells were incubated in growth medium for up to 24 h, in the presence of 0.8 mM boric acid and 0.25-1.5 mM BSH. The aqueous phase of the cellular extracts was re-suspended for NMR spectroscopy. The relative accumulation ratio of BSH/boric acid determined from 9 separate experiments was 0.45±0.09. (author)

  6. 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.

  7. Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

    Science.gov (United States)

    Joseph, Lauren; Thomsen, Morgane

    2017-06-30

    Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. 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.

  9. Development and evaluation of intelligent machine tools based on knowledge evolution in M2M environment

    International Nuclear Information System (INIS)

    Kim, Dong Hoon; Song, Jun Yeob; Lee, Jong Hyun; Cha, Suk Keun

    2009-01-01

    In the near future, the foreseen improvement in machine tools will be in the form of a knowledge evolution-based intelligent device. The goal of this study is to develop intelligent machine tools having knowledge-evolution capability in Machine to Machine (M2M) wired and wireless environment. The knowledge evolution-based intelligent machine tools are expected to be capable of gathering knowledge autonomously, producing knowledge, understanding knowledge, applying reasoning to knowledge, making new decisions, dialoguing with other machines, etc. The concept of the knowledge-evolution intelligent machine originated from the process of machine control operation by the sense, dialogue and decision of a human expert. The structure of knowledge evolution in M2M and the scheme for a dialogue agent among agent-based modules such as a sensory agent, a dialogue agent and an expert system (decision support agent) are presented in this paper, and work-offset compensation from thermal change and recommendation of cutting condition are performed on-line for knowledge-evolution verification

  10. Mini-magnetospheric plasma propulsion (M2P2): High speed propulsion sailing the solar wind

    International Nuclear Information System (INIS)

    Winglee, Robert; Slough, John; Ziemba, Tim; Goodson, Anthony

    2000-01-01

    Mini-Magnetospheric Plasma Propulsion (M2P2) seeks the creation of a magnetic wall or bubble (i.e. a magnetosphere) that will intercept the supersonic solar wind which is moving at 300-800 km/s. In so doing, a force of about 1 N will be exerted on the spacecraft by the spacecraft while only requiring a few mN of force to sustain the mini-magnetosphere. Equivalently, the incident solar wind power is about 1 MW while about 1 kW electrical power is required to sustain the system, with about 0.25-0.5 kg being expended per day. This nominal configuration utilizing only solar electric cells for power, the M2P2 will produce a magnetic barrier approximately 15-20 km in radius, which would accelerate a 70-140 kg payload to speeds of about 50-80 km/s. At this speed, missions to the heliopause and beyond can be achieved in under 10 yrs. Design characteristics for a prototype are also described

  11. Preliminary heat treatment of 4KhM2Fch die steel

    International Nuclear Information System (INIS)

    Leonidov, V.M.; Berezkin, Y.A.; Nikitenko, E.V.

    1986-01-01

    To improve the machinability and preparation of the structure for hardening, die steels are given a preliminary treatment which provides a reduction in hardness as a result of separation in the structure of the carbide and ferrite phases, coagulation of the carbides, and acquisition by them of a granular form and also the obtaining of fine grains and a uniform distribution of the structural constituents. The microstructure was evaluated after etching in 4% nital on an MIM-8M microscope. The 4KhM2Fch steel was given a preliminary heat treatment of normalize and anneal. It was concluded that for 4KhM2Fch steel a preliminary heat treatment of normalizing from 950 0 C with a hold of 1.5-2 h, annealing at 750-760 0 C with a hold of 2-3 h, cooling to the isothermal temperature of 670-680 0 C with a hold of 3-4 h, and further air cooling is recommended. The structure after such a heat is granular pearlite with a rating 1-2 and a hardness of 220-250 HB

  12. An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP

    International Nuclear Information System (INIS)

    Oosten, Erik M. van; Wilson, Alan A.; Stephenson, Karin A.; Mamo, David C.; Pollock, Bruce G.; Mulsant, Benoit H.; Yudin, Andrei K.; Houle, Sylvain; Vasdev, Neil

    2009-01-01

    The radioligand 3-(4-(3-[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([ 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 [ 18 F]FP-TZTP, automated using a GE TRACERlab TM FX 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 [ 18 F]fluoride (K[ 18 F]/K 222 ) in CH 3 CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [ 18 F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29±4%, with a specific activity of 138±41 GBq/μmol (3732±1109 mCi/μmol) 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

  13. Numerical modelling of the M2 tide on the northern Patagonian Shelf

    Science.gov (United States)

    Glorioso, P. D.; Simpson, J. H.

    1994-02-01

    The previously reported occurrence of tidal fronts on the Patagonian Shelf ( CARRETOet al., 1986 , Journal of Plankton Research, 8, 15-28; GLORIOSO, 1987 , Continental Shelf Research, 7, 27-34), motivated the application of a numerical model to solve the shallow-water equations with external forcing by the principal-lunar semidiurnal tide (M2) prescribed along the open boundary. The mean width of the Patagonian Shelf is comparable with a quarter wavelength of the semidiurnal tide, giving the conditions for standing wave resonance at that frequency ( WEBB, 1975 , Deep-Sea Research, 23, 1-15). The region is well recognized by its large tidal elevations and by the speed of the tidal wave changing phase very rapidly. Some of the results obtained from the modelling exercise include the mapping of the M2 tidal constants, the Simpson-Hunter stratification parameter, the mean sea surface elevation, and the distribution of tidal energy dissipation by bottom friction. These results agree qualitatively with the ship data available and with satellite infrared imagery.

  14. N = 6 superconformal Chern-Simons-matter theories, M2-branes and their gravity duals

    International Nuclear Information System (INIS)

    Aharony, Ofer; Bergman, Oren; Maldacena, Juan; Jafferis, Daniel Louis

    2008-01-01

    We construct three dimensional Chern-Simons-matter theories with gauge groups U(N) x U(N) and SU(N) x SU(N) which have explicit N = 6 superconformal symmetry. Using brane constructions we argue that the U(N) x U(N) theory at level k describes the low energy limit of N M2-branes probing a C 4 /Z k singularity. At large N the theory is then dual to M-theory on AdS 4 x S 7 /Z k . The theory also has a 't Hooft limit (of large N with a fixed ratio N/k) which is dual to type IIA string theory on AdS 4 x CP 3 . For k = 1 the theory is conjectured to describe N M2-branes in flat space, although our construction realizes explicitly only six of the eight supersymmetries. We give some evidence for this conjecture, which is similar to the evidence for mirror symmetry in d = 3 gauge theories. When the gauge group is SU(2) x SU(2) our theory has extra symmetries and becomes identical to the Bagger-Lambert theory.

  15. 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.

  16. 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.

  17. A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines.

    Science.gov (United States)

    Zhu, Wandi; Pewin, Winston; Wang, Chao; Luo, Yuan; Gonzalez, Gilbert X; Mohan, Teena; Prausnitz, Mark R; Wang, Bao-Zhong

    2017-09-10

    The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone. Compared with an intramuscular injection boost, mice receiving the MNP boost showed significantly enhanced cellular immune responses, hemagglutination-inhibition (HAI) titers, and neutralization titers. Increased frequency of antigen-specific plasma cells and long-lived bone marrow plasma cells was detected in the MNP boosted group as well, indicating that skin vaccination with 4M2e-tFliC facilitated a long-term antibody-mediated immunity. The 4M2e-tFliC MNP-boosted group also possessed enhanced protection against high lethal dose challenges against homologous A/PR/8/34 and A/Aichi/2/68 viruses and protection for a majority of immunized mice against a heterologous A/California/07/2009 H1N1 virus. High levels of M2e specific immune responses were observed in the 4M2e-tFliC MNP-boosted group as well. These results demonstrate that a skin-applied 4M2e-tFliC MNP boosting immunization to seasonal vaccine recipients may be a rapid approach for increasing the protective efficacy of seasonal vaccines in response to a significant drift seen in circulating viruses. The results also provide a new perspective for future exploration of universal influenza vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

    Science.gov (United States)

    Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

    2018-03-01

    Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

  19. 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.

  20. 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.

  1. High-spin nuclear target of 178m2Hf: creation and nuclear reaction studies

    International Nuclear Information System (INIS)

    Oganessyan, Yu.Ts.; Karamyan, S.A.; Gangrskij, Yu.P.

    1993-01-01

    A long-lived (31 years) four-quasiparticle isomer 178m 2 Hf(I,K π =16,16 + ) was produced in microweight quantities using the nuclear reaction 176 Yb( 4 He, 2n). Methods of precision chemistry and mass-separation for the purification of the produced Hf material have been developed. Thin targets of isomeric hafnium-178 on carbon backings were prepared and used in experiments on a neutron, proton and deuteron beams. First results on nuclear reactions on a high-spin exotic target were obtained. Experiments on electromagnetic interactions of the isomeric hafnium using methods of the collinear laser spectroscopy as well as of the nuclear orientation of hafnium implanted into a crystalline media were started. 11 refs.; 11 figs.; 2 tabs

  2. The anomalous amplification of M2 tide in the Taiwan Strait

    Science.gov (United States)

    Jan, Sen; Chern, Ching-Sheng; Wang, Joe; Chao, Shenn-Yu

    2004-04-01

    The complex tidal wave propagation pattern in the Taiwan Strait invites parochialism. Along the eastern (Taiwan) boundary of the strait, the anomalous amplification of M2 tide in the middle often led to the parochial view that two tidal waves coming from both ends of the strait collide in the middle, creating wave resonance. Along the western (China) boundary, one sees a southward progressive tidal wave and hence no wave collision. To reconcile, we examine a few solutions of a numerical tidal model below. Both realistic bottom bathymetry and idealized bottom topographies are used to identify dominant mechanism leading to the complex tidal wave propagation. Our process of elimination identifies the wave reflection of southward propagating tidal wave by the deep trench in the southern strait as the true cause responsible for the complex wave propagation pattern.

  3. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.

    2004-01-01

    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  4. M2, S2, K1 models of the global ocean tide

    Science.gov (United States)

    Parke, M. E.; Hendershott, M. C.

    1979-01-01

    Ocean tidal signals appear in many geophysical measurements. Geophysicists need realistic tidal models to aid in interpretation of their data. Because of the closeness to resonance of dissipationless ocean tides, it is difficult for numerical models to correctly represent the actual open ocean tide. As an approximate solution to this problem, test functions derived by solving Laplace's Tidal Equations with ocean loading and self gravitation are used as a basis for least squares dynamic interpolation of coastal and island tidal data for the constituents M2, S2, and Kl. The resulting representations of the global tide are stable over at least a ?5% variation in the mean depth of the model basin, and they conserve mass. Maps of the geocentric tide, the induced free space potential, the induced vertical component of the solid earth tide, and the induced vertical component of the gravitational field for each contituent are presented.

  5. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    International Nuclear Information System (INIS)

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E.

    1988-01-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M r 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects

  6. Comparative Analysis of the $^{178m2}$Hf Yield at Reactions with Different Projectiles

    CERN Document Server

    Karamian, S A

    2004-01-01

    The long-lived high-spin $^{178m2}$Hf $K$-isomer can be produced in nuclear reactions with different projectiles. The reaction yields and cross-sections have been measured in the series of experiments and the results are now overviewed. The systematics of isomer-to-ground state ratios are drawn and real production capabilities are estimated for the best reactions. Such a summary is relevant to the significance of the isomer studies both for the nuclear-science knowledge and for possible applications. Potential isomer applications have been earlier stressed in popular publications with probably overestimated expectations. The real possibilities are restricted in part by the production yield and by other shortcomings as well.

  7. 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.

  8. Janus field theories from non-linear BF theories for multiple M2-branes

    International Nuclear Information System (INIS)

    Ryang, Shijong

    2009-01-01

    We integrate the nonpropagating B μ gauge field for the non-linear BF Lagrangian describing N M2-branes which includes terms with even number of the totally antisymmetric tensor M IJK in arXiv:0808.2473 and for the two-types of non-linear BF Lagrangians which include terms with odd number of M IJK as well in arXiv:0809:0985. For the former Lagrangian we derive directly the DBI-type Lagrangian expressed by the SU(N) dynamical A μ gauge field with a spacetime dependent coupling constant, while for the low-energy expansions of the latter Lagrangians the B μ integration is iteratively performed. The derived Janus field theory Lagrangians are compared.

  9. Deletion of the M2-2 gene from avian metapneumovirus subgroup C impairs virus replication and immunogenicity in Turkeys.

    Science.gov (United States)

    Yu, Qingzhong; Estevez, Carlos N; Roth, Jason P; Hu, Haixia; Zsak, Laszlo

    2011-06-01

    The second matrix (M2) gene of avian metapneumovirus subgroup C (aMPV-C) contains two overlapping open reading frames (ORFs), encoding two putative proteins, M2-1 and M2-2. Both proteins are believed to be involved in viral RNA transcription or replication. To further characterize the function of the M2-2 protein in virus replication, the non-overlapping region of the M2-2 ORF was deleted from an infectious cDNA clone of the aMPV-C strain, and a viable virus was rescued by using reverse genetics technology. The recombinant virus, raMPV-C ΔM2-2, was characterized in vitro and in vivo. In Vero cells, raMPV-C ΔM2-2 replicated slightly less efficiently than the parental virus, 10-fold reduction at 48-h post-infection. The raMPV-C ΔM2-2 virus induced typical cytopathic effects (CPE) that were indistinguishable from those seen with the parental virus infection. In specific-pathogen-free (SPF) turkeys, raMPV-C ΔM2-2 was attenuated and caused no clinical signs of disease. Less than 20% of the inoculated birds shed detectable virus in tracheal tissue during the first 5 days post-infection, and no virus shedding was detected afterward. Forty percent of infected birds produced a weak antibody response at 14 days post-infection. Upon challenge with a virulent aMPV-C strain, more than 80% of the raMPV-C ΔM2-2-inoculated birds showed typical disease signs and virus shedding in tracheal tissue. These results suggest that the M2-2 protein of aMPV-C virus is not essential for virus replication in vitro, but is required for sufficient virus replication to maintain pathogenicity and immunogenicity in the natural host.

  10. 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.

  11. Preparation and photoluminescence properties of Mn2+-activated M2Si5N8 (M = Ca, Sr, Ba) phosphors

    NARCIS (Netherlands)

    Duan, C.J.; Otten, W.M.; Delsing, A.C.A.; Hintzen, H.T.J.M.

    2008-01-01

    Mn2+-doped M2Si5N8 (M=Ca, Sr, Ba) phosphors have been prepared by a solid-state reaction method at high temperature and their photoluminescence properties were investigated. The Mn2+-activated M2Si5N8 phosphors exhibit narrow emission bands in the wavelength range of 500–700 nm with peak center at

  12. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis

    NARCIS (Netherlands)

    van Bohemen, C. G.; Nabbe, A. J.; Landheer, J. E.; Grumet, F. C.; Mazurkiewicz, E. S.; Dinant, H. J.; Lionarons, R. J.; van Bodegom, P. C.; Zanen, H. C.

    1986-01-01

    The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1+M2+ and B27M1+M2-. An outbreak of dysentery (n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens

  13. A M2FS Spectroscopic Study of Low-mass Young Stars in Orion OB1

    Science.gov (United States)

    Kaleida, Catherine C.; Briceno, Cesar; Calvet, Nuria; Mateo, Mario L.; Hernandez, Jesus

    2015-01-01

    Surveys of pre-main sequence stars in the ~4-10 Myr range provide a window into the decline of the accretion phase of stars and the formation of planets. Nearby star clusters and stellar associations allow for the study of these young stellar populations all the way down to the lowest mass members. One of the best examples of nearby 4-10 Myr old stellar populations is the Orion OB1 association. The CIDA Variability Survey of Orion OB1 (CVSO - Briceño et al. 2001) has used the variability properties of low-mass pre-main-sequence (PMS) stars to identify hundreds of K and M-type stellar members of the Orion OB1 association, a number of them displaying IR-excess emission and thought to be representative of more evolved disk-bearing young stars. Characterizing these young, low-mass objects using spectroscopy is integral to understanding the accretion phase in young stars. We present preliminary results of a spectroscopic survey of candidate and confirmed Orion OB1 low-mass members taken during November 2014 and February 2014 using the Michigan/Magellan Fiber Spectrograph (M2FS), a PI instrument on the Magellan Clay Telescope (PI: M. Matteo). Target fields located in the off-cloud regions of Orion were identified in the CVSO, and observed using the low and high-resolution modes of M2FS. Both low and high-resolution spectra are needed in order to confirm membership and derive masses, ages, kinematics and accretion properties. Initial analysis of these spectra reveal many new K and M-type members of the Orion OB1 association in these low extinction, off-cloud areas. These are the more evolved siblings of the youngest stars still embedded in the molecular clouds, like those in the Orion Nebula Cluster. With membership and spectroscopic indicators of accretion we are building the most comprehensive stellar census of this association, enabling us to derive a robust estimate of the fraction of young stars still accreting at a various ages, a key constraint for the end of

  14. Human metapneumovirus M2-2 protein inhibits innate immune response in monocyte-derived dendritic cells.

    Directory of Open Access Journals (Sweden)

    Junping Ren

    Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in young children, the elderly and immunocompromised patients. Repeated hMPV infections occur throughout life. However, immune evasion mechanisms of hMPV infection are largely unknown. Recently, our group has demonstrated that hMPV M2-2 protein, an important virulence factor, contributes to immune evasion in airway epithelial cells by targeting the mitochondrial antiviral-signaling protein (MAVS. Whether M2-2 regulates the innate immunity in human dendritic cells (DC, an important family of immune cells controlling antigen presenting, is currently unknown. We found that human DC infected with a virus lacking M2-2 protein expression (rhMPV-ΔM2-2 produced higher levels of cytokines, chemokines and IFNs, compared to cells infected with wild-type virus (rhMPV-WT, suggesting that M2-2 protein inhibits innate immunity in human DC. In parallel, we found that myeloid differentiation primary response gene 88 (MyD88, an essential adaptor for Toll-like receptors (TLRs, plays a critical role in inducing immune response of human DC, as downregulation of MyD88 by siRNA blocked the induction of immune regulatory molecules by hMPV. Since M2-2 is a cytoplasmic protein, we investigated whether M2-2 interferes with MyD88-mediated antiviral signaling. We found that indeed M2-2 protein associated with MyD88 and inhibited MyD88-dependent gene transcription. In this study, we also identified the domains of M2-2 responsible for its immune inhibitory function in human DC. In summary, our results demonstrate that M2-2 contributes to hMPV immune evasion by inhibiting MyD88-dependent cellular responses in human DC.

  15. Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

    Directory of Open Access Journals (Sweden)

    JoAnn eTrial

    2013-09-01

    Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

  16. 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.

  17. Performance of Mentik Wangi rice (Oryza sativa, L.) M2 generation from gamma ray irradiation

    Science.gov (United States)

    Yunus, A.; Parjanto; Nandariyah; Wulandari, S.

    2018-03-01

    The objective of this research is to produce Mentik Wangi rice with shorter flowering age, shorter rice stem and high yield. This research was conducted in Palur Village, Mojolaban Sub-district, Sukoharjo District, from April to August 2016. This research used descriptive method, performed by observing each individual and comparing to the control average. Observational variables included plant height, total number of tillers, number of productive tillers, panicle length, number of grain per panicle, panicle density index, 1,000 filled seed weight, seed weight of cluster, flowering age and M2 mutant selection. The results showed that there were several plants indicated mutation, there were 7 plants indicate short stem mutation with height 85 cm to 97 cm. The plants which indicated short flowering age were 5 weeks after planting up to 6 weeks after planting. The mutated plants indicating of the highest number of productive tillers which were 27 up to 36. Each component result includes total number of tillers, number of productive tillers, number of grain of panicle as well as the weight of 1000 seeds in the plant indicated some mutation that has a high level of diversity in each treatment.

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

    Science.gov (United States)

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

    2016-03-01

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

  19. M2 Internal Tides and Their Observed Wavenumber Spectra from Satellite Altimetry*

    Science.gov (United States)

    Ray, R. D.; Zaron, E. D.

    2015-01-01

    A near-global chart of surface elevations associated with the stationary M2 internal tide is empirically constructed from multi-mission satellite altimeter data. An advantage of a strictly empirical mapping approach is that results are independent of assumptions about ocean wave dynamics and, in fact, can be used to test such assumptions. A disadvantage is that present-day altimeter coverage is only marginally adequate to support mapping such short-wavelength features. Moreover, predominantly north-south ground-track orientations and contamination from nontidal oceanographic variability can lead to deficiencies in mapped tides. Independent data from Cryosphere Satellite-2 (CryoSat-2) and other altimeters are used to test the solutions and show positive reduction in variance except in regions of large mesoscale variability. The tidal fields are subjected to two-dimensional wavenumber spectral analysis, which allows for the construction of an empirical map of modal wavelengths. Mode-1 wavelengths show good agreement with theoretical wavelengths calculated from the ocean's mean stratification, with a few localized exceptions (e.g., Tasman Sea). Mode-2 waves are detectable in much of the ocean, with wavelengths in reasonable agreement with theoretical expectations, but their spectral signatures grow too weak to map in some regions.

  20. Mitochondrial ROS Production Protects the Intestine from Inflammation through Functional M2 Macrophage Polarization

    Directory of Open Access Journals (Sweden)

    Laura Formentini

    2017-05-01

    Full Text Available Mitochondria are signaling hubs in cellular physiology that play a role in inflammatory diseases. We found that partial inhibition of the mitochondrial ATP synthase in the intestine of transgenic mice triggers an anti-inflammatory response through NFκB activation mediated by mitochondrial mtROS. This shielding phenotype is revealed when mice are challenged by DSS-induced colitis, which, in control animals, triggers inflammation, recruitment of M1 pro-inflammatory macrophages, and the activation of the pro-oncogenic STAT3 and Akt/mTOR pathways. In contrast, transgenic mice can polarize macrophages to the M2 anti-inflammatory phenotype. Using the mitochondria-targeted antioxidant MitoQ to quench mtROS in vivo, we observe decreased NFκB activation, preventing its cellular protective effects. These findings stress the relevance of mitochondrial signaling to the innate immune system and emphasize the potential role of the ATP synthase as a therapeutic target in inflammatory and other related diseases.

  1. 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.

  2. Wireless Infrastructure M2M Network For Distributed Power Grid Monitoring.

    Science.gov (United States)

    Gharavi, Hamid; Hu, Bin

    2017-01-01

    With the massive integration of distributed renewable energy sources (RESs) into the power system, the demand for timely and reliable network quality monitoring, control, and fault analysis is rapidly growing. Following the successful deployment of Phasor Measurement Units (PMUs) in transmission systems for power monitoring, a new opportunity to utilize PMU measurement data for power quality assessment in distribution grid systems is emerging. The main problem however, is that a distribution grid system does not normally have the support of an infrastructure network. Therefore, the main objective in this paper is to develop a Machine-to-Machine (M2M) communication network that can support wide ranging sensory data, including high rate synchrophasor data for real-time communication. In particular, we evaluate the suitability of the emerging IEEE 802.11ah standard by exploiting its important features, such as classifying the power grid sensory data into different categories according to their traffic characteristics. For performance evaluation we use our hardware in the loop grid communication network testbed to access the performance of the network.

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

    International Nuclear Information System (INIS)

    Lashkevich, Michael; Pugai, Yaroslav

    2015-01-01

    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 Φ 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 ±2k , Θ ±(2k−2) , which correspond to the spin ±(2k−1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T 2k T −2l , which generalize the famous TT̄ operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

  4. Machining tools in AISI M2 high-speed steel obtained by spray forming process

    International Nuclear Information System (INIS)

    Jesus, Edilson Rosa Barbosa de.

    2004-01-01

    The aim of the present work was the obtention of AISI M2 high-speed steel by spray forming technique and the material evaluation when used as machining tool. The obtained material was hot rolled at 50% and 72% reduction ratios, and from which it was manufactured inserts for machining tests. The performance of inserts made of the spray formed material was compared to inserts obtained from conventional and powder metallurgy (MP) processed materials. The spray formed material was chemical, physical, mechanical and microstructural characterised. For further characterisation, the materials were submitted to machining tests for performance evaluation under real work condition. The results of material characterisation highlight the potential of the spray forming technique, in the obtention of materials with good characteristics and properties. Under the current processing, hot rolling and heat treatments condition, the analysis of the results of the machining tests revealed a very similar behaviour among the tested materials. Proceeding a criterious analysis of the machining results tests, it was verified that the performance presented by the powder metallurgy material (MP) was slight superior, followed by conventional obtained material (MConv), which presented a insignificant advantage over the spray formed and hot rolled (72% reduction ratio) material. The worst result was encountered for the spray forming and hot rolled (50% reduction ratio) material that presented the highest wear values. (author)

  5. A new fluorescent test for cell vitality using calcofluor white M2R.

    Science.gov (United States)

    Fischer, J M; Peterson, C A; Bols, N C

    1985-03-01

    The fluorescent fabric-brightener dye, Calcofluor white M2R (CFW), can be used to distinguish between living and dead cells from a variety of animal and plant sources. CFW does not stain living mouse fibroblasts or trout red blood cells and stains only the cell walls in living cells from the epidermis of onion bulb scale, staminal hairs of Tradescantia, and longitudinal sections of broad bean stems and roots. Heat-killed plant or animal cells are recognized by their lightly stained cytoplasm and brightly stained nuclei. The optimum staining concentrations were very low (0.01% to 0.03%) and nontoxic. Using onion scale epidermis in which some cells had been killed by heating as a test system, and the plasmolysis-deplasmolysis rection as the ultimate test for cell vitality, results from CFW staining correctly predicted cell vitality for about 98% of the cells tested. This success rate was comparable to those for Evans blue, uranin or neutral red in this test system.

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

    Science.gov (United States)

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

    2016-04-19

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

  7. 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.

  8. Refining the microstructure of an AISI M2 tool steel by high-energy milling

    International Nuclear Information System (INIS)

    Postiglioni, R.V.; Alamino, A.E; Vurobi Junior, S.

    2009-01-01

    Samples of AISI M2 steel were produced by high-energy milling from chips of machining in Spex high energy mill, compaction and sintering of the powder obtained. The powder was analyzed by X-ray diffraction, and then compressed in discs of 8mm in diameter. The specimens have sintering at 1200 deg C for 1 hour under vacuum atmosphere, followed by annealing, quenching and tempering for 1 hour at 315 deg C and 540°C. Along with each disc, a sample of as-received steel was subjected to the same heat treatments to compare the final microstructure. After standard metallographic preparation, samples were etched with Beraha's reagent, characterized by optical microscopy, quantitative metallography, scanning electron microscopy with micro analysis and mapping by EDS, besides Vickers hardness. The steel produced by high-energy milling presented more refined carbide and better distribution in the microstructure. There was also reduction in the size of prior austenitic grains. (author)

  9. Agomelatine or ramelteon as treatment adjuncts in glioblastoma and other M1- or M2-expressing cancers.

    Science.gov (United States)

    Kast, Richard E

    2015-01-01

    The impressive but sad list of over forty clinical studies using various cytotoxic chemotherapies published in the last few years has failed to increase median survival of glioblastoma beyond two years after diagnosis. In view of this apparent brick wall, adjunctive non-cytotoxic growth factor blocking drugs are being tried, as in the CUSP9* protocol. A related theme is searching for agonists at growth inhibiting receptors. One such dataset is that of melatonin agonism at M1 or M2 receptors found on glioblastoma cells, being a negative regulator of these cells' growth. Melatonin itself is an endogenous hormone, but when used as an exogenously administered drug it has many disadvantages. Agomelatine, marketed as an antidepressant, and ramelteon, marketed as a treatment for insomnia, are currently-available melatonin receptor agonists. These melatonin receptor agonists have significant advantages over the natural ligand: longer half-life, better oral absorption, and higher affinity to melatonin receptors. They have an eminently benign side effect profile. As full agonists they should function to inhibit glioblastoma growth, as demonstrated for melatonin. A potentially helpful ancillary attribute of melatonergic agonists in glioblastoma treatment is an increase in interleukin-2 synthesis, expected, at least partially, to reverse some of the immunosuppression associated with glioblastoma.

  10. RORα Induces KLF4-Mediated M2 Polarization in the Liver Macrophages that Protect against Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Yong-Hyun Han

    2017-07-01

    Full Text Available The regulation of M1/M2 polarization in liver macrophages is closely associated with the progression of nonalcoholic steatohepatitis (NASH; however, the mechanism involved in this process remains unclear. Here, we describe the orphan nuclear receptor retinoic-acid-related orphan receptor α (RORα as a key regulator of M1/M2 polarization in hepatic residential Kupffer cells (KCs and infiltrated monocyte-derived macrophages. RORα enhanced M2 polarization in KCs by inducing the kruppel-like factor 4. M2 polarization was defective in KCs and bone-marrow-derived macrophages of the myeloid-specific RORα null mice, and these mice were susceptible to HFD-induced NASH. We found that IL-10 played an important role in connecting the function of M2 KCs to lipid accumulation and apoptosis in hepatocytes. Importantly, M2 polarization was controlled by a RORα activator, JC1-40, which improved symptoms of NASH. Our results suggest that the M2-promoting effects of RORα in liver macrophages may provide better therapeutic strategies against NASH.

  11. An M2e-based synthetic peptide vaccine for influenza A virus confers heterosubtypic protection from lethal virus challenge.

    Science.gov (United States)

    Ma, Ji-Hong; Yang, Fu-Ru; Yu, Hai; Zhou, Yan-Jun; Li, Guo-Xin; Huang, Meng; Wen, Feng; Tong, Guangzhi

    2013-07-09

    Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses. Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds' adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus. Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.

  12. NMR Determination of Protein Partitioning into Membrane Domains with Different Curvatures and Application to the Influenza M2 Peptide

    Science.gov (United States)

    Wang, Tuo; Cady, Sarah D.; Hong, Mei

    2012-01-01

    The M2 protein of the influenza A virus acts both as a drug-sensitive proton channel and mediates virus budding through membrane scission. The segment responsible for causing membrane curvature is an amphipathic helix in the cytoplasmic domain of the protein. Here, we use 31P and 13C solid-state NMR to examine M2-induced membrane curvature. M2(22–46), which includes only the transmembrane (TM) helix, and M2(21–61), which contains an additional amphipathic helix, are studied. 31P chemical shift lineshapes indicate that M2(21–61) causes a high-curvature isotropic phase to both cholesterol-rich virus-mimetic membranes and 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayers, whereas M2(22–46) has minimal effect. The lamellar and isotropic domains have distinct 31P isotropic chemical shifts, indicating perturbation of the lipid headgroup conformation by the amphipathic helix. 31P- and 13C-detected 1H T2 relaxation and two-dimensional peptide-lipid correlation spectra show that M2(21–61) preferentially binds to the high-curvature domain. 31P linewidths indicate that the isotropic vesicles induced by M2(21–61) are 10–35 nm in diameter, and the virus-mimetic vesicles are smaller than the 1,2-dimyristoyl-sn-glycero-3-phosphocholine vesicles. A strong correlation is found between high membrane curvature and weak drug-binding ability of the TM helix. Thus, the M2 amphipathic helix causes membrane curvature, which in turn perturbs the TM helix conformation, abolishing drug binding. These NMR experiments are applicable to other curvature-inducing membrane proteins such as fusion proteins and antimicrobial peptides. PMID:22385849

  13. Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

    Science.gov (United States)

    Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

    2017-09-01

    To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  14. Phase diagrams of systems of Sr2V2O7-M2V2O7 and of Ba2V2O7-M2V2O7 (M=Ca,Cd)

    International Nuclear Information System (INIS)

    Fotiev, A.A.; Zhuravlev, V.D.; Zhukov, V.P.

    1982-01-01

    Using the methods of X-ray phase and differential thermal anlyses phase equilibria in the systems Sr 2 V 2 O 7 -M 2 V 2 O 7 and Ba 2 V 2 O 7 -M 2 V 2 O 7 , where M--Ca, Cd, are studied, their phase diagrams being built. New double pyrovanadates Mosub(0.5)Srsub(1.5)Vsub(2)Osub(7) and MBaV 2 O 7 are found [ru

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

    Directory of Open Access Journals (Sweden)

    Mojtaba Sankian

    2013-05-01

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

  16. Taguchi Optimization of Cutting Parameters in Turning AISI 1020 MS with M2 HSS Tool

    Science.gov (United States)

    Sonowal, Dharindom; Sarma, Dhrupad; Bakul Barua, Parimal; Nath, Thuleswar

    2017-08-01

    In this paper the effect of three cutting parameters viz. Spindle speed, Feed and Depth of Cut on surface roughness of AISI 1020 mild steel bar in turning was investigated and optimized to obtain minimum surface roughness. All the experiments are conducted on HMT LB25 lathe machine using M2 HSS cutting tool. Ranges of parameters of interest have been decided through some preliminary experimentation (One Factor At a Time experiments). Finally a combined experiment has been carried out using Taguchi’s L27 Orthogonal Array (OA) to study the main effect and interaction effect of the all three parameters. The experimental results were analyzed with raw data ANOVA (Analysis of Variance) and S/N data (Signal to Noise ratio) ANOVA. Results show that Spindle speed, Feed and Depth of Cut have significant effects on both mean and variation of surface roughness in turning AISI 1020 mild steel. Mild two factors interactions are observed among the aforesaid factors with significant effects only on the mean of the output variable. From the Taguchi parameter optimization the optimum factor combination is found to be 630 rpm spindle speed, 0.05 mm/rev feed and 1.25 mm depth of cut with estimated surface roughness 2.358 ± 0.970 µm. A confirmatory experiment was conducted with the optimum factor combination to verify the results. In the confirmatory experiment the average value of surface roughness is found to be 2.408 µm which is well within the range (0.418 µm to 4.299 µm) predicted for confirmatory experiment.

  17. The Construal of Midwives by Pregnant Women with a Body Mass Index Greater Than or Equal to 30 kg/m2 (BMI ≥ 30 kg/m2 ): A Repertory Grid Study.

    Science.gov (United States)

    Hodgkinson, Emma L; Smith, Debbie M; Hare, Dougal Julian; Wittkowski, Anja

    2017-03-01

    To explore the construal of midwives by pregnant women with a body mass index greater than 30 kg/m 2 (BMI ≥ 30 kg/m 2 ). Ten pregnant women with a BMI ≥ 30 kg/m 2 were recruited from antenatal clinics at a maternity hospital in the North West of England. Each participant completed a repertory grid. The participants chose people to match roles including themselves, pregnant women, midwives of different BMIs and hypothetical elements. They also generated psychological constructs to describe them. Pregnant women with a BMI ≥ 30 kg/m 2 construed themselves as vulnerable and self-conscious. Some women endorsed obesity-related stereotypes for themselves and felt responsible for their weight. The midwife with a BMI 18 stereotypes. Copyright © 2016 John Wiley & Sons, Ltd. Pregnant women with a BMI ≥ 30 kg/m 2 construe themselves as vulnerable and self-conscious and perceive themselves responsible for their weight. Pregnant women with a BMI ≥ 30 kg/m 2 construe midwives with a low BMI as having an undesirable, cold, interpersonal style. Midwives with a raised BMI are construed as similar to the women, because they share the uncomfortable psychological consequences of a raised BMI. The nature of pregnant women's construal may affect their engagement and satisfaction with maternity services and midwifery care. Copyright © 2016 John Wiley & Sons, Ltd.

  18. M2 macrophages induce ovarian cancer cell proliferation via a heparin binding epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop.

    Science.gov (United States)

    Carroll, Molly J; Kapur, Arvinder; Felder, Mildred; Patankar, Manish S; Kreeger, Pamela K

    2016-12-27

    In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1 macrophages correlates with poor patient prognosis. The mechanisms driving poor tumor outcome as a result of the presence of M2 macrophages in the tumor microenvironment remain unclear and are challenging to study with current techniques. Therefore, in this study we utilized a micro-culture device previously developed by our lab to model concentrated paracrine signaling in order to address our hypothesis that interactions between M2 macrophages and ovarian cancer cells induce tumor cell proliferation. Using the micro-culture device, we determined that co-culture with M2-differentiated primary macrophages or THP-1 increased OVCA433 proliferation by 10-12%. This effect was eliminated with epidermal growth factor receptor (EGFR) or heparin-bound epidermal growth factor (HB-EGF) neutralizing antibodies and HBEGF expression in peripheral blood mononuclear cells from ovarian cancer patients was 9-fold higher than healthy individuals, suggesting a role for HB-EGF in tumor progression. However, addition of HB-EGF at levels secreted by macrophages or macrophage-conditioned media did not induce proliferation to the same extent, indicating a role for other factors in this process. Matrix metalloproteinase-9, MMP-9, which cleaves membrane-bound HB-EGF, was elevated in co-culture and its inhibition decreased proliferation. Utilizing inhibitors and siRNA against MMP9 in each population, we determined that macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased MMP9 in OVCA433, resulting in a positive feedback loop to drive HB-EGF release and increase proliferation in co-culture. Identification of multi-cellular interactions such as this may provide insight into how to most effectively control ovarian cancer progression.

  19. COMPLETE SUPPRESSION OF THE m=2/n-1 NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D

    International Nuclear Information System (INIS)

    PETTY, CC; LAHAYE, LA; LUCE, TC; HUMPHREYS, DA; HYATT, AW; PRATER, R; STRAIT, EJ; WADE, MR

    2003-01-01

    A271 COMPLETE SUPPRESSION OF THE M=2/N-1 NEOCLASSICAL TEARING MODE USING ELECTRON CYCLOTRON CURRENT DRIVE ON DIII-D. The first suppression of the important and deleterious m=2/n=1 neoclassical tearing mode (NTM) is reported using electron cyclotron current drive (ECCD) to replace the ''missing'' bootstrap current in the island O-point. Experiments on the DIII-D tokamak verify the maximum shrinkage of the m=2/n=1 island occurs when the ECCD location coincides with the q = 2 surface. The DIII-D plasma control system is put into search and suppress mode to make small changes in the toroidal field to find and lock onto the optimum position, based on real time measurements of dB θ /dt, for complete m=2/n=1 NTM suppression by ECCD. The requirements on the ECCD for complete island suppression are well modeled by the modified Rutherford equation for the DIII-D plasma conditions

  20. 25m2 target-aligned heliostat with closed-loop control

    CSIR Research Space (South Africa)

    Roos, TH

    2007-09-01

    Full Text Available system making use of a solar tracker has been developed and tested on a 1.252m target-aligned miniheliostat. A tracking accuracy of 3.3 milliradians was obtained. A good focal spot has been obtained with the 252m target-aligned research heliostat....

  1. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

    OpenAIRE

    Mi Eun Kim; Inae Jung; Jong Suk Lee; Ju Yong Na; Woo Jung Kim; Young-Ok Kim; Yong-Duk Park; Jun Sik Lee

    2017-01-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent...

  2. MicroRNA 21 Is a Homeostatic Regulator of Macrophage Polarization and Prevents Prostaglandin E2-Mediated M2 Generation

    OpenAIRE

    Wang, Zhuo; Brandt, Stephanie; Medeiros, Alexandra; Wang, Soujuan; Wu, Hao; Dent, Alexander; Serezani, C. Henrique

    2015-01-01

    Macrophages dictate both initiation and resolution of inflammation. During acute inflammation classically activated macrophages (M1) predominate, and during the resolution phase alternative macrophages (M2) are dominant. The molecular mechanisms involved in macrophage polarization are understudied. MicroRNAs are differentially expressed in M1 and M2 macrophages that influence macrophage polarization. We identified a role of miR-21 in macrophage polarization, and found that cross-talk between ...

  3. Why does the agonist [18F]FP-TZTP bind preferentially to the M2 muscarinic receptor?

    International Nuclear Information System (INIS)

    Ravasi, L.; Kiesewetter, D.O.; Shimoji, K.; Lucignani, G.; Eckelman, W.C.

    2006-01-01

    Preferential binding of FP-TZTP at the M 2 receptor in vivo led to investigation of [ 18 F]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M 2 receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M 2 selectivity. Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B max , K i , and IC 50 . In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [ 18 F]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [ 18 F]FP-TZTP from slide-bound cells that had been preincubated with [ 18 F]FP-TZTP. At equilibrium in vitro, M 2 subtype selectivity of [ 18 F]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M 2 selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M 2 subtype in the tissue region. The slower dissociation kinetics of FP-TZTP from M 2 receptors compared with the four other muscarinic receptor subtypes may be a factor in its M 2 selectivity. (orig.)

  4. Silicified conifer forests and potential mining problems in seam M2 of the Gore Lignite Measures (Miocene), Southland, New Zealand

    Energy Technology Data Exchange (ETDEWEB)

    Lindqvist, J K; Isaac, M J [New Zealand Geological Survey, Dunedin (New Zealand). Dept. of Scientific and Industrial Research

    1991-04-01

    Silicified conifer ({ital Podocarpus cf. hallii}) stumps up to 0.8 m in diameter are present at two levels in seam M2 of the Miocene Gore Lignite Measures, Mataura Coalfield, eastern Southland. The in situ stumps are believed to be the remains of forests which grew during pauses in peat accumulation, when groundwater levels were depressed as a result of climatic change or local basinal processes. Growth-ring measurements show the trees increased in radius between 0.16 and 1 mm per year. In two of six specimens, the growth-rates halved during their final 30-40 years of life; rising water levels may have resulted in less favourable growth conditions. Within the stumps, much of the wood structure is well preserved. Progressive diagenesis involved impregnation of the cell walls by silica, infilling of the cell lumens with length-slow chalcedony and opaline silica, and deposition of opal, length-fast chalcedony, and minor siderite in fractures. Radial and axial parenchyma contain coalified organic material and minor chalcedony. Filaments of wood-rotting fungi and probable root masses of epiphytes are present in some fossil wood. However, by analogy with modern Podocarpus hallii, the stumps were probably preserved for later silicification because the wood was highly resistant to fungal and bacterial decay. The stumps presumably functioned as conduits to ascending silica-saturated meteoric groundwater and water released during compaction, because of the contrasts in permeability between the vertical stumps and the surrounding peat. 25 refs., 12 figs.

  5. Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

    Science.gov (United States)

    Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

    2001-07-01

    We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  8. Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

    International Nuclear Information System (INIS)

    Wanitchang, Asawin; Wongthida, Phonphimon; Jongkaewwattana, Anan

    2016-01-01

    The M2 protein (AM2 and BM2) of influenza A and B viruses function as a proton channel essential for viral replication. They also carry a cytoplasmic tail whose functions are not fully delineated. It is currently unknown whether these proteins could be replaced functionally in a viral context. Here, we generated single-cycle influenza A viruses (scIAV-ΔHA) carrying various M2-2A-mCherry constructs in the segment 4 (HA) and evaluated their growth in complementing cells. Intriguingly, the scIAV-ΔHA carrying AM2 and that bearing BM2 grew comparably well in MDCK-HA cells. Furthermore, while the virus carrying chimeric B-AM2 in which the BM2 transmembrane fused with the AM2 cytoplasmic tail produced robust infection, the one bearing the AM2 transmembrane fused with the BM2 cytoplasmic tail (A-BM2) exhibited severely impaired growth. Altogether, we demonstrate that AM2 and BM2 are functionally interchangeable and underscore the role of compatibility between transmembrane and cytoplasmic tail of the M2 protein. -- Highlights: •Flu A M2 protein (AM2) can be functionally replaced by that of Flu B (BM2). •Both AM2 and BM2 with extended cytoplasmic tail are functional. •Compatibility between the ion channel and the cytoplasmic tail is critical for M2 function. •M2 with higher ion channel activity may augment influenza virus replication.

  9. Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication

    Energy Technology Data Exchange (ETDEWEB)

    Wanitchang, Asawin; Wongthida, Phonphimon; Jongkaewwattana, Anan, E-mail: anan.jon@biotec.or.th

    2016-11-15

    The M2 protein (AM2 and BM2) of influenza A and B viruses function as a proton channel essential for viral replication. They also carry a cytoplasmic tail whose functions are not fully delineated. It is currently unknown whether these proteins could be replaced functionally in a viral context. Here, we generated single-cycle influenza A viruses (scIAV-ΔHA) carrying various M2-2A-mCherry constructs in the segment 4 (HA) and evaluated their growth in complementing cells. Intriguingly, the scIAV-ΔHA carrying AM2 and that bearing BM2 grew comparably well in MDCK-HA cells. Furthermore, while the virus carrying chimeric B-AM2 in which the BM2 transmembrane fused with the AM2 cytoplasmic tail produced robust infection, the one bearing the AM2 transmembrane fused with the BM2 cytoplasmic tail (A-BM2) exhibited severely impaired growth. Altogether, we demonstrate that AM2 and BM2 are functionally interchangeable and underscore the role of compatibility between transmembrane and cytoplasmic tail of the M2 protein. -- Highlights: •Flu A M2 protein (AM2) can be functionally replaced by that of Flu B (BM2). •Both AM2 and BM2 with extended cytoplasmic tail are functional. •Compatibility between the ion channel and the cytoplasmic tail is critical for M2 function. •M2 with higher ion channel activity may augment influenza virus replication.

  10. Assessment of M2/ANXA5 haplotype as a risk factor in couples with placenta-mediated pregnancy complications.

    Science.gov (United States)

    Rogenhofer, Nina; Nienaber, Lara R M; Amshoff, Lea C; Bogdanova, Nadia; Petroff, David; Wieacker, Peter; Thaler, Christian J; Markoff, Arseni

    2018-01-01

    The aim of this study was to confirm the associated M2/ANXA5 carrier risk in women with placenta-mediated pregnancy complications (PMPC) and to test their male partners for such association. Further analysis evaluated the influence of maternal vs. paternal M2 alleles on miscarriage. Two hundred eighty-eight couples with preeclampsia (PE), intrauterine growth restriction (IUGR), or premature birth (PB) were recruited (n = 96 of each phenotype). The prevalence of the M2 haplotype was compared to two control cohorts. They included a group of women with a history of normal pregnancy without gestational pathology (Munich controls, n = 94) and a random population sample (PopGen controls, n = 533). Significant association of M2 haplotype and pregnancy complications was confirmed for women and for couples, where prevalence was elevated from 15.4 to 23.8% (p pregnancy complication. M2/ANXA5 appears to be a risk factor for adverse pregnancy outcomes related, but not limited to miscarriages, with similar prevalence in women and their male partners. These findings support the proposed physiological function of ANXA5 as an embryonic anticoagulant that appears deficient in contiguous specter of thrombophilia-related pregnancy complications culminating more frequently in miscarriage in a maternal M2 carrier background.

  11. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

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

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

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

    Directory of Open Access Journals (Sweden)

    Albin Jurić

    2004-12-01

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

  13. 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. © 2013.

  14. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

    Science.gov (United States)

    Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

    2017-10-01

    Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-01

    In countries where highly pathogenic avian influenza virus (HPAIV) H5N1 is endemic and controlled by vaccination, post-vaccination serological monitoring is essential to differentiate vaccinated poultry from those that are infected. The objectives of this study were to validate two experimental ELISAs that detect antibodies raised against the M2e protein of avian influenza virus that can be used for DIVA purposes. Results from the sM2e and tM2e ELISAs were compared with other conventional tests for the detection of H5N1influenza virus (virus isolation and RT-PCR) using samples collected from 16 commercial flocks in Indonesia. These comprised vaccinated layers aged between 18 and 68 weeks old that were sampled at ten-weekly intervals. A small number of sera were positive in sM2e and tM2e ELISA, 14 (0.6%) and 17 (0.7%) respectively, with low OD 420 (0.1-0.3), but only 4 sera were positive in both tests. At the flock level, the incidence of M2e positive sera was low (4%), well below previously established minimum of 40% for an HPAIV H5N1-infected flock. Conventional M and H5 gene RT-PCRs indicated that none of 16 flocks were infected at any time during the study. No virus was isolated from any of the 480 pooled swab samples, except from one, for which the combined data analysis suggest to be the result of a laboratory cross-contamination. Clinical disease, mortalities or reduction in production performance, indicative of field H5N1 challenge, were not observed either in any of the flocks. Birds from two surveyed flocks, challenged in the laboratory with an Indonesian HPAIV H5N1 developed M2e antibodies in 50% and 55% of surviving birds with OD 420 in the range of 0.35-1.47 in tM2e ELISA, confirming the validity of the criteria established for use of M2e ELISA for DIVA purposes. Overall these results showed that the tM2e ELISA could be a useful monitoring tool to ascertain freedom from H5N1 infections in vaccinated commercial poultry. Copyright © 2017 Elsevier B

  16. The effects of irradiation to 8x1026m-2 on the mechanical properties of 6061-T651 aluminum

    International Nuclear Information System (INIS)

    Alexander, D.J.

    1995-01-01

    The effects of irradiation on the mechanical properties of candidate structural materials are being examined. A key to the generation of useful neutron beams is allowing the neutrons produced in the core to escape. Therefore, an aluminum alloy has been selected for the first wall containment adjacent to the core, the Core Pressure Boundary Tube (CPBT), Alloy (6061 J651 Al 1.0Mg-0.6Si-0.3Cu-0.2Cr) with acceptable mechanical properties in unirradiated condition, low neutron cross-section, high thermal conductivity for heat removal. This alloy may also be used for the beam tubes and reflector tank. An irradiation program is underway to determine the effects of irradiation on the mechanical properties of 6061-T651 aluminium in particular the fracture toughness. This data will allow the operating lifetime of the CPBT to determined which will in turn determine its replacement schedule in the ANS. The first two capsules for the ANS Irradiation Effects program have been successfully irradiated to 10 26 and 8x10 26 m -2 (thermal flux), respectively, at a nominal irradiation temperature of 95 deg. C. The testing of the specimens of 6061-T651 aluminum has shown: 1. The yield and ultimate tensile strengths are increased by irradiation; 2. The uniform and total elongations are reduced, but useful ductility remains, even at the higher irradiation level; 3. The fracture toughness at 25 deg. C and 95 deg. C is unaffected by irradiation, but at 150 deg. C, it decreases with an increase in irradiation; 4. The tearing modulus of 6061-T651 is low in the unirradiated condition, and is reduced to very low values by irradiation. This alloy also shows a tendency for sudden unstable crack extension

  17. The feasibility phase of a community antenatal lifestyle programme [The Lifestyle Course (TLC)] for women with a body mass index (BMI)≥ 30 kg/m(2.).

    Science.gov (United States)

    Smith, Debbie M; Taylor, Wendy; Whitworth, Melissa K; Roberts, Stephen; Sibley, Colin; Lavender, Tina

    2015-02-01

    maternal obesity [body mass index (BMI)≥30kg/m(2)] is a cause for concern because of increasing rates and risk of associated complications. However, little is known about how to improve the health of women with a BMI≥30kg/m(2). a 10-week antenatal lifestyle programme (The Lifestyle Course - TLC), underpinned by behaviour change theory, was developed in a programme of research which included a prospective, multicentred, feasibility phase (n=227). Participants had a BMI≥30kg/m(2) at the start of their pregnancy, planned to deliver in two areas of Greater Manchester and were aged 18 or over. The objectives were to (1) assess the feasibility of the intervention and (2) to pilot the trial processes and outcome measures. (1) Trial intervention: only 22% of women in the feasibility phase had received gestational weight advice prior to the study. One or more TLC sessions were attended by 79% of women and 97% said they would recommend TLC to a friend due to the content suitability, perceived personal gains and extra care received. Changes to the TLC were suggested and implemented in the pilot phase. (2) Trial processes: recruitment rates (36%), retention rates (100%) and questionnaire completion rates up to one year (33%) were found. Daily general 'lifestyle' diaries and pedometers were not acceptable data collection tools (response rates of 32% and 16% respectively). However, specific food diaries were acceptable (response rates of 80-81%). The major challenge was the collection of maternal weight data at the follow-up points. the antenatal intervention (TLC) designed for this programme of work appears to suit the needs of women with a BMI≥30kg/m(2). The need for an antenatal intervention is clear from this study and also highlights reflections on effective communication with pregnant women with a BMI≥30kg/m(2). Lessons learnt for designing a future trial include effective ways to communicate with pregnant women with a BMI≥30kg/m(2). ISRCTN29860479. Copyright

  18. Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

    International Nuclear Information System (INIS)

    Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard; Schmid, Ernst; Abend, Michael; Becker, Karl-Friedrich; Apostolidis, Christos; Nikula, Tuomo K.; Kremmer, Elisabeth

    2005-01-01

    Radioimmunotherapy with α-particle-emitting nuclides, such as 213 Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213 Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213 Bi-d9MAb targeting d9-E-cadherin and 213 Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213 Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213 Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213 Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of α-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213 Bi-d9MAb compared with unspecific 213 Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213 Bi-immunoconjugates per cell exceeded 2 x 10 4 , most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213 Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. 213 Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells

  19. Cell death triggered by alpha-emitting {sup 213}Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Schmid, Ernst [National Research Center for Environment and Health, Institute of Radiation Biology, GSF, Neuherberg (Germany); Abend, Michael [German Armed Forces, Institute of Radiobiology, Munich (Germany); Becker, Karl-Friedrich [Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); National Research Center for Environment and Health, Institute of Pathology, GSF, Neuherberg (Germany); National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany); Apostolidis, Christos; Nikula, Tuomo K. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Kremmer, Elisabeth [National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany)

    2005-03-01

    Radioimmunotherapy with {alpha}-particle-emitting nuclides, such as{sup 213}Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by {sup 213}Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of {sup 213}Bi-d9MAb targeting d9-E-cadherin and {sup 213}Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as {sup 213}Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and {sup 213}Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with {sup 213}Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of {alpha}-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific {sup 213}Bi-d9MAb compared with unspecific {sup 213}Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound {sup 213}Bi-immunoconjugates per cell exceeded 2 x 10{sup 4}, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by {sup 213}Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. {sup 213}Bi-immunoconjugates seem

  20. TITERS OF ANTIBODIES TO Β1-ADRENOCEPTOR AND M2 CHOLINERGIC RECEPTORS IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS WITHOUT AN ORGANIC CARDIOVASCULAR DISEASE AND THEIR POSSIBLE CLINICAL SIGNIFICANCE

    Directory of Open Access Journals (Sweden)

    M. M. Rogova

    2012-01-01

    Full Text Available Aim. To identify the most promising epitopes that simulate various sites β1-adrenergic and M2-cholinergic receptors, and to evaluate their possible contribution to the development and maintenance of cardiac arrhythmias, particularly idiopathic ventricular arrhythmia. Material and methods. Patients with ventricular arrhythmias without organic cardiovascular disease (the study group; n=70 were included in the study. The control group consisted of 20 healthy volunteers. Evaluation of levels of antibodies to antigenic determinants, modeling various sites β1-adrenergic and M2-cholinergic performed in all patients. Causal treatment with clarithromycin and valacyclovir performed in part of patients. Results. Antibodies to different peptide sequences of β1-adrenergic and M2-cholinergic receptors have been identified in 25% of main group patients. A direct correlation between the frequency of episodes of ventricular tachycardia and IgG levels to MRI-MRIV (p=0.02 revealed. Increase in titre of antibodies to β1-adrenoceptors, to a peptide sequence β8 (p=0.02, and lower titers of antibodies to the M2 acetylcholine receptor — chimera MRI-MRIV IgM (p=0.06 and ARI-MRIV IgM (p=0.07 were observed when assessing the efficacy of the therapy in the causal dynamics in the group of "untreated" patients. IgG titer reduction of ARI-MRIV (p=0.02, which is 4 times out of 10 with reduction of ventricular ectopic activity , recorded after valacyclovir therapy. Clarithromycin therapy on the level of antibodies exerted no significant effect. Conclusion. Possible involvement of antibodies to β1-adrenoceptor and M2-cholinergic receptors in the development of idiopathic ventricular arrhythmias demonstrated. The relationship between the frequency of episodes of ventricular tachycardia and levels of antibody titers to M2-cholinergic receptors found. Attempt of causal treatment, depending on the possible mechanisms of the autoimmune process is executed. Further studies to

  1. PRECIPITATION BEHAVIOR OF M2N IN A HIGH-NITROGEN AUSTENITIC STAINLESS STEEL DURING ISOTHERMAL AGING

    Institute of Scientific and Technical Information of China (English)

    F. Shi; L.J. Wang; W.F. Cui; C.M. Liu

    2007-01-01

    The precipitation behavior of M2N and the microstructural evolution in a Cr-Mn austenitic stainless steel with a high nitrogen content of 0.43mass% during isothermal aging has been investigated using optical microscopy (OM), scanning electron microscopy ( SEM), and transmission electron microscopy (TEM). The aging treatments have led to the decomposition of nitrogen supersaturated austenitic matrix through discontinuous cellular precipitation. The precipitated cells comprise alternate lamellae of M2N precipitate and austenitic matrix. This kind of precipitate morphology is similar to that of pearlite. However, owing to the non-eutectoidic mechanism of the reaction, the growth characteristic of the cellular precipitates is different from that of pearlite in Fe-C binary alloys. M2N precipitate in the cell possesses a hexagonal crystal structure with the parameters a=0.4752nm and c=0.4429nm, and the orientation relationship between the MN precipitates and austenite determined from the SADP is [01110]M2N// [101]γ,[2-1-10]M2N// [010]γ.

  2. Avian metapneumovirus M2:2 protein inhibits replication in Vero cells: modification facilitates live vaccine development.

    Science.gov (United States)

    Clubbe, Jayne; Naylor, Clive J

    2011-11-28

    Throughout the world, avian metapneumovirus (AMPV) infection of subtype A is principally controlled by two live vaccines both derived from UK field strain #8544. Improvements of those vaccines by use of reverse genetics technology was found to be hampered by the inability of #8544 to replicate in the commonly exploited Vero cell based reverse genetics system. A systematic reverse genetics based genome modification of a DNA copy of #8544, employing sequence data from a Vero grown, #8544 derived, live vaccine; was used to determine mutations required to facilitate virus recovery and replication in Vero cells. This identified a single coding substitution in the M2:2 reading frame as responsible. Furthermore, ablation of M2:2 was found to elicit the same outcome. M2:2 sequence analysis of seven AMPVs found Vero cell adaption to be associated with non similar amino acid changes in M2:2. The study shows that M2:2 modification of field virus #8544 will enable research leading to improved vaccines. This may have more general application to other AMPV field strains. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Dynamic Resource Allocation and Access Class Barring Scheme for Delay-Sensitive Devices in Machine to Machine (M2M) Communications.

    Science.gov (United States)

    Li, Ning; Cao, Chao; Wang, Cong

    2017-06-15

    Supporting simultaneous access of machine-type devices is a critical challenge in machine-to-machine (M2M) communications. In this paper, we propose an optimal scheme to dynamically adjust the Access Class Barring (ACB) factor and the number of random access channel (RACH) resources for clustered machine-to-machine (M2M) communications, in which Delay-Sensitive (DS) devices coexist with Delay-Tolerant (DT) ones. In M2M communications, since delay-sensitive devices share random access resources with delay-tolerant devices, reducing the resources consumed by delay-sensitive devices means that there will be more resources available to delay-tolerant ones. Our goal is to optimize the random access scheme, which can not only satisfy the requirements of delay-sensitive devices, but also take the communication quality of delay-tolerant ones into consideration. We discuss this problem from the perspective of delay-sensitive services by adjusting the resource allocation and ACB scheme for these devices dynamically. Simulation results show that our proposed scheme realizes good performance in satisfying the delay-sensitive services as well as increasing the utilization rate of the random access resources allocated to them.

  4. Acetylcholine Attenuates Hypoxia/ Reoxygenation-Induced Mitochondrial and Cytosolic ROS Formation in H9c2 Cells via M2 Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Yi Miao

    2013-02-01

    Full Text Available Background: The anti-infammatory and cardioprotective effect of acetylcholine (ACh has been reported; nevertheless, whether and how ACh exhibits an antioxidant property against ischemia/reperfusion (I/R-induced oxidative stress remains obscure. Methods: In the present study, H9c2 rat cardiomyocytes were exposed to hypoxia/reoxygenation (H/R to mimic I/R injury. We estimated intracellular different sources of reactive oxygen species (ROS by measuring mitochondrial ROS (mtROS, mitochondrial DNA (mtDNA copy number, xanthine oxidase (XO and NADPH oxidase (NOX activity and expression of rac 1. Cell injury was determined by lactate dehydrogenase (LDH release and cleaved caspase-3 expression. The siRNA transfection was performed to knockdown of M2 acetylcholine receptor (M2 AChR expression. Results: 12-h hypoxia followed by 2-h reoxygenation resulted in an abrupt burst of ROS in H9c2 cells. Administration of ACh reduced the levels of ROS in a concentration-dependent manner. Compared to the H/R group, ACh decreased mtROS, recovered mtDNA copy number, diminished XO and NOX activity, rac 1 expression as well as cell injury. Co- treatment with atropine rather than hexamethonium abolished the antioxidant and cardioprotective effect of ACh. Moreover, knockdown of M2 AChR by siRNA showed the similar trends as atropine co-treatment group. Conclusions: ACh inhibits mitochondria-, XO- and NOX-derived ROS production thus protecting H9c2 cells against H/R-induced oxidative stress, and these benefcial effects are mainly mediated by M2 AChR. Our findings suggested that increasing ACh release could be a potential therapeutic strategy for treatment and prevention of I/R injury.

  5. Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla.

    Science.gov (United States)

    Schreiner, Simon J; Kirchner, Thomas; Wyss, Michael; Van Bergen, Jiri M G; Quevenco, Frances C; Steininger, Stefanie C; Griffith, Erica Y; Meier, Irene; Michels, Lars; Gietl, Anton F; Leh, Sandra E; Brickman, Adam M; Hock, Christoph; Nitsch, Roger M; Pruessmann, Klaas P; Henning, Anke; Unschuld, Paul G

    2016-12-01

    Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 ± 5.7 years, Mini-Mental State Examination 29.4 ± 4.1). The Verbal Learning and Memory Test (VLMT) was administered as part of a neuropsychological battery for assessment of episodic memory performance. Significant differences between PCP gray and white matter could be observed for glutamate-glutamine (p = 0.001), choline (p = 0.01), and myo-inositol (p = 0.02). Low Verbal Learning and Memory Test performance was associated with high N-acetylaspartate in PCP gray matter (p = 0.01) but not in PCP white matter. Our data suggest that subtle decreases in episodic memory performance in the elderly may be associated with increased levels of N-acetylaspartate as a reflection of increased mitochondrial energy capacity in PCP gray matter. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Selective-field-ionization dynamics of a lithium m=2 Rydberg state: Landau-Zener model versus quantal approach

    International Nuclear Information System (INIS)

    Foerre, M.; Hansen, J.P.

    2003-01-01

    The selective-field-ionization (SFI) dynamics of a Rydberg state of lithium with magnetic quantum number m=2 is studied in detail based on two different theoretical models: (1) a close coupling integration of the Schroedinger equation and (2) the multichannel (incoherent) Landau-Zener (MLZ) model. The m=2 states are particularly interesting, since they define a border zone between fully adiabatic (m=0,1) and fully diabatic (m>2) ionization dynamics. Both sets of calculations are performed up to, and above, the classical ionization limit. It is found that the MLZ model is excellent in the description of the fully diabatic dynamics while certain discrepancies between the time dependent quantal amplitudes appear when the dynamics become involved. Thus, in this region, the analysis of experimental SFI spectra should be performed with care

  7. CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection.

    Science.gov (United States)

    van den Bosch, Thierry P P; Caliskan, Kadir; Kraaij, Marina D; Constantinescu, Alina A; Manintveld, Olivier C; Leenen, Pieter J M; von der Thüsen, Jan H; Clahsen-van Groningen, Marian C; Baan, Carla C; Rowshani, Ajda T

    2017-01-01

    During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples in 25 heart transplant recipients experiencing acute cellular rejection. Additionally, 33 healthy individuals served as control. Using histology, immunohistochemistry, confocal laser scan microscopy, and digital imaging expression of CD14, CD16, CD56, CD68, CD80, and CD163 were explored to define monocyte and macrophage tissue profiles during rejection. Fibrosis was investigated using Sirius Red stainings of rejection, non-rejection, and 1-year biopsies. Expression of co-stimulatory and migration-related molecules on circulating monocytes, and production potential for pro- and anti-inflammatory cytokines were studied using flow cytometry. At tissue level, striking CD16+ monocyte infiltration was observed during rejection ( p  rejection compared to barely present CD68+CD80+ M1 macrophages. Rejection was associated with severe fibrosis in 1-year biopsies ( p  rejection status, decreased frequencies of circulating CD16+ monocytes were found in patients compared to healthy individuals. Rejection was reflected by significantly increased CD54 and HLA-DR expression on CD16+ monocytes with retained cytokine production potential. CD16+ monocytes and M2 macrophages hallmark the correlates of heart transplant acute cellular rejection on tissue level and seem to be associated with fibrosis in the long term.

  8. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

    International Nuclear Information System (INIS)

    Jang, Ji-Young; Lee, Jong-Kuen; Jeon, Yoon-Kyung; Kim, Chul-Woo

    2013-01-01

    Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

  9. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Sofia Edin

    Full Text Available High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC. Tumor associated macrophages (TAMs play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages and tumor promoting (M2 macrophages activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI screening status and the CpG island methylator phenotype (CIMP. A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2 (also denoted iNOS as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+ or M2 (CD163(+ phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+ and CD163(+ cells (P<0.0001. A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001 and CD163 (P<0.0001 infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2(+ cells had a significantly better prognosis than those infiltrated by few NOS2(+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.

  10. Collection and sharing of medical information and medical intelligence (M2I) in NATO: a transversal survey.

    Science.gov (United States)

    Bedubourg, Gabriel; Wiik, H; Queyriaux, B; Lausund, P; Meynard, J-B

    2018-04-06

    There is a requirement for adequate medical expertise to be available throughout the range of potential future operations involving members of the North Atlantic Treaty Organization (NATO). The aim of this study was to assess the collection and sharing of medical intelligence and medical information (M2I) by NATO Nations, Partner Nations and NATO Command Structure and NATO Force Structure Headquarters (NCS/NFS HQs). A transversal survey was conducted between December 2014 and March 2015 using a survey form on M2I sent to NATO Nations and Partnership for Peace (PfP) Nations as well as NCS/NFS HQs. Correctly completed responses were received from 15/40 (37.5%) of the possible NATO and PfP Nations (37.5%) and 7/8 (87.5%) of the NCS/NFS HQs (100.0%). Deficiencies in the collection of M2I data were found due to lack of specific doctrines, networks, tools, structures and organisation. The survey provided an indication even though the participation rate was low for Nations. Part of the problem is thought to be that medical information and medical intelligence often lie in different chains of command. Future directions for this research could include studying the possibilities of a new specific information technology (IT) system to collect and to share M2I. Collection and sharing of M2I within the NATO/PfP community requires facilitation in order to strengthen the basis for decision-making and force health protection. The development of a dedicated NATO IT system may be a precondition for the implementation of an efficient M2I network. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

    Directory of Open Access Journals (Sweden)

    Kotal M

    2008-08-01

    Full Text Available Abstract Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP. However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is

  12. Bariatric Surgery for Type 2 Diabetes Mellitus in Patients with BMI <30 kg/m2: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Attit Baskota

    Full Text Available The role of bariatric surgery in non-obese patients with type 2 diabetes (T2DM remains unclear, and its use in clinical practice is controversial. We conducted a systemic review and meta-analysis to investigate the metabolic changes after surgical treatment in diabetic patients with body mass index (BMI <30 kg/m2.We conducted a comprehensive search in MEDLINE (PubMed, EMBASE and the Cochrane Library of published articles from January 2000 to April 2013 reporting the clinical outcome changes in various metabolic outcomes in diabetic patients with BMI <30 kg/m2.Ten prospective studies including 290 patients were included in the meta-analysis. Bariatric surgery led to an overall 2.79 kg/m2 [95%CI 2.05~3.53, P<0.00001] reduction in BMI, a 1.88%[95%CI 1.32~2.43, P<0.00001] reduction in glycosylated hemoglobin, a 3.70 mmol/L [95%CI, 1.93~5.47, P<0.00001] reduction in fasting blood glucose, a 6.69 mmol/L [95%CI, 2.29~11.08, P=0.003] reduction in postprandial glucose, anda 3.37 [95%CI 0.55~6.18, P=0.02] reduction in homeostasis model assessment of insulin resistance (HOMA-IR. After surgical treatment, 76.2% of the patients were insulin free, and 61.8% patients were off medication. In total, 90(42.4%, 10(37% and 34(37.2% patients had post-surgical HbA1c levels of <6%,<6.5% and<7%, respectively. No deaths were observed in the included studies, and the major complication rate was 6.2%.Based on the currently available data, bariatric surgery might improve glycemic control and weight loss in a very limited range with a doubled surgical complication rate in drug-refractory T2DM patients with BMI <30 kg/m2. It remains too premature to suggest bariatric surgery for non-obese T2DM patients.

  13. Influence of quenching parameters in the carbides presence in the AISI M2 high speed steel

    International Nuclear Information System (INIS)

    Magalhaes, A.S.; Maria, G.G.B; Martins, S.C.S.; Lopes, W.; Correa, E.C.S.; Bezerra, A.C.S.

    2014-01-01

    The main characteristic of high speed steels, besides maintaining high hardness at room temperature, is the ability of retain hardness when subjected to high temperatures and high cutting speeds. The high percentage of alloying elements in these steels allows the development of complex carbides, acquiring a high hardness by heat treatment. The aim of this study is to evaluate the effects of quenching parameters in the volumetric fraction of carbides by semi-quantitative metallography and of retained austenite by X-ray diffraction. It has been observed that, in general, the increase in the soaking time and in the austenitizing temperature resulted in the reduction of the amount of carbides and in an increase in the amount of retained austenite in the martensitic matrix. (author)

  14. M1 Macrophages but Not M2 Macrophages Are Characterized by Upregulation of CRP Expression via Activation of NFκB: a Possible Role for Ox-LDL in Macrophage Polarization.

    Science.gov (United States)

    Kaplan, Marielle; Shur, Anna; Tendler, Yvgeny

    2018-04-23

    Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression. M1/M2 macrophage polarization was validated using THP-1 macrophages. CRP mRNA and protein expression were determined using real-time PCR and immunohistochemistry. Involvement of NFκB was determined by nuclear translocation of p50 subunit and the use of NFκB inhibitor. Involvement of oxidative stress in macrophage phenotypes induction was studied using oxidized-LDL (Ox-LDL) and antioxidants. M1 macrophages were characterized by elevated CRP mRNA expression (by 67%), CRP protein levels (by 108%), and upregulation of NFκB activation compared to control, but these features were not shared by M2 macrophages. Macrophages incubation with Ox-LDL led to a moderate M1 phenotype combined with a M2 phenotype, correlated with increased CRP mRNA expression. Antioxidants inhibited by up to 86% IL6 expression but did not significantly affect IL10 secretion. Antioxidants significantly inhibited CRP expression in M1 macrophages, but not in M2 macrophages. Elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFκB activation. Oxidative stress could be one of the endogenous triggers for macrophage activation to a mixed M1 and M2 phenotype, in association with increased expression of CRP.

  15. Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe

    DEFF Research Database (Denmark)

    Nagirnaja, Liina; Nõmmemees, Diana; Rull, Kristiina

    2015-01-01

    and recurrent pregnancy loss (RPL), however with inconclusive results. STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia...... compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%). CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic...

  16. Nanoscale clusters in the high performance thermoelectric AgPb{sub m}SbTe{sub m+2}

    Energy Technology Data Exchange (ETDEWEB)

    Lin, H; Bozin, E S; Billinge, S J.L.; Quarez, Eric; Kanatzidis, M G [Department of Physics and Astronomy, Michigan State University, East Lansing, Michigan 48824 (United States); Department of Chemistry, Michigan State University, East Lansing, Michigan 48824 (United States)

    2005-11-01

    The local structure of the AgPb{sub m}SbTe{sub m+2} series of thermoelectric materials has been studied using the atomic pair distribution function (PDF) method. Three candidate-models were attempted for the structure of this class of materials using either a one- or a two-phase modeling procedure. Combining modeling the PDF with HRTEM data we show that AgPb{sub m}SbTe{sub m+2} contains nanoscale inclusions with composition close to AgPb{sub 3}SbTe{sub 5} randomly embedded in a PbTe matrix.

  17. Molecular association of glucose-6-phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehydrogenase in cancer cells

    International Nuclear Information System (INIS)

    Das, Mahua R.; Bag, Arup K.; Saha, Shekhar; Ghosh, Alok; Dey, Sumit K.; Das, Provas; Mandal, Chitra; Ray, Subhankar; Chakrabarti, Saikat; Ray, Manju; Jana, Siddhartha S.

    2016-01-01

    For a long time cancer cells are known for increased uptake of glucose and its metabolization through glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key regulatory enzyme of this pathway and can produce ATP through oxidative level of phosphorylation. Previously, we reported that GAPDH purified from a variety of malignant tissues, but not from normal tissues, was strongly inactivated by a normal metabolite, methylglyoxal (MG). Molecular mechanism behind MG mediated GAPDH inhibition in cancer cells is not well understood. GAPDH was purified from Ehrlich ascites carcinoma (EAC) cells based on its enzymatic activity. GAPDH associated proteins in EAC cells and 3-methylcholanthrene (3MC) induced mouse tumor tissue were detected by mass spectrometry analysis and immunoprecipitation (IP) experiment, respectively. Interacting domains of GAPDH and its associated proteins were assessed by in silico molecular docking analysis. Mechanism of MG mediated GAPDH inactivation in cancer cells was evaluated by measuring enzyme activity, Circular dichroism (CD) spectroscopy, IP and mass spectrometry analyses. Here, we report that GAPDH is associated with glucose-6-phosphate isomerase (GPI) and pyruvate kinase M2 (PKM2) in Ehrlich ascites carcinoma (EAC) cells and also in 3-methylcholanthrene (3MC) induced mouse tumor tissue. Molecular docking analyses suggest C-terminal domain preference for the interaction between GAPDH and GPI. However, both C and N termini of PKM2 might be interacting with the C terminal domain of GAPDH. Expression of both PKM2 and GPI is increased in 3MC induced tumor compared with the normal tissue. In presence of 1 mM MG, association of GAPDH with PKM2 or GPI is not perturbed, but the enzymatic activity of GAPDH is reduced to 26.8 ± 5 % in 3MC induced tumor and 57.8 ± 2.3 % in EAC cells. Treatment of MG to purified GAPDH complex leads to glycation at R399 residue of PKM2 only, and changes the secondary structure of the protein complex. PKM2

  18. SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2017-06-01

    Full Text Available Sodium-glucose cotransporter (SGLT 2 inhibitors increase urinary glucose excretion (UGE, leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obesity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO mice. C57BL/6J mice were pair-fed a high-fat diet (HFD or a HFD with empagliflozin for 16 weeks. Empagliflozin administration increased UGE in the DIO mice, whereas it suppressed HFD-induced weight gain, insulin resistance, and hepatic steatosis. Moreover, empagliflozin shifted energy metabolism towards fat utilization, elevated AMP-activated protein kinase and acetyl-CoA carbolxylase phosphorylation in skeletal muscle, and increased hepatic and plasma fibroblast growth factor 21 levels. Importantly, empagliflozin increased energy expenditure, heat production, and the expression of uncoupling protein 1 in brown fat and in inguinal and epididymal white adipose tissue (WAT. Furthermore, empagliflozin reduced M1-polarized macrophage accumulation while inducing the anti-inflammatory M2 phenotype of macrophages within WAT and liver, lowering plasma TNFα levels and attenuating obesity-related chronic inflammation. Thus, empagliflozin suppressed weight gain by enhancing fat utilization and browning and attenuated obesity-induced inflammation and insulin resistance by polarizing M2 macrophages in WAT and liver.

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

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Dibas, Mohammed I; Lester, Henry A

    2007-01-01

    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...

  20. Gaz de France first quarter 2007 sales: an 11 per cent drop due to an exceptionally warm winter: a 1.3 per cent increase on an average-climate basis. Non-audited IFRS data

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    Paris, May 14 2007 - For the first quarter 2007, Gaz de France Group posted euro 9,053 million in consolidated sales. This 11 per cent decrease on the same period in 2006 is a direct result of the extremely warm weather conditions in France and Europe this winter. In contrast, under average climate conditions sales improved by 1.3 per cent. In France, where the winter of 2006/2007 was the warmest in fifty years, sales were impacted by 18 billion kWh in the quarter compared to a quarter with average-climate conditions and 32 billion kWh compared to the first quarter 2006 which, in contrast, was colder than normal. The impact of the weather had similar effects on sales outside France. The highly unusual weather conditions also had an indirect impact on the market and, consequently, on both gas production and the arbitrage activities. Not withstanding these effects, the Group continued to consolidate its position in foreign markets, with sales outside France reaching euro 3,341 million. The share of sales outside France increased by 3 points in the first quarter of 2007 versus first quarter 2006 to 37 per cent as at end March 2007. The group reiterates the 2007 financial objective as presented at the full year 2006 results: '2007 will be a year of consolidation and the EBITDA should be in line with that of 2006'.

  1. Gaz de France first quarter 2007 sales: an 11 per cent drop due to an exceptionally warm winter: a 1.3 per cent increase on an average-climate basis. Non-audited IFRS data

    International Nuclear Information System (INIS)

    2007-01-01

    Paris, May 14 2007 - For the first quarter 2007, Gaz de France Group posted euro 9,053 million in consolidated sales. This 11 per cent decrease on the same period in 2006 is a direct result of the extremely warm weather conditions in France and Europe this winter. In contrast, under average climate conditions sales improved by 1.3 per cent. In France, where the winter of 2006/2007 was the warmest in fifty years, sales were impacted by 18 billion kWh in the quarter compared to a quarter with average-climate conditions and 32 billion kWh compared to the first quarter 2006 which, in contrast, was colder than normal. The impact of the weather had similar effects on sales outside France. The highly unusual weather conditions also had an indirect impact on the market and, consequently, on both gas production and the arbitrage activities. Not withstanding these effects, the Group continued to consolidate its position in foreign markets, with sales outside France reaching euro 3,341 million. The share of sales outside France increased by 3 points in the first quarter of 2007 versus first quarter 2006 to 37 per cent as at end March 2007. The group reiterates the 2007 financial objective as presented at the full year 2006 results: '2007 will be a year of consolidation and the EBITDA should be in line with that of 2006'

  2. Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

    Science.gov (United States)

    Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

    2017-09-01

    Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Population pharmacokinetics of oxaliplatin (85 mg/m(2)) in combination with 5-fluorouracil in patients with advanced colorectal cancer

    NARCIS (Netherlands)

    Kho, Y.H.; Jansman, F.G.A.; Prins, N.H.; Neef, C.; Brouwers, J.R.B.J.

    Pharmacokinetic (PK) studies of oxaliplatin, using a dose regimen of 85mg/m(2) are lacking. A PK model may be used in future studies to investigate the relationship between pharmacokinetics and dose limiting toxicity. The purpose of this study was to construct a population PK model to describe

  4. A Collaboration-Oriented M2M Messaging Mechanism for the Collaborative Automation between Machines in Future Industrial Networks

    Directory of Open Access Journals (Sweden)

    Zhaozong Meng

    2017-11-01

    Full Text Available Machine-to-machine (M2M communication is a key enabling technology for industrial internet of things (IIoT-empowered industrial networks, where machines communicate with one another for collaborative automation and intelligent optimisation. This new industrial computing paradigm features high-quality connectivity, ubiquitous messaging, and interoperable interactions between machines. However, manufacturing IIoT applications have specificities that distinguish them from many other internet of things (IoT scenarios in machine communications. By highlighting the key requirements and the major technical gaps of M2M in industrial applications, this article describes a collaboration-oriented M2M (CoM2M messaging mechanism focusing on flexible connectivity and discovery, ubiquitous messaging, and semantic interoperability that are well suited for the production line-scale interoperability of manufacturing applications. The designs toward machine collaboration and data interoperability at both the communication and semantic level are presented. Then, the application scenarios of the presented methods are illustrated with a proof-of-concept implementation in the PicknPack food packaging line. Eventually, the advantages and some potential issues are discussed based on the PicknPack practice.

  5. 78 FR 69778 - Adjustments to Limitations on Designated School Official Assignment and Study by F-2 and M-2...

    Science.gov (United States)

    2013-11-21

    ... to attract the best and brightest international students to study in our schools. Access of F-2 or M... change existing regulations allowing full-time study by children in elementary or secondary school... best and brightest international students to study in our schools. The ability of F-2 or M-2...

  6. On thermodynamics of charged AdS black holes in extended phases space via M2-branes background

    International Nuclear Information System (INIS)

    Chabab, M.; Masmar, K.; El Moumni, H.

    2016-01-01

    Motivated by a recent work on asymptotically AdS 4 black holes in M-theory, we investigate both thermodynamics and the thermodynamical geometry of Reissner-Nordstrom-AdS black holes from M2-branes. More precisely, we study AdS black holes in AdS 4 x S 7 , with the number of M2-branes interpreted as a thermodynamical variable. In this context, we calculate various thermodynamical quantities including the chemical potential, and examine their phase transitions along with the corresponding stability behaviors. In addition, we also evaluate the thermodynamical curvatures of the Weinhold, Ruppeiner, and Quevedo metrics for M2-branes geometry to study the stability of such a black object. We show that the singularities of these scalar curvature's metrics reproduce similar stability results to those obtained by the phase transition diagram via the heat capacities in different ensembles either when the number of the M2 branes or the charge is held fixed. Also, we note that all results derived in Belhaj et al. (Eur Phys J C 76(2):73, 2016) are recovered in the limit of the vanishing charge. (orig.)

  7. Draft Genome Sequence of Bacillus mycoides M2E15, a Strain Isolated from the Endosphere of Potato

    NARCIS (Netherlands)

    Yi, Yanglei; de Jong, Anne; Spoelder, Jan; Elzenga, J Theo M; van Elsas, Jan Dirk; Kuipers, Oscar P

    2016-01-01

    We present the draft genome sequence of Bacillus mycoides M2E15, a bacterium isolated from potato endosphere. Analysis of the 6.08-Mbp draft genome sequence identified 6,386 protein-encoding sequences, including potential plant growth promoting genes. Specifically, genes for proteins involved in

  8. Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics

    Directory of Open Access Journals (Sweden)

    Yuping Ren

    2017-12-01

    Full Text Available Human metapneumovirus (hMPV is a leading cause of lower respiratory infection in pediatric populations globally. This study examined proteomic profile changes in A549 cells infected with hMPV and two attenuated mutants with deleted PDZ domain-binding motif(s in the M2-2 protein. These motifs are involved in the interruption of antiviral signaling, namely the interaction between the TNF receptor associated factor (TRAF and mitochondrial antiviral-signaling (MAVS proteins. The aim of this study was to provide insight into the overall and novel impact of M2-2 motifs on cellular responses via an unbiased comparison. Tandem mass tagging, stable isotope labeling, and high-resolution mass spectrometry were used for quantitative proteomic analysis. Using quantitative proteomics and Venn analysis, 1248 common proteins were detected in all infected samples of both technical sets. Hierarchical clustering of the differentiated proteome displayed distinct proteomic signatures that were controlled by the motif(s. Bioinformatics and experimental analysis confirmed the differentiated proteomes, revealed novel cellular biological events, and implicated key pathways controlled by hMPV M2-2 PDZ domain-binding motif(s. This provides further insight for evaluating M2-2 mutants as potent vaccine candidates.

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

    Directory of Open Access Journals (Sweden)

    Virginie Desestret

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

  10. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation.

    Science.gov (United States)

    Jacoby, Meagan A; Virgin, Herbert W; Speck, Samuel H

    2002-02-01

    Infection of mice with murine gammaherpesvirus 68 (gamma HV68; also referred to as MHV68) provides a tractable small-animal model with which to address the requirements for the establishment and maintenance of gammaherpesvirus infection in vivo. The M2 gene of gamma HV68 is a latency-associated gene that encodes a protein lacking discernible homology to any known viral or cellular proteins. M2 gene transcripts have been detected in latently infected splenocytes (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999; H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999) and peritoneal exudate cells (H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999), as well as in a latently gamma HV68-infected B-lymphoma cell line (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999). Here we describe the generation of gamma HV68 mutants with disruptions in the M2 gene. Mutation of the M2 gene did not affect the ability of the virus to replicate in tissue culture, nor did it affect gamma HV68 virulence in B6.Rag1 deficient mice. However, we found that M2 was differentially required for acute replication in vivo. While mutation of M2 did not affect acute phase of virus replication in the lungs of mice following intranasal inoculation, acute-phase virus replication in the spleen was decreased compared to that of the wild-type and marker rescue viruses following intraperitoneal inoculation. Upon intranasal inoculation, M2 mutant viruses exhibited a significant decrease in the establishment of latency in the spleen on day 16 postinfection, as measured by the frequency of viral genome-positive cells. In addition, M2 mutant viral genome

  11. [Macrophage colony stimulating factor enhances non-small cell lung cancer invasion and metastasis by promoting macrophage M2 polarization].

    Science.gov (United States)

    Li, Y J; Yang, L; Wang, L P; Zhang, Y

    2017-06-23

    Objective: To investigate the key cytokine which polarizes M2 macrophages and promotes invasion and metastasis in non-small cell lung cancer (NSCLC). Methods: After co-culture with A549 cells in vitro, the proportion of CD14(+) CD163(+) M2 macrophages in monocytes and macrophage colony stimulating factor (M-CSF) levels in culture supernatant were detected by flow cytometry, ELISA assay and real-time qPCR, respectively. The effects of CD14(+) CD163(+) M2 macrophages on invasion of A549 cells and angiogenesis of HUVEC cells were measured by transwell assay and tubule formation assay, respectively. The clinical and prognostic significance of M-CSF expression in NSCLC was further analyzed. Results: The percentage of CD14(+) CD163(+) M2 macrophages in monocytes and the concentration of M-CSF in the supernatant followed by co-culture was (12.03±0.46)% and (299.80±73.76)pg/ml, respectively, which were significantly higher than those in control group [(2.80±1.04)% and (43.07±11.22)pg/ml, respectively, P macrophages in vitro . M2 macrophages enhanced the invasion of A549 cells (66 cells/field vs. 26 cells/field) and the angiogenesis of HUVEC cells (22 tubes/field vs. 8 tubes/field). The mRNA expression of M-CSF in stage Ⅰ-Ⅱ patients (16.23±4.83) was significantly lower than that in stage Ⅲ-Ⅳ (53.84±16.08; P macrophages, which can further promote the metastasis and angiogenesis of NSCLC. M-CSF could be used as a potential therapeutic target of NSCLC.

  12. Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the alphaM2-cap.

    Directory of Open Access Journals (Sweden)

    Pallavi A Bafna

    2008-06-01

    Full Text Available Gating of nicotinic acetylcholine receptors from a C(losed to an O(pen conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where CO gating motions generate a lowhigh change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the alpha subunit ('alphaM2-cap'. This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. alphaM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three alphaM2-cap residues (alphaI260, alphaP265 and alphaS268 appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the alphaM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance.

  13. Exploring the MIS M2 glaciation occurring during a warm and high atmospheric CO2 Pliocene background climate

    Science.gov (United States)

    Tan, Ning; Ramstein, Gilles; Dumas, Christophe; Contoux, Camille; Ladant, Jean-Baptiste; Sepulchre, Pierre; Zhang, Zhongshi; De Schepper, Stijn

    2017-08-01

    Prior to the Northern Hemisphere glaciation around ∼2.7 Ma, a large global glaciation corresponding to a 20 to 60 m sea-level drop occurred during Marine Isotope Stage (MIS) M2 (3.312-3.264 Ma), interrupted the period of global warmth and high CO2 concentration (350-450 ppmv) of the mid Piacenzian. Unlike the late Quaternary glaciations, the M2 glaciation only lasted 50 kyrs and occurred under uncertain CO2 concentration (220-390 ppmv). The mechanisms causing the onset and termination of the M2 glaciation remain enigmatic, but a recent geological hypothesis suggests that the re-opening and closing of the shallow Central American Seaway (CAS) might have played a key role. In this article, thanks to a series of climate simulations carried out using a fully coupled Atmosphere Ocean General Circulation Model (GCM) and a dynamic ice sheet model, we show that re-opening of the shallow CAS helps precondition the low-latitude oceanic circulation and affects the related northward energy transport, but cannot alone explain the onset of the M2 glaciation. The presence of a shallow open CAS, together with favourable orbital parameters, 220 ppmv of CO2 concentration, and the related vegetation and ice sheet feedback, led to a global ice sheet build-up producing a global sea-level drop in the lowest range of proxy-derived estimates. More importantly, our results show that the simulated closure of the CAS has a negligible impact on the NH ice sheet melt and cannot explain the MIS M2 termination.

  14. Role of isoenzyme M2 of pyruvate kinase in urothelial tumorigenesis.

    Science.gov (United States)

    Zhou, Haiping; Wang, Xing; Mo, Lan; Liu, Yan; He, Feng; Zhang, Fenglin; Huang, Kuo-How; Wu, Xue-Ru

    2016-04-26

    The conversion of precancerous lesions to full-fledged cancers requires the affected cells to surpass certain rate-limiting steps. We recently showed that activation of HRAS proto-oncogene in urothelial cells of transgenic mice causes simple urothelial hyperplasia (SUH) which is persistent and whose transition to low-grade papillary urothelial carcinoma (UC) must undergo nodular urothelial hyperplasia (NUH). We hypothesized that NUH, which has acquired fibrovascular cores, plays critical roles in mesenchymal-to-epithelial signaling, breaching the barriers of urothelial tumor initiation. Using proteomics involving two-dimensional gel electrophoresis, immunoblotting with pan-phosphotyrosine antibody and MALDI-mass spectrometry, we identified isoform 2 of pyruvate kinase (PKM2) as the major tyrosine-phosphorylated protein switched on during NUH. We extended this finding using specimens from transgenic mice, human UC and UC cell lines, establishing that PKM2, but not its spliced variant PKM1, was over-expressed in low-grade and, more prominently, high-grade UC. In muscle-invasive UC, PKM2 was co-localized with cytokeratins 5 and 14, UC progenitor markers. Specific inhibition of PKM2 by siRNA or shRNA suppressed UC cell proliferation via increased apoptosis, autophagy and unfolded protein response. These results strongly suggest that PKM2 plays an important role in the genesis of low-grade non-invasive and high-grade invasive urothelial carcinomas.

  15. Estimation of genetic variability, mutagenic effectiveness and efficiency in M2 flower mutant lines of Capsicum annuum L. treated with caffeine and their analysis through RAPD

    Directory of Open Access Journals (Sweden)

    Rumana Aslam

    2017-07-01

    Full Text Available In the present investigation healthy and certified seeds of Capsicum annuum were treated with five concentrations of caffeine i.e. 0.10%, 0.25%, 0.50%, 0.75% and 1.0%. Germination percentage, plants survival and pollen fertility were decreased with the increase of caffeine concentrations. Similarly root length and shoot length were decreased as the concentrations increased in M1 generation. Different mutants were isolated in M1 generation. In M2 generation, various flower mutants with changes in number of sepals, petals, anther size colour i.e. Trimerous, tetramerous, pentamerous with fused petals, hexamerous etc were segregated. Heptamerous and anther change was not observed in lower concentration viz. 0.1%. All these mutants showed significant changes in morphological characters and good breeding values at lower and intermediate concentrations. Mutagenic effectiveness and efficiency was observed on the basis of M2 flower mutant frequency. It was generally decreased with the increase of mutagen concentrations. Cytological aberrations in mutants showed the decreasing trend at meiotic final stages. These mutants were further analysed through RAPD method and on the basis of appearance of polymorphic DNA bands, they distinguished these flower mutants genotypically. Among 93 bands 44 bands were polymorphic which showed great genetic variation produced by caffeine. As an outcome of that the above caffeine concentrations are good for the induction of genetic variability in Capsicum genotype.

  16. CD5L Promotes M2 Macrophage Polarization through Autophagy-Mediated Upregulation of ID3

    Directory of Open Access Journals (Sweden)

    Lucía Sanjurjo

    2018-03-01

    Full Text Available CD5L (CD5 molecule-like is a secreted glycoprotein that controls key mechanisms in inflammatory responses, with involvement in processes such as infection, atherosclerosis, and cancer. In macrophages, CD5L promotes an anti-inflammatory cytokine profile in response to TLR activation. In the present study, we questioned whether CD5L is able to influence human macrophage plasticity, and drive its polarization toward any specific phenotype. We compared CD5L-induced phenotypic and functional changes to those caused by IFN/LPS, IL4, and IL10 in human monocytes. Phenotypic markers were quantified by RT-qPCR and flow cytometry, and a mathematical algorithm was built for their analysis. Moreover, we compared ROS production, phagocytic capacity, and inflammatory responses to LPS. CD5L drove cells toward a polarization similar to that induced by IL10. Furthermore, IL10- and CD5L-treated macrophages showed increased LC3-II content and colocalization with acidic compartments, thereby pointing to the enhancement of autophagy-dependent processes. Accordingly, siRNA targeting ATG7 in THP1 cells blocked CD5L-induced CD163 and Mer tyrosine kinase mRNA and efferocytosis. In these cells, gene expression profiling and validation indicated the upregulation of the transcription factor ID3 by CD5L through ATG7. In agreement, ID3 silencing reversed polarization by CD5L. Our data point to a significant contribution of CD5L-mediated autophagy to the induction of ID3 and provide the first evidence that CD5L drives macrophage polarization.

  17. Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice.

    Science.gov (United States)

    Kang, Jung-Woo; Shin, Jun-Kyu; Koh, Eun-Ji; Ryu, Hyojeong; Kim, Hyoung Ja; Lee, Sun-Mee

    2016-04-01

    Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti-inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor α protein expression, it attenuated peroxisome proliferator-activated receptor γ expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor κB, tumor necrosis factor α, interleukin 6, TIR-domain-containing adapter-inducing interferon β, and interferon β levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

    1982-01-01

    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  19. Optimum design of a self-supported power transmission tower type 2M2 for 230 kW; Diseno optimo de una torre de transmision autosoportada tipo 2M2, para 230 kW

    Energy Technology Data Exchange (ETDEWEB)

    Espejel Valdez, Eduardo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico); Millan Monje, Alejandro; Honk Hernandez, Wenceslao [Comision Federal de Electricidad, (CFE), Mexico, D. F. (Mexico)

    1986-12-31

    A group of specialists from the Comision Federal de Electricidad (CFE) and of the Instituto de Investigaciones Electricas (IIE) analyzes the design of various types of power transmission towers in their application stage, in order to enhance them. In this article the structural characteristics of the self-supported tower type 2M2 for 230 kV of two circuits and of suspension, are presented. [Espanol] Un grupo de especialistas de la Comision Federal de Electricidad (CFE) y del Instituto de Investigaciones Electricas (IIE) analiza el diseno de diversos tipos de torres de transmision en su etapa de aplicacion, con el fin de mejorarlos. En este articulo se presentan las caracteristicas estructurales de la torre autosoportada tipo 2M2 para 230 kV, de dos circuitos y de suspension.

  20. Optimum design of a self-supported power transmission tower type 2M2 for 230 kW; Diseno optimo de una torre de transmision autosoportada tipo 2M2, para 230 kW

    Energy Technology Data Exchange (ETDEWEB)

    Espejel Valdez, Eduardo [Instituto de Investigaciones Electricas, Cuernavaca (Mexico); Millan Monje, Alejandro; Honk Hernandez, Wenceslao [Comision Federal de Electricidad, (CFE), Mexico, D. F. (Mexico)

    1985-12-31

    A group of specialists from the Comision Federal de Electricidad (CFE) and of the Instituto de Investigaciones Electricas (IIE) analyzes the design of various types of power transmission towers in their application stage, in order to enhance them. In this article the structural characteristics of the self-supported tower type 2M2 for 230 kV of two circuits and of suspension, are presented. [Espanol] Un grupo de especialistas de la Comision Federal de Electricidad (CFE) y del Instituto de Investigaciones Electricas (IIE) analiza el diseno de diversos tipos de torres de transmision en su etapa de aplicacion, con el fin de mejorarlos. En este articulo se presentan las caracteristicas estructurales de la torre autosoportada tipo 2M2 para 230 kV, de dos circuitos y de suspension.

  1. Characterization of Coal Quality Based On Ash Content From M2 Coal-Seam Group, Muara Enim Formation, South Sumatra Basin

    Directory of Open Access Journals (Sweden)

    Frillia Putri Nasution

    2017-09-01

    Full Text Available Muara Enim Formation is well known as coal-bearing formation in South Sumatra Basin. As coal-bearing formation, this formation was subjects of many integrated study. Muara Enim Formation can be divided into four coal-seam group, M1, M2, M3, and M4. The M2 group comprising of Petai (C, Suban (B, Lower Mangus (A2, and Upper Mangus (A1. Depositional environments of Group M2 is transitional lower delta plain with sub-depositional are crevasse splay and distributary channel. The differentiation of both sub-depositional environments can be caused the quality of coal deposit. One of quality aspects is ash content. This research conducted hopefully can give better understanding of relationship between depositional environments to ash content. Group M2 on research area were found only Seam C, Seam B, and Seam A2, that has distribution from north to central so long as 1400 m. Coal-seam thickness C ranged between 3.25-9.25 m, Seam B range 7.54-13.43 m, and Seam C range 1.53-8.37 m, where all of coal-seams thickening on the central part and thinning-splitting to northern part and southern part. The ash content is formed from burning coal residue material. Ash contents on coal seam caused by organic and inorganic compound which resulted from mixing modified material on surrounded when transportation, sedimentation, and coalification process. There are 27 sample, consists of 9 sample from Seam C, 8 sample from Seam B, and 10 sample from Seam A2. Space grid of sampling is 100-150 m. Ash content influenced by many factors, but in research area, main factor is existence of inorganic parting. Average ash content of Seam C is 6,04%, Seam B is 5,05%, and Seam A2 is 3,8%. Low ash content influenced by settle environment with minor detrital material. High ash content caused by oxidation and erosional process when coalification process. Ash content on coal in research area originated from detritus material carried by channel system into brackish area or originated

  2. 2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

    International Nuclear Information System (INIS)

    Ghosh, Ayanjeet; Gai, Feng; Hochstrasser, Robin M.; Wang, Jun; DeGrado, William F.; Moroz, Yurii S.; Korendovych, Ivan V.; Zanni, Martin

    2014-01-01

    Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs

  3. 2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Ayanjeet, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Gai, Feng, E-mail: ayanjeet@sas.upenn.edu, E-mail: gai@sas.upenn.edu; Hochstrasser, Robin M. [Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Wang, Jun; DeGrado, William F. [Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94143 (United States); Moroz, Yurii S.; Korendovych, Ivan V. [Department of Chemistry, Syracuse University, Syracuse, New York 13244 (United States); Zanni, Martin [Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706 (United States)

    2014-06-21

    Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs.

  4. M2 ocean tide parameters and the deceleration of the moon's mean longitude from satellite orbit data

    Science.gov (United States)

    Felsentreger, T. L.; Marsh, J. G.; Williamson, R. G.

    1979-01-01

    An estimation is made of the principal long-period spherical harmonic parameters in the representation of the M2 ocean tide from the orbital histories of the three satellites 1967-92A, Starlette, and GEOS 3. The data used are primarily the evolution of the orbital inclinations of the satellites in conjunction with the longitude of the ascending node from GEOS 3. Analysis procedure and analytic formulation, as well as ocean tidal parameter estimation and deceleration of the lunar mean longitude are outlined. The credibility of the M2 ocean tide solution is further enhanced by the close accord between the computed value for the deceleration of the lunar mean longitude and other recently reported estimates. It is evident from the results presented that studies of close earth satellite orbits are able to provide important information about the tidal forces acting on the earth.

  5. Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things

    Directory of Open Access Journals (Sweden)

    José L. Hernández-Ramos

    2015-07-01

    Full Text Available As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things.

  6. Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things

    Science.gov (United States)

    Hernández-Ramos, José L.; Bernabe, Jorge Bernal; Moreno, M. Victoria; Skarmeta, Antonio F.

    2015-01-01

    As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M) nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things. PMID:26140349

  7. A latency analysis for M2M and OG-like traffic patterns in different HSPA core network configurations

    Directory of Open Access Journals (Sweden)

    M. V. Popović

    2014-11-01

    Full Text Available In this paper we present an analysis intended to reveal possible impacts of core network features on latency for modelled M2M and Online Gaming traffic. Simulations were performed in a live 3G/HSPA network. Test traffic simulating multiplayer real-time games and M2M applications was generated on 10 mobile phones in parallel, sending data to a remote server. APNs with different combinations of hardware and features (proxy server, different GGSNs and firewalls, usage of Service Awareness feature were chosen. The traffic was recorded on the Gn interface in the mobile core. The goal of experiments was to evaluate any eventually significant variation of average recorded RTTs in the core part of mobile network that would clearly indicate either the impact of used APN on delay for a specific traffic pattern, or selectivity of the APN towards different traffic patterns.

  8. Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things.

    Science.gov (United States)

    Hernández-Ramos, José L; Bernabe, Jorge Bernal; Moreno, M Victoria; Skarmeta, Antonio F

    2015-07-01

    As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M) nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things.

  9. X-ray spectra, chemical bonding, and electron structure of ScM2Si2 (M = Fe, Co, Ni)

    International Nuclear Information System (INIS)

    Shcherba, I.D.; Kotur, B.Ya.

    1990-01-01

    In a study of the interaction of the components in the ternary systems Sc-M-Si (where M is a 3d transition metal) it was established that there are compounds of the empirical formula ScM 2 Si 2 (M = Fe, Co, Ni). They crystallize in two structural types, HfFe 2 Si 2 (the compound ScFe 2 Si 2 ) and CeGa 2 Al 2 (ScCo 2 Si 2 and ScNi 2 Si 2 ) (ref. 1), leading to different coordination environment of the atoms in the structures of the compounds. With the aim of investigating the electron structure and the type ofin these compounds, they authors made a systematic x-ray spectral investigation with simultaneous analysis of the crystal structures of ScM 2 Si 2

  10. Deletion of the M2-2 Gene from Avian Metapneumovirus Subgroup C (aMPV-C) Impairs Virus Replication and Immunogenicity in Turkeys

    Science.gov (United States)

    The second matrix (M2) gene of avian metapneumovirus subgroup C (aMPV-C) virus contains two overlapping open reading frames (ORFs), encoding two putative proteins, M2-1 and M2-2. Both proteins are believed to be involved in either viral RNA transcription or replication. To further characterize the f...

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

    Directory of Open Access Journals (Sweden)

    Arvind KUMAR

    2016-06-01

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

  12. Heterologous expression of Ralp3 in Streptococcus pyogenes M2 and M6 strains affects the virulence characteristics.

    Directory of Open Access Journals (Sweden)

    Nikolai Siemens

    Full Text Available BACKGROUND: Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS. In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii is Ralp3 actively lost during evolution in these serotypes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. CONCLUSIONS/SIGNIFICANCE: Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis.

  13. Heterologous expression of Ralp3 in Streptococcus pyogenes M2 and M6 strains affects the virulence characteristics.

    Science.gov (United States)

    Siemens, Nikolai; Kreikemeyer, Bernd

    2013-01-01

    Ralp3 is a transcriptional regulator present in a serotype specific fashion on the chromosome of the human pathogen Streptococcus pyogenes (group A streptococci, GAS). In serotypes harbouring the ralp3 gene either positive or negative effects on important metabolic and virulence genes involved in colonization and immune evasion in the human host were observed. A previous study revealed that deletion of ralp3 in a GAS M49 serotype significantly attenuated many virulence traits and caused metabolic disadvantages. This leads to two questions: (i) which kind of consequences could Ralp3 expression have in GAS serotypes naturally lacking this gene, and (ii) is Ralp3 actively lost during evolution in these serotypes. We investigated the role of Ralp3 in GAS M2 and M6 pathogenesis. Both serotypes lack ralp3 on their chromosome. The heterologous expression of ralp3 in both serotypes resulted in reduced attachment to and internalization into the majority of tested epithelial cells. Both ralp3 expression strains showed a decreased ability to survive in human blood and exclusively M2::ralp3 showed decreased survival in human serum. Both mutants secreted more active SpeB in the supernatant, resulting in a higher activity compared to wild type strains. The respective M2 and M6 wild type strains outcompeted the ralp3 expression strains in direct metabolic competition assays. The phenotypic changes observed in the M2:ralp3 and M6:ralp3 were verified on the transcriptional level. Consistent with the virulence data, tested genes showed transcript level changes in the same direction. Together these data suggest that Ralp3 can take over transcriptional control of virulence genes in serotypes lacking the ralp3 gene. Those serotypes most likely lost Ralp3 during evolution since obviously expression of this gene is disadvantageous for metabolism and pathogenesis.

  14. Electronic Structure and Bonding Situation in M2O2 (M=Be,Mg,Ca) Rhombic Clusters.

    Czech Academy of Sciences Publication Activity Database

    Li, W.-L.; Lu, J.-B.; Zhao, L.; Ponec, Robert; Cooper, D.L.; Li, J.; Frenking, G.

    Roč. 122, č. 10 ( 2018 ), s. 2816-2822 ISSN 1089-5639 Grant - others:NNSFCH(CN) 21590792; NNSFCH(CN) 21433005; NNSFCH(CN) 21703099; JPY NSF(CN) BK20170964; NTU(CN) 39837123 Institutional support: RVO:67985858 Keywords : electronic structures * M2O2n clustery * theoretical isnights Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 2.847, year: 2016

  15. On the simultaneous Pell equations x 2 - (4m 2 - 1)y 2 = y 2 - pz 2 ...

    African Journals Online (AJOL)

    Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 ...

  16. The strength of the M2 transition from the 7-/2 hole state in 43K

    International Nuclear Information System (INIS)

    Poletti, A.R.; Southon, J.R.

    1977-01-01

    The mean life of the 738 keV level of 43 K has been measured by direct electronic timing as tausub(m) = 265 +- 15 ns. The reaction 40 Ar(α,pγ) 43 K at 10.4 MeV was used to excite the level. A comparison is made with another recent measurement while the deduced M2 strength is compared with those in other potassium isotopes. (author)

  17. How well do we know the quantum numbers of possible anti p p → M1M2 states

    International Nuclear Information System (INIS)

    Lanou, R.E.

    1979-01-01

    Information is available to completely analyze the p anti p → ππ reaction, allowing more global, large-scale, phenomenological analyses which combine the two experimental data sets in an energy independent, amplitude analysis which also includes pion-nucleon data. It would appear from the preliminary analyses of p anti p → M 1 M 2 angular distributions and polarizations the T-region may indeed contain some very interesting activity

  18. Phosphorylation of the human respiratory syncytial virus P protein mediates M2-2 regulation of viral RNA synthesis, a process that involves two P proteins.

    Science.gov (United States)

    Asenjo, Ana; Villanueva, Nieves

    2016-01-04

    The M2-2 protein regulates the balance between human respiratory syncytial virus (HRSV) transcription and replication. Here it is shown that M2-2 mediated transcriptional inhibition is managed through P protein phosphorylation. Transcription inhibition by M2-2 of the HRSV based minigenome pRSVluc, required P protein phosphorylation at serines (S) in positions 116, 117, 119 and increased inhibition is observed if S232 or S237 is also phosphorylated. Phosphorylation of these residues is required for viral particle egression from infected cells. Viral RNA synthesis complementation assays between P protein variants, suggest that two types of P proteins participate in the process as components of RNA dependent RNA polymerase (RdRp). Type I is only functional when, as a homotetramer, it is bound to N and L proteins through residues 203-241. Type II is functionally independent of these interactions and binds to N protein at a region outside residues 232-241. P protein type I phosphorylation at S116, S117 and S119, did not affect the activity of RdRp but this phosphorylation in type II avoids its interaction with N protein and impairs RdRp functionality for transcription and replication. Structural changes in the RdRp, mediated by phosphorylation turnover at the indicated residues, in the two types of P proteins, may result in a fine adjustment, late in the infectious cycle, of transcription, replication and progression in the morphogenetic process that ends in egression of the viral particles from infected cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. He II Raman Scattered Line by Neutral Hydrogen in the Bipolar Platenary Nebula M2-9

    Directory of Open Access Journals (Sweden)

    Hee-Won Lee

    2001-06-01

    Full Text Available In the spectrum of the young bipolar planetary nebula M2-9 obtained from the 1.5 m telescope at the Cerro Tololo Inter-American Observatory, we detected the He~II feature at 6545 Å that are proposed to be formed via Raman scattering by atomic hydrogen. However, in the same spectrum, the He~II emission lines at 6527 Å and 6560 Å are absent, which implies that the He~II emission region is hidden from our line of sight and that the H~I scattering region is pretty much extended not to be obscured entirely. We performed photoionization computations to estimate the physical size of the He~II emission line region to be 1016 cm, from which the location and dimension of the obscuring circumstellar region are inferred and the temperature of the central star must exceed 105 K. The angular size of the circumstellar region responsible for the obscuration of the He~II emission region is ~ 1'' with the assumption of the distance 01 kpc to M2-9, which is consistent with the recent image of M2-9 obtained with the Hubble Space Telescope.

  20. Peculiarities of the intermediate valence state of Ce in CeM2Si2 (M = Fe, Co, Ni) compounds

    International Nuclear Information System (INIS)

    Koterlyn, M.; Shcherba, I.; Yasnitskii, R.; Koterlyn, G.

    2007-01-01

    The results of thermoelectric power and the electrical resistivity measurements connected with the intermediate valence (IV) of Ce are presented for the compounds CeM 2 Si 2 (M = Fe, Co, Ni) in the temperature range of 4-800 K. It is shown that CeM 2 Si 2 are Kondo-lattices with the coherence scale T coh ∼ 60-80 K and the so-called single-site Kondo temperature T K ∼ 10 3 K. On the example of CeNi 2 Si 2 we have studied the changes in the structure of density of f states (f-DOS) near the Fermi energy caused by atomic substitutions. The results of structural, transport, magnetic, and Ce L III X-ray absorption spectra measurements in the series Ce 1-x La x Ni 2 Si 2 (0 ≤ x ≤ 0.6), Ce(Ni 1-y Cu y ) 2 Si 2 (0 ≤ y ≤ 0.6) and CeNi 2 (Si 1-z Ge z ) 2 (0 ≤ z ≤ 0.5) are presented. We found that the IV state of Ce in the CeM 2 Si 2 is an evidence of possible opening a wide pseudogap Δ ∼ kT K within the f-DOS structure slightly above the Fermi energy

  1. Ultra-modular 500m2 heliostat field for high flux/high temperature solar-driven processes

    Science.gov (United States)

    Romero, Manuel; González-Aguilar, José; Luque, Salvador

    2017-06-01

    The main objective of the European Project SUN-to-LIQUID is the scale-up and experimental demonstration of the complete process chain to solar liquid fuels from H2O and CO2. This implies moving from a 4 kW laboratory setup to a pre-commercial plant including a heliostat field. The small power and high irradiance onto the focal spot is forcing the optical design to behave half way between a large solar furnace and an extremely small central receiver system. The customized heliostat field makes use of the most recent developments on small size heliostats and a tower with reduced optical height (15 m) to minimize visual impact. A heliostat field of 250kWth (500 m2 reflective surface) has been built adjacent to IMDEA Energy premises at the Technology Park of Móstoles, Spain, and consists of 169 small size heliostats (1.9 m × 1.6 m). In spite of the small size and compactness of the field, when all heliostats are aligned, it is possible to fulfil the specified flux above 2500 kW/m2 for at least 50 kW and an aperture of 16 cm, with a peak flux of 3000 kW/m2.

  2. The sodium fire tests performed in the FAUNA facility on up to 12m2 fire areas

    International Nuclear Information System (INIS)

    Cherdron, W.; Jordan, S.

    1983-08-01

    The FAUNA test facility started operation in 1979. It serves to investigate large area sodium fires in closed containments and to study the generation, behaviour and removal of sodium fire aerosols. In this report, the experimental results of the 6 sodium pool fires are described which were performed with up to 500 kg of sodium in fire pans of 2 m 2 , 5 m 2 and 12 m 2 surface area, respectively. Both, the thermodynamic data and the data of the reaction kinetics of the fires were determined. In addition, the behaviour of the released aerosols during and after the fire was studied. On the basis of measurements of the temperature profiles at various levels above the fire areas it was shown that the convective flows above fire areas of different sizes in closed containments differ markedly and, obviously, exert an influence on the development of the fire and the release of particles. Whilst in rather small fires the gas above the pan rises as in a chimney and flows back on the walls, no chimney effect can be observed in a large pool fire. In rather large fires higher burning rates and aerosol release rates were observed. Some meters above the fire area temperatures around 300-400 0 C, temporarily even up to 700 0 C, were measured. The tests F5 and F6 were performed above all to observe the fire behaviour in terms of thermodynamics and reaction kinetics in a fully closed containment. (orig./RW) [de

  3. Regional Spread of CTX-M-2-Producing Proteus mirabilis with the Identical Genetic Structure in Japan.

    Science.gov (United States)

    Kato, Karin; Matsumura, Yasufumi; Yamamoto, Masaki; Nagao, Miki; Takakura, Shunji; Ichiyama, Satoshi

    2017-07-01

    In this study, we analyzed the molecular epidemiology of extended-spectrum β-lactamase (ESBL)-producing Proteus mirabilis isolates collected from the central region of Japan. Between 2005 and 2012, 820 clinical P. mirabilis isolates were obtained from ten acute care hospitals in Japan. We characterized ESBL confirmatory test-positive isolates by sequencing the ESBL genes and their flanking regions, detecting plasmid replicons, and performing pulsed-field gel electrophoresis (PFGE). Ninety-six isolates (12%) were positive according to the ESBL confirmatory test; all these isolates possessed bla CTX-M-2 with the same flanking structure of upstream ΔISEcp1 and a downstream region identical to downstream bla KLUA-1 . IncT was the prevalent, and only, replicon found in 63 isolates. PFGE analysis detected eight clusters with more than one isolate, among which three included 56 isolates and six included isolates from multiple hospitals. CTX-M-2-producing P. mirabilis with an identical genetic structure flanking bla CTX-M-2 is dominant in this Japanese region, and there is evidence for the clonal spread of isolates.

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

    Directory of Open Access Journals (Sweden)

    Karina Sánchez-Reyes

    2014-01-01

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

  5. Zinc binding activity of human metapneumovirus M2-1 protein is indispensable for viral replication and pathogenesis in vivo.

    Science.gov (United States)

    Cai, Hui; Zhang, Yu; Ma, Yuanmei; Sun, Jing; Liang, Xueya; Li, Jianrong

    2015-06-01

    Human metapneumovirus (hMPV) is a member of the Pneumovirinae subfamily in the Paramyxoviridae family that causes respiratory tract infections in humans. Unlike members of the Paramyxovirinae subfamily, the polymerase complex of pneumoviruses requires an additional cofactor, the M2-1 protein, which functions as a transcriptional antitermination factor. The M2-1 protein was found to incorporate zinc ions, although the specific role(s) of the zinc binding activity in viral replication and pathogenesis remains unknown. In this study, we found that the third cysteine (C21) and the last histidine (H25) in the zinc binding motif (CCCH) of hMPV M2-1 were essential for zinc binding activity, whereas the first two cysteines (C7 and C15) play only minor or redundant roles in zinc binding. In addition, the zinc binding motif is essential for the oligomerization of M2-1. Subsequently, recombinant hMPVs (rhMPVs) carrying mutations in the zinc binding motif were recovered. Interestingly, rhMPV-C21S and -H25L mutants, which lacked zinc binding activity, had delayed replication in cell culture and were highly attenuated in cotton rats. In contrast, rhMPV-C7S and -C15S strains, which retained 60% of the zinc binding activity, replicated as efficiently as rhMPV in cotton rats. Importantly, rhMPVs that lacked zinc binding activity triggered high levels of neutralizing antibody and provided complete protection against challenge with rhMPV. Taken together, these results demonstrate that zinc binding activity is indispensable for viral replication and pathogenesis in vivo. These results also suggest that inhibition of zinc binding activity may serve as a novel approach to rationally attenuate hMPV and perhaps other pneumoviruses for vaccine purposes. The pneumoviruses include many important human and animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the leading causes of acute

  6. Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions.

    Science.gov (United States)

    Alvarado-Vazquez, Perla Abigail; Bernal, Laura; Paige, Candler A; Grosick, Rachel L; Moracho Vilrriales, Carolina; Ferreira, David Wilson; Ulecia-Morón, Cristina; Romero-Sandoval, E Alfonso

    2017-08-01

    M1 macrophages release proinflammatory factors during inflammation. They transit to an M2 phenotype and release anti-inflammatory factors to resolve inflammation. An imbalance in the transition from M1 to M2 phenotype in macrophages contributes to the development of persistent inflammation. CD163, a member of the scavenger receptor cysteine-rich family, is an M2 macrophage marker. The functional role of CD163 during the resolution of inflammation is not completely known. We postulate that CD163 contributes to the transition from M1 to M2 phenotype in macrophages. We induced CD163 gene in THP-1 and primary human macrophages using polyethylenimine nanoparticles grafted with a mannose ligand (Man-PEI). This nanoparticle specifically targets cells of monocytic origin via mannose receptors. Cells were challenged with a single or a double stimulation of lipopolysaccharide (LPS). A CD163 or empty plasmid was complexed with Man-PEI nanoparticles for cell transfections. Quantitative RT-PCR, immunocytochemistry, and ELISAs were used for molecular assessments. CD163-overexpressing macrophages displayed reduced levels of tumor necrosis factor-alpha (TNF)-α and monocytes chemoattractant protein (MCP)-1 after a single stimulation with LPS. Following a double stimulation paradigm, CD163-overexpressing macrophages showed an increase of interleukin (IL)-10 and IL-1ra and a reduction of MCP-1. This anti-inflammatory phenotype was partially blocked by an anti-CD163 antibody (effects on IL-10 and IL-1ra). A decrease in the release of TNF-α, IL-1β, and IL-6 was observed in CD163-overexpressing human primary macrophages. The release of IL-6 was blocked by an anti-CD163 antibody in the CD163-overexpressing group. Our data show that the induction of the CD163 gene in human macrophages under inflammatory conditions produces changes in cytokine secretion in favor of an anti-inflammatory phenotype. Targeting macrophages to induce CD163 using cell-directed nanotechnology is an attractive

  7. Protection against multiple influenza A virus strains induced by candidate recombinant vaccine based on heterologous M2e peptides linked to flagellin.

    Directory of Open Access Journals (Sweden)

    Liudmila A Stepanova

    Full Text Available Matrix 2 protein ectodomain (M2e is considered a promising candidate for a broadly protective influenza vaccine. M2e-based vaccines against human influenza A provide only partial protection against avian influenza viruses because of differences in the M2e sequences. In this work, we evaluated the possibility of obtaining equal protection and immune response by using recombinant protein on the basis of flagellin as a carrier of the M2e peptides of human and avian influenza A viruses. Recombinant protein was generated by the fusion of two tandem copies of consensus M2e sequence from human influenza A and two copies of M2e from avian A/H5N1 viruses to flagellin (Flg-2M2eh2M2ek. Intranasal immunisation of Balb/c mice with recombinant protein significantly elicited anti-M2e IgG in serum, IgG and sIgA in BAL. Antibodies induced by the fusion protein Flg-2M2eh2M2ek bound efficiently to synthetic peptides corresponding to the human consensus M2e sequence as well as to the M2e sequence of A/Chicken/Kurgan/05/05 RG (H5N1 and recognised native M2e epitopes exposed on the surface of the MDCK cells infected with A/PR/8/34 (H1N1 and A/Chicken/Kurgan/05/05 RG (H5N1 to an equal degree. Immunisation led to both anti-M2e IgG1 and IgG2a response with IgG1 prevalence. We observed a significant intracellular production of IL-4, but not IFN-γ, by CD4+ T-cells in spleen of mice following immunisation with Flg-2M2eh2M2ek. Immunisation with the Flg-2M2eh2M2ek fusion protein provided similar protection from lethal challenge with human influenza A viruses (H1N1, H3N2 and avian influenza virus (H5N1. Immunised mice experienced significantly less weight loss and decreased lung viral titres compared to control mice. The data obtained show the potential for the development of an M2e-flagellin candidate influenza vaccine with broad spectrum protection against influenza A viruses of various origins.

  8. The role of electrolyte anions (ClO4-, NO3-, and Cl-) in divalent metal (M2+) adsorption on oxide and hydroxide surfaces in salt solutions

    International Nuclear Information System (INIS)

    Criscenti, L.J.; Sverjensky, D.A.

    1999-01-01

    Adsorption of divalent metal ions (M 2+ ) onto oxide and hydroxide surfaces from solutions of strong electrolytes has typically been inferred to take place without the involvement of the electrolyte anion. Only in situations where M 2+ forms a strong enough aqueous complex with the electrolyte anion (for example, CdCl + or PbCl + ) has it been frequently suggested that the metal and the electrolyte anion adsorb simultaneously. A review of experimental data for the adsorption of Cd 2+ , Pb 2+ , Co 2+ , UO 2 2+ , Zn 2+ , Cu 2+ , Ba 2+ , Sr 2+ , and Ca 2+ onto quartz, silica, goethite, hydrous ferric oxide, corundum, γ-alumina, anatase, birnessite, and magnetite, from NaNO 3 , KNO 3 , NaCl, and NaClO 4 solutions over a wide range of ionic strengths (0.0001 M-1.0 M), reveals that transition and heavy metal adsorption behavior with ionic strength is a function of the type of electrolyte. In NaNO 3 solutions, metal adsorption exhibits little or no dependence on the ionic strength of the solution. However, in NaCl solutions, transition and heavy metal adsorption decreases strongly with increasing ionic strength. In NaClO 4 solutions, metal adsorption decreases strongly with increasing ionic strength. In NaClO 4 solutions, metal adsorption exhibits little dependence on ionic strength but is often suggestive of an increase in metal adsorption with increasing ionic strength. Analysis of selected adsorption edges was carried out using the extended triple-layer model and aqueous speciation models that included metal-nitrate, metal-chloride, and metal-hydroxide complexes

  9. Involvement of Proteasome and Macrophages M2 in the Protection Afforded by Telmisartan against the Acute Myocardial Infarction in Zucker Diabetic Fatty Rats with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    C. Di Filippo

    2014-01-01

    Full Text Available This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R. At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7% and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.

  10. Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes

    International Nuclear Information System (INIS)

    Kuo, W.-H.; Chou, F.-P.; Young, S.-C.; Chang, Y.-C.; Wang, C.-J.

    2005-01-01

    Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (∼1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators

  11. From WSN towards WoT: Open API Scheme Based on oneM2M Platforms

    Science.gov (United States)

    Kim, Jaeho; Choi, Sung-Chan; Ahn, Il-Yeup; Sung, Nak-Myoung; Yun, Jaeseok

    2016-01-01

    Conventional computing systems have been able to be integrated into daily objects and connected to each other due to advances in computing and network technologies, such as wireless sensor networks (WSNs), forming a global network infrastructure, called the Internet of Things (IoT). To support the interconnection and interoperability between heterogeneous IoT systems, the availability of standardized, open application programming interfaces (APIs) is one of the key features of common software platforms for IoT devices, gateways, and servers. In this paper, we present a standardized way of extending previously-existing WSNs towards IoT systems, building the world of the Web of Things (WoT). Based on the oneM2M software platforms developed in the previous project, we introduce a well-designed open API scheme and device-specific thing adaptation software (TAS) enabling WSN elements, such as a wireless sensor node, to be accessed in a standardized way on a global scale. Three pilot services are implemented (i.e., a WiFi-enabled smart flowerpot, voice-based control for ZigBee-connected home appliances, and WiFi-connected AR.Drone control) to demonstrate the practical usability of the open API scheme and TAS modules. Full details on the method of integrating WSN elements into three example systems are described at the programming code level, which is expected to help future researchers in integrating their WSN systems in IoT platforms, such as oneM2M. We hope that the flexibly-deployable, easily-reusable common open API scheme and TAS-based integration method working with the oneM2M platforms will help the conventional WSNs in diverse industries evolve into the emerging WoT solutions. PMID:27782058

  12. From WSN towards WoT: Open API Scheme Based on oneM2M Platforms

    Directory of Open Access Journals (Sweden)

    Jaeho Kim

    2016-10-01

    Full Text Available Conventional computing systems have been able to be integrated into daily objects and connected to each other due to advances in computing and network technologies, such as wireless sensor networks (WSNs, forming a global network infrastructure, called the Internet of Things (IoT. To support the interconnection and interoperability between heterogeneous IoT systems, the availability of standardized, open application programming interfaces (APIs is one of the key features of common software platforms for IoT devices, gateways, and servers. In this paper, we present a standardized way of extending previously-existing WSNs towards IoT systems, building the world of the Web of Things (WoT. Based on the oneM2M software platforms developed in the previous project, we introduce a well-designed open API scheme and device-specific thing adaptation software (TAS enabling WSN elements, such as a wireless sensor node, to be accessed in a standardized way on a global scale. Three pilot services are implemented (i.e., a WiFi-enabled smart flowerpot, voice-based control for ZigBee-connected home appliances, and WiFi-connected AR.Drone control to demonstrate the practical usability of the open API scheme and TAS modules. Full details on the method of integrating WSN elements into three example systems are described at the programming code level, which is expected to help future researchers in integrating their WSN systems in IoT platforms, such as oneM2M. We hope that the flexibly-deployable, easily-reusable common open API scheme and TAS-based integration method working with the oneM2M platforms will help the conventional WSNs in diverse industries evolve into the emerging WoT solutions.

  13. From WSN towards WoT: Open API Scheme Based on oneM2M Platforms.

    Science.gov (United States)

    Kim, Jaeho; Choi, Sung-Chan; Ahn, Il-Yeup; Sung, Nak-Myoung; Yun, Jaeseok

    2016-10-06

    Conventional computing systems have been able to be integrated into daily objects and connected to each other due to advances in computing and network technologies, such as wireless sensor networks (WSNs), forming a global network infrastructure, called the Internet of Things (IoT). To support the interconnection and interoperability between heterogeneous IoT systems, the availability of standardized, open application programming interfaces (APIs) is one of the key features of common software platforms for IoT devices, gateways, and servers. In this paper, we present a standardized way of extending previously-existing WSNs towards IoT systems, building the world of the Web of Things (WoT). Based on the oneM2M software platforms developed in the previous project, we introduce a well-designed open API scheme and device-specific thing adaptation software (TAS) enabling WSN elements, such as a wireless sensor node, to be accessed in a standardized way on a global scale. Three pilot services are implemented (i.e., a WiFi-enabled smart flowerpot, voice-based control for ZigBee-connected home appliances, and WiFi-connected AR.Drone control) to demonstrate the practical usability of the open API scheme and TAS modules. Full details on the method of integrating WSN elements into three example systems are described at the programming code level, which is expected to help future researchers in integrating their WSN systems in IoT platforms, such as oneM2M. We hope that the flexibly-deployable, easily-reusable common open API scheme and TAS-based integration method working with the oneM2M platforms will help the conventional WSNs in diverse industries evolve into the emerging WoT solutions.

  14. An analytical study of M2 tidal waves in the Taiwan Strait using an extended Taylor method

    Science.gov (United States)

    Wu, Di; Fang, Guohong; Cui, Xinmei; Teng, Fei

    2018-02-01

    The tides in the Taiwan Strait (TS) feature large semidiurnal lunar (M2) amplitudes. An extended Taylor method is employed in this study to provide an analytical model for the M2 tide in the TS. The strait is idealized as a rectangular basin with a uniform depth, and the Coriolis force and bottom friction are retained in the governing equations. The observed tides at the northern and southern openings are used as open boundary conditions. The obtained analytical solution, which consists of a stronger southward propagating Kelvin wave, a weaker northward propagating Kelvin wave, and two families of Poincaré modes trapped at the northern and southern openings, agrees well with the observations in the strait. The superposition of two Kelvin waves basically represents the observed tidal pattern, including an anti-nodal band in the central strait, and the cross-strait asymmetry (greater amplitudes in the west and smaller in the east) of the anti-nodal band. Inclusion of Poincaré modes further improves the model result in that the cross-strait asymmetry can be better reproduced. To explore the formation mechanism of the northward propagating wave in the TS, three experiments are carried out, including the deep basin south of the strait. The results show that the southward incident wave is reflected to form a northward wave by the abruptly deepened topography south of the strait, but the reflected wave is slightly weaker than the northward wave obtained from the above analytical solution, in which the southern open boundary condition is specified with observations. Inclusion of the forcing at the Luzon Strait strengthens the northward Kelvin wave in the TS, and the forcing is thus of some (but lesser) importance to the M2 tide in the TS.

  15. The influence of anharmonic vibrations of the core to M2-transition between low-lying states in 115Sn

    International Nuclear Information System (INIS)

    Sy Savane, Y.

    1995-12-01

    The influence of the anharmonicity of the core vibration, on the magnetic transition 11/2 - 1 → 7/2 + 1 in 115 Sn have been investigated in the frame of the quasiparticle-phonon nuclear model. The model wave function includes a ''quasiparticle + two phonons'' component. The performed numerical calculations show that those effects cannot explain the strong reduction of the M2-transition observed in the experiment. A full agreement with the experimental value is obtained with g eff s = 0.42g free s . (author). 10 refs, 2 figs, 1 tab

  16. Infinite number of solvable generalizations of XY-chain, with cluster state, and with central charge c = m/2

    Science.gov (United States)

    Minami, Kazuhiko

    2017-12-01

    An infinite number of spin chains are solved and it is derived that the ground-state phase transitions belong to the universality classes with central charge c = m / 2, where m is an integer. The models are diagonalized by automatically obtained transformations, many of which are different from the Jordan-Wigner transformation. The free energies, correlation functions, string order parameters, exponents, central charges, and the phase diagram are obtained. Most of the examples consist of the stabilizers of the cluster state. A unified structure of the one-dimensional XY and cluster-type spin chains is revealed, and other series of solvable models can be obtained through this formula.

  17. Spironolactone use and higher hospital readmission for Medicare beneficiaries with heart failure, left ventricular ejection fraction 73 m(2.).

    Science.gov (United States)

    Inampudi, Chakradhari; Parvataneni, Sridivya; Morgan, Charity J; Deedwania, Prakash; Fonarow, Gregg C; Sanders, Paul W; Prabhu, Sumanth D; Butler, Javed; Forman, Daniel E; Aronow, Wilbert S; Allman, Richard M; Ahmed, Ali

    2014-07-01

    Although randomized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction (HFrEF), they excluded patients with serum creatinine >2.5 mg/dl, and their use is contraindicated in those with advanced chronic kidney disease (CKD). In the present analysis, we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD. Of the 1,140 patients with HFrEF (EF 73 m(2)), 207 received discharge prescriptions for spironolactone. Using propensity scores (PSs) for the receipt of discharge prescriptions for spironolactone, we estimated PS-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for spironolactone-associated outcomes. Patients (mean age 76 years, 49% women, 25% African-American) had mean EF 28%, mean eGFR 31 ml/min/1.73 m(2), and mean potassium 4.5 mEq/L. Spironolactone use had significant PS-adjusted association with higher risk of 30-day (HR 1.41, 95% CI 1.04 to 1.90) and 1-year (HR 1.36, 95% CI 1.13 to 1.63) all-cause readmissions. The risk of 1-year all-cause readmission was higher among 106 patients with eGFR 73 m(2) (HR 4.75, 95% CI 1.84 to 12.28) than among those with eGFR 15 to 45 ml/min/1.73 m(2) (HR 1.34, 95% CI 1.11 to 1.61, p for interaction 0.003). Spironolactone use had no association with HF readmission and all-cause mortality. In conclusion, among hospitalized patients with HFrEF and advanced CKD, spironolactone use was associated with higher all-cause readmission but had no association with all-cause mortality or HF readmission. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Treatment in vitro with PPARα and PPARγ ligands drives M1-to-M2 polarization of macrophages from T. cruzi-infected mice.

    Science.gov (United States)

    Penas, Federico; Mirkin, Gerardo A; Vera, Marcela; Cevey, Ágata; González, Cintia D; Gómez, Marisa I; Sales, María Elena; Goren, Nora B

    2015-05-01

    Trypanosoma cruzi, the etiological agent of Chagas' disease, induces a persistent inflammatory response. Macrophages are a first line cell phenotype involved in the clearance of infection. Upon parasite uptake, these cells increase inflammatory mediators like NO, TNF-α, IL-1β and IL-6, leading to parasite killing. Although desired, inflammatory response perpetuation and exacerbation may lead to tissue damage. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent nuclear transcription factors that, besides regulating lipid and carbohydrate metabolism, have a significant anti-inflammatory effect. This is mediated through the interaction of the receptors with their ligands. PPARγ, one of the PPAR isoforms, has been implicated in macrophage polarization from M1, the classically activated phenotype, to M2, the alternatively activated phenotype, in different models of metabolic disorders and infection. In this study, we show for the first time that, besides PPARγ, PPARα is also involved in the in vitro polarization of macrophages isolated from T. cruzi-infected mice. Polarization was evidenced by a decrease in the expression of NOS2 and proinflammatory cytokines and the increase in M2 markers like Arginase I, Ym1, mannose receptor and TGF-β. Besides, macrophage phagocytic activity was significantly enhanced, leading to increased parasite load. We suggest that modulation of the inflammatory response by both PPARs might be due, at least in part, to a change in the profile of inflammatory macrophages. The potential use of PPAR agonists as modulators of overt inflammatory response during the course of Chagas' disease deserves further investigation. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Seed coat color, weight and eye pattern inheritance in gamma-rays induced cowpea M2-mutant line

    Directory of Open Access Journals (Sweden)

    Reda M. Gaafar

    2016-06-01

    Full Text Available Gamma radiation is a very effective tool for inducing genetic variation in characters of many plants. Black seeds of M2 mutant were obtained after exposure of an Egyptian cowpea cultivar (Kaha 1 to a low dose of gamma rays. Segregation of seed coat color, weight of 100 seeds and seed eye pattern of the black seeds of this mutant line were further examined in this study. Four colors were observed for seed coat in the M3 plants ranging from cream to reddish brown and three eye patterns were distinguished from each other. SDS–PAGE of the seed storage proteins showed 18 protein bands; five of these bands disappeared in the seeds of M3 plants compared to M2 and M0 controls while other 5 protein bands were specifically observed in seeds of M3 plants. PCR analysis using twelve ISSR primers showed 47 polymorphic and 8 unique amplicons. The eight unique amplicons were characteristic of the cream coat color and brown wide eye pattern (M03-G10 while the polymorphic bands were shared by 6 coat-color groups. A PCR fragment of 850 bp was amplified, using primer HB-12, in M3-G04 which showed high-100 seed weight. These results demonstrated the mutagenic effects of gamma rays on seed coat color, weight of 100 seeds and eye pattern of cowpea M3 mutant plants.

  20. A pH-dependent conformational ensemble mediates proton transport through the influenza A/M2 protein†

    Science.gov (United States)

    Polishchuk, Alexei L.; Lear, James D.; Ma, Chunlong; Lamb, Robert A.; Pinto, Lawrence H.; DeGrado, William F.

    2010-01-01

    The influenza A M2 protein exhibits inwardly rectifying, pH-activated proton transport that saturates at low pH. A comparison of high-resolution structures of the transmembrane domain at high and low pH suggests that pH-dependent conformational changes may facilitate proton conduction by alternately changing the accessibility of the N-terminal and C-terminal regions of the channel as a proton transits through the transmembrane domain. Here, we show that M2 functionally reconstituted in liposomes populates at least three different conformational states over a physiologically relevant pH range, with transition midpoints that are consistent with previously reported His37 pKas. We then develop and test two similar, quantitative mechanistic models of proton transport, where protonation shifts the equilibrium between structural states having different proton affinities and solvent accessibilities. The models account well for a collection of experimental data sets over a wide range of pHs and voltages and require only a small number of adjustable parameters to accurately describe the data. While the kinetic models do not require any specific conformation for the protein, they nevertheless are consistent with a large body of structural information based on high-resolution NMR and crystallographic structures, optical spectroscopy, and MD calculations. PMID:20968306

  1. Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization.

    Science.gov (United States)

    Chen, Xin; Ying, Xiang; Wang, Xinjing; Wu, Xiaoli; Zhu, Qinyi; Wang, Xipeng

    2017-07-01

    Hypoxia is a common feature of solid tumors. It is closely related to tumor progression. Exosomal microRNAs derived from cancers are considered to be mediators between cancer cells and the tumor microenvironment. In addition, the number of tumor-associated macrophages (TAMs) in the tumor microenvironment has also been demonstrated to correlate with tumor development. However, the relationship between tumor-secreted exosomes and TAM polarization under hypoxic conditions during tumor progression is not clear. Herein, we demonstrated that hypoxia induces the high expression of microRNA-940 (miR‑940) in exosomes derived from epithelial ovarian cancer (EOC). We also found that miR‑940 is highly expressed in exosomes isolated from ascites of EOC patients. Moreover, the overexpression of miR‑940 in macrophages delivered by exosomes stimulated M2 phenotype polarization, while the M2 subtype macrophages promoted EOC proliferation and migration. These results highlight the function of hypoxia in enhancing the high level of expression of miR‑940 in tumor exosomes taken up by macrophages. We also showed that the tumor-promoting function of miR‑940 is mediated by TAM polarization in EOC. These findings show that tumor-derived exosomal miR‑940 induced by hypoxia plays an important role in stimulating TAM polarization in the progression of EOC.

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

    Science.gov (United States)

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

    2012-07-01

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

  3. The development and testing of the thermal break divertor monoblock target design delivering 20 MW m-2 heat load capability

    Science.gov (United States)

    Fursdon, M.; Barrett, T.; Domptail, F.; Evans, Ll M.; Luzginova, N.; Greuner, N. H.; You, J.-H.; Li, M.; Richou, M.; Gallay, F.; Visca, E.

    2017-12-01

    The design and development of a novel plasma facing component (for fusion power plants) is described. The component uses the existing ‘monoblock’ construction which consists of a tungsten ‘block’ joined via a copper interlayer to a through CuCrZr cooling pipe. In the new concept the interlayer stiffness and conductivity properties are tuned so that stress in the principal structural element of the component (the cooling pipe) is reduced. Following initial trials with off-the-shelf materials, the concept was realized by machined features in an otherwise solid copper interlayer. The shape and distribution of the features were tuned by finite element analyses subject to ITER structural design criterion in-vessel components (SDC-IC) design rules. Proof of concept mock-ups were manufactured using a two stage brazing process verified by tomography and micrographic inspection. Full assemblies were inspected using ultrasound and thermographic (SATIR) test methods at ENEA and CEA respectively. High heat flux tests using IPP’s GLADIS facility showed that 200 cycles at 20 MW m-2 and five cycles at 25 MW m-2 could be sustained without apparent component damage. Further testing and component development is planned.

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

    Science.gov (United States)

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

    2017-08-21

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

  5. Adsorption of Reactive Red M-2BE dye from water solutions by multi-walled carbon nanotubes and activated carbon.

    Science.gov (United States)

    Machado, Fernando M; Bergmann, Carlos P; Fernandes, Thais H M; Lima, Eder C; Royer, Betina; Calvete, Tatiana; Fagan, Solange B

    2011-09-15

    Multi-walled carbon nanotubes and powdered activated carbon were used as adsorbents for the successful removal of Reactive Red M-2BE textile dye from aqueous solutions. The adsorbents were characterised by infrared spectroscopy, N(2) adsorption/desorption isotherms and scanning electron microscopy. The effects of pH, shaking time and temperature on adsorption capacity were studied. In the acidic pH region (pH 2.0), the adsorption of the dye was favourable using both adsorbents. The contact time to obtain equilibrium at 298K was fixed at 1h for both adsorbents. The activation energy of the adsorption process was evaluated from 298 to 323K for both adsorbents. The Avrami fractional-order kinetic model provided the best fit to the experimental data compared with pseudo-first-order or pseudo-second-order kinetic adsorption models. For Reactive Red M-2BE dye, the equilibrium data were best fitted to the Liu isotherm model. Simulated dyehouse effluents were used to check the applicability of the proposed adsorbents for effluent treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. M2 priority screening system for near-term activities: Project documentation. Final report December 11, 1992--May 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-08-12

    From May through August, 1993, the M-2 Group within M Division at LANL conducted with the support of the LANL Integration and Coordination Office (ICO) and Applied Decision Analysis, Inc. (ADA), whose purpose was to develop a system for setting priorities among activities. This phase of the project concentrated on prioritizing near-tenn activities (i.e., activities that must be conducted in the next six months) necessary for setting up this new group. Potential future project phases will concentrate on developing a tool for setting priorities and developing annual budgets for the group`s operations. The priority screening system designed to address the near-term problem was developed, applied in a series of meeting with the group managers, and used as an aid in the assignment of tasks to group members. The model was intended and used as a practical tool for documenting and explaining decisions about near-term priorities, and not as a substitute for M-2 management judgment and decision-making processes.

  7. Structure of vanadium oxosulfato complexes in V2O5-M2S2O7-M2SO4 (M = K, Cs) melts. A high temperature spectroscopic study

    DEFF Research Database (Denmark)

    Boghosian, S.; Chrissanthopoulos, A.; Fehrmann, Rasmus

    2002-01-01

    2 atmosphere (P-SO2 = 0-1.2 atm). The data are in agreement with the V-V V-IV equilibrium: (VO)(2)O(SO4)(4)(4-)(1) + SO2(g) 2VO(SO4)(2)(2-)(1) + SO3(g). SO2 does not coordinate to the V-V complex but starts significantly to coordinate to V-IV for P-SO2 > 0.4 atm according to VO(SO4)(2)(2-)(1) + SO2......(g) VO(SO4)(2)SO22-(1). The Raman spectral features and the exploitation of the relative Raman intensities indicate that the (VO)(2)O(SO4)(4)(4-) dimeric complex unit, possessing a V-O-V bridge, is formed in the V2O5-M2S2O7 binary mixtures. The spectral changes occurring upon interaction...

  8. Association between class III obesity (BMI of 40-59 kg/m2 and mortality: a pooled analysis of 20 prospective studies.

    Directory of Open Access Journals (Sweden)

    Cari M Kitahara

    2014-07-01

    Full Text Available The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2 has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2 compared with those classified as normal weight (BMI 18.5-24.9 kg/m2. Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009. Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively, followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively. Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3, 8

  9. Proto-planetary nebulae. I. The extreme bipolar nebulae M2-9 and M1-91

    International Nuclear Information System (INIS)

    Goodrich, R.W.

    1991-01-01

    Results are presented on a long-slit optical spectroscopy measurements of the prototype bipolar planetary nebula M2-9 and the M1-91 bipolar nebula, performed in order to determine the nature of the morphology of the wings of these two nebulae. It is concluded that the overall bipolar morphologies of these nebulae might be due to the orbital motions of binaries, with the orbital angular momentum vector defining the axis of the nebula. Secondary symmetries in the nebulae, such as the point-symmetric knots in M1-91, could be due to other symmetries, such as the rotation axis of one of the individual stars or the polar axis of the accretion disk. 39 refs

  10. Equilibrium water vapor pressures over polyvanadates M2V12O30.7·nH2O

    International Nuclear Information System (INIS)

    Volkov, V.L.; Zakharova, G.S.; Ivakin, A.A.

    1986-01-01

    Equilibrium pressures of water vapors over polyvanadates M 2 V 12 O 30.7 xnH 2 O where M=Li, Na, K are determined in the 293-343 K temperature range. Changes in Gibbs free energy and enthalpy of compound dehydration depending on water content in the final product are calculated on the basis of these data. Molar enthalpy of water is shown to reduce from lithium to potassium, while equilibrium pressure of water vapors over the compounds grows from lithium to potassium. Good correlation of thermodynamic properties of crystallization water of polyvanadates with energy characteristics of hydrated M + ions of the solutions confirms the conclusion that they cannot be attributed to ordinary crystallohydrates

  11. Magnetic characteristics of M2FeV3O11 (M = Mg, Zn, Pb, Co, Ni) compounds

    Science.gov (United States)

    Groń, T.; Blonska-Tabero, A.; Filipek, E.; Stokłosa, Z.; Duda, H.; Sawicki, B.

    2018-02-01

    The unusual physical characteristics of the multicomponent oxide systems renewed the interest as the potential cathode materials in high-energy cells. Since the earlier magnetic characteristics were not entirely conclusive, we report the results of dc magnetic measurements including higher harmonics of ac magnetic susceptibility of the M2FeV3O11 (M = Mg, Zn, Pb, Co, Ni) compounds. Ferrimagnetic long-range and antiferromagnetic short-range interactions for all compounds under study at low temperatures as well as superparamagnetic-like behavior with the blocking temperature of 29 K and the freezing parameter of 0.013 were observed. These effects are discussed within the framework of superexchange and double exchange magnetic interactions as well as the mixed valence band of iron ions.

  12. Assessment Report Sandia National Laboratories Fuel Cycle Technologies Quality Assurance Evaluation of FY15 SNL FCT M2 Milestone Deliverables

    Energy Technology Data Exchange (ETDEWEB)

    Appel, Gordon John [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-05-01

    Sandia National Laboratories (SNL) Fuel Cycle Technologies (FCT) program activities are conducted in accordance with FCT Quality Assurance Program Document (FCT-QAPD) requirements. The FCT-QAPD interfaces with SNL approved Quality Assurance Program Description (SNL-QAPD) as explained in the Sandia National Laboratories QA Program Interface Document for FCT Activities (Interface Document). This plan describes SNL's FY16 assessment of SNL's FY15 FCT M2 milestone deliverable's compliance with program QA requirements, including SNL R&A requirements. The assessment is intended to confirm that SNL's FY15 milestone deliverables contain the appropriate authenticated review documentation and that there is a copy marked with SNL R&A numbers.

  13. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal Tokomak with circular cross sections

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1976-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the Tokomak with circular cross sections. One includes the resistive and diamagnetic effects in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, one obtains a system of two coupled equations for the harmonic amplitudes. When the shear is finite on q=1, the toroidal coupling is negligible. In the opposite limit, one can explain: the experimental behaviour of the (m=1, n=1) mode before the internal disruption; the simultaneous observation of the modes (m=1, n=1) and [de

  14. Assessment Report Sandia National Laboratories Fuel Cycle Technologies Quality Assurance Evaluation of FY15 SNL FCT M2 Milestone Deliverables

    International Nuclear Information System (INIS)

    Appel, Gordon John

    2016-01-01

    Sandia National Laboratories (SNL) Fuel Cycle Technologies (FCT) program activities are conducted in accordance with FCT Quality Assurance Program Document (FCT-QAPD) requirements. The FCT-QAPD interfaces with SNL approved Quality Assurance Program Description (SNL-QAPD) as explained in the Sandia National Laboratories QA Program Interface Document for FCT Activities (Interface Document). This plan describes SNL's FY16 assessment of SNL's FY15 FCT M2 milestone deliverable's compliance with program QA requirements, including SNL R&A requirements. The assessment is intended to confirm that SNL's FY15 milestone deliverables contain the appropriate authenticated review documentation and that there is a copy marked with SNL R&A numbers.

  15. Infinite number of solvable generalizations of XY-chain, with cluster state, and with central charge c=m/2

    Directory of Open Access Journals (Sweden)

    Kazuhiko Minami

    2017-12-01

    Full Text Available An infinite number of spin chains are solved and it is derived that the ground-state phase transitions belong to the universality classes with central charge c=m/2, where m is an integer. The models are diagonalized by automatically obtained transformations, many of which are different from the Jordan–Wigner transformation. The free energies, correlation functions, string order parameters, exponents, central charges, and the phase diagram are obtained. Most of the examples consist of the stabilizers of the cluster state. A unified structure of the one-dimensional XY and cluster-type spin chains is revealed, and other series of solvable models can be obtained through this formula.

  16. Multipole induced splitting of metal-cage vibrations in crystalline endohedral D2d-M2@C84 dimetallofullerenes.

    Science.gov (United States)

    Krause, M; Popov, V N; Inakuma, M; Tagmatarchis, N; Shinohara, H; Georgi, P; Dunsch, L; Kuzmany, H

    2004-01-22

    Metal-carbon cage vibrations of crystalline endohedral D2d-M2@C84 (M=Sc,Y,Dy) dimetallofullerenes were analyzed by temperature dependent Raman scattering and a dynamical force field model. Three groups of metal-carbon cage modes were found at energies of 35-200 cm(-1) and assigned to metal-cage stretching and deformation vibrations. They exhibit a textbook example for the splitting of molecular vibrations in a crystal field. Induced dipole-dipole and quadrupole-quadrupole interactions account quantitatively for the observed mode splitting. Based on the metal-cage vibrational structure it is demonstrated that D2d-Y2@C84 dimetallofullerene retains a monoclinic crystal structure up to 550 K and undergoes a transition from a disordered to an ordered orientational state at a temperature of approximately 150 K.

  17. Ultra-Compact 100 × 100 μm2 Footprint Hybrid Device with Spin-Valve Nanosensors

    Directory of Open Access Journals (Sweden)

    Diana C. Leitao

    2015-12-01

    Full Text Available Magnetic field mapping with micrometric spatial resolution and high sensitivity is a challenging application, and the technological solutions are usually based on large area devices integrating discrete magnetic flux guide elements. In this work we demonstrate a high performance hybrid device with improved field sensitivity levels and small footprint, consisting of a ultra-compact 2D design where nanometric spin valve sensors are inserted within the gap of thin-film magnetic flux concentrators. Pole-sensor distances down to 400 nm are demonstrated using nanofabrication techniques combined with an optimized liftoff process. These 100 × 100 μm 2 pixel sensors can be integrated in modular devices for surface mapping without moving parts.

  18. Growth kinetics of boride coatings formed at the surface AISI M2 during dehydrated paste pack boriding

    Energy Technology Data Exchange (ETDEWEB)

    Doñu Ruiz, M.A., E-mail: mdonur0800@alumno.ipn.mx [Universidad Politécnica del Valle de México UPVM, Grupo Ciencia e Ingeniería de Materiales, Av. Mexiquense S/N Esquina Av. Universidad Politécnica, Col Villa Esmeralda, 54910 Tultitlan (Mexico); López Perrusquia, N.; Sánchez Huerta, D. [Universidad Politécnica del Valle de México UPVM, Grupo Ciencia e Ingeniería de Materiales, Av. Mexiquense S/N Esquina Av. Universidad Politécnica, Col Villa Esmeralda, 54910 Tultitlan (Mexico); Torres San Miguel, C.R.; Urriolagoitia Calderón, G.M. [Instituto Politécnico Nacional, SEPI-ESIME, Unidad Profesional Adolfo López Mateos Zacatenco, Edificio 5, 2do. Piso, Col. Lindavista, CP 07738 México, D.F. (Mexico); Cerillo Moreno, E.A. [Universidad Politécnica del Valle de México UPVM, Grupo Ciencia e Ingeniería de Materiales, Av. Mexiquense S/N Esquina Av. Universidad Politécnica, Col Villa Esmeralda, 54910 Tultitlan (Mexico); Cortes Suarez, J.V. [Univerisdad Autónoma Metropolitana Unidad Azcapotzalco, Av. San Pablo 180 Azcapotzalco 02200, Área de Ciencia de los Materiales, México, D.F. (Mexico)

    2015-12-01

    The growth kinetics of the boride coatings (FeB and Fe{sub 2}B) at the surface of AISI M2 high speed steels were studied in this work. Boriding thermochemical treatment was carried out by dehydrated paste pack at three different temperatures 1173, 1223, and 1273 K and four exposure times 1, 3, 5, and 7 h, respectively. The presence of FeB and Fe{sub 2}B phases was identified by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction method. In order to obtain the boron diffusion coefficients at the FeB/Fe{sub 2}B boride coatings, a mathematical model based on the mass balance at the growing interfaces was proposed under certain assumptions. Likewise the parabolic growth constants and the boride incubation time were established as a function of the parameters η (T) and ε (T). The activation energy values estimated for the FeB and Fe{sub 2}B layers were 233.42 and 211.89 kJ mol{sup −1} respectively. A good agreement was obtained between the simulated values of boride layer thicknesses and the experimental results. Finally, empirical relationships of boride coating thickness as a function of boriding temperature and time are presented. - Highlights: • Formed boride coatings at the surface of AISI M2 high speed steels by new process dehydrated paste pack boriding. • The model was based on the mass balance equation at the FeB/Fe{sub 2}B and Fe{sub 2}B/Fe interfaces by considering the boride incubation time. • A good agreement was obtained between the simulated values of boride layers coatings and the experimental results.

  19. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Mi Eun Kim

    2017-11-01

    Full Text Available The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS-induced nitric oxide (NO production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  20. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

    Science.gov (United States)

    Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

    2017-11-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  1. Cardioprotective Action of Ginkgo biloba Extract against Sustained β-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway

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    Thássio R. R. Mesquita

    2017-05-01

    Full Text Available Ginkgo biloba is the most popular phytotherapic agent used worldwide for treatment of several human disorders. However, the mechanisms involved in the protective actions of Ginkgo biloba on cardiovascular diseases remain poorly elucidated. Taking into account recent studies showing beneficial actions of cholinergic signaling in the heart and the cholinergic hypothesis of Ginkgo biloba-mediated neuroprotection, we aimed to investigate whether Ginkgo biloba extract (GBE promotes cardioprotection via activation of cholinergic signaling in a model of isoproterenol-induced cardiac hypertrophy. Here, we show that GBE treatment (100 mg/kg/day for 8 days, v.o. reestablished the autonomic imbalance and baroreflex dysfunction caused by chronic β-adrenergic receptor stimulation (β-AR, 4.5 mg/kg/day for 8 days, i.p.. Moreover, GBE prevented the upregulation of muscarinic receptors (M2 and downregulation of β1-AR in isoproterenol treated-hearts. Additionally, we demonstrated that GBE prevents the impaired endothelial nitric oxide synthase activity in the heart. GBE also prevented the pathological cardiac remodeling, electrocardiographic changes and impaired left ventricular contractility that are typical of cardiac hypertrophy. To further investigate the mechanisms involved in GBE cardioprotection in vivo, we performed in vitro studies. By using neonatal cardiomyocyte culture we demonstrated that the antihypertrophic action of GBE was fully abolished by muscarinic receptor antagonist or NOS inhibition. Altogether, our data support the notion that antihypertrophic effect of GBE occurs via activation of M2/NO pathway uncovering a new mechanism involved in the cardioprotective action of Ginkgo biloba.

  2. Photoelectron Spectroscopy and Density Functional Theory Studies of Iron Sulfur (FeS)m- (m = 2-8) Cluster Anions: Coexisting Multiple Spin States.

    Science.gov (United States)

    Yin, Shi; Bernstein, Elliot R

    2017-10-05

    Iron sulfur cluster anions (FeS) m - (m = 2-8) are studied by photoelectron spectroscopy (PES) at 3.492 eV (355 nm) and 4.661 eV (266 nm) photon energies, and by density functional theory (DFT) calculations. The most probable structures and ground state spin multiplicities for (FeS) m - (m = 2-8) clusters are tentatively assigned through a comparison of their theoretical and experiment first vertical detachment energy (VDE) values. Many spin states lie within 0.5 eV of the ground spin state for the larger (FeS) m - (m ≥ 4) clusters. Theoretical VDEs of these low lying spin states are in good agreement with the experimental VDE values. Therefore, multiple spin states of each of these iron sulfur cluster anions probably coexist under the current experimental conditions. Such available multiple spin states must be considered when evaluating the properties and behavior of these iron sulfur clusters in real chemical and biological systems. The experimental first VDEs of (FeS) m - (m = 1-8) clusters are observed to change with the cluster size (number m). The first VDE trends noted can be related to the different properties of the highest singly occupied molecular orbitals (NBO, HSOMOs) of each cluster anion. The changing nature of the NBO/HSOMO of these (FeS) m - (m = 1-8) clusters from a p orbital on S, to a d orbital on Fe, and to an Fe-Fe bonding orbital is probably responsible for the observed increasing trend for their first VDEs with respect to m.

  3. The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

    International Nuclear Information System (INIS)

    Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

    2014-01-01

    Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma

  4. Machining tools in AISI M2 high-speed steel obtained by spray forming process; Ferramentas de usinagem em aco rapido AISI M2 obtido por conformacao por 'spray'

    Energy Technology Data Exchange (ETDEWEB)

    Jesus, Edilson Rosa Barbosa de. E-mail: erbjesus@usp.br

    2004-07-01

    The aim of the present work was the obtention of AISI M2 high-speed steel by spray forming technique and the material evaluation when used as machining tool. The obtained material was hot rolled at 50% and 72% reduction ratios, and from which it was manufactured inserts for machining tests. The performance of inserts made of the spray formed material was compared to inserts obtained from conventional and powder metallurgy (MP) processed materials. The spray formed material was chemical, physical, mechanical and microstructural characterised. For further characterisation, the materials were submitted to machining tests for performance evaluation under real work condition. The results of material characterisation highlight the potential of the spray forming technique, in the obtention of materials with good characteristics and properties. Under the current processing, hot rolling and heat treatments condition, the analysis of the results of the machining tests revealed a very similar behaviour among the tested materials. Proceeding a criterious analysis of the machining results tests, it was verified that the performance presented by the powder metallurgy material (MP) was slight superior, followed by conventional obtained material (MConv), which presented a insignificant advantage over the spray formed and hot rolled (72% reduction ratio) material. The worst result was encountered for the spray forming and hot rolled (50% reduction ratio) material that presented the highest wear values. (author)

  5. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.

    Directory of Open Access Journals (Sweden)

    Lorena Itatí Ibañez

    Full Text Available The ectodomain of influenza A matrix protein 2 (M2e is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs. We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+ T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2 or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.

  6. M2Lite: An Open-source, Light-weight, Pluggable and Fast Proteome Discoverer MSF to mzIdentML Tool.

    Science.gov (United States)

    Aiyetan, Paul; Zhang, Bai; Chen, Lily; Zhang, Zhen; Zhang, Hui

    2014-04-28

    Proteome Discoverer is one of many tools used for protein database search and peptide to spectrum assignment in mass spectrometry-based proteomics. However, the inadequacy of conversion tools makes it challenging to compare and integrate its results to those of other analytical tools. Here we present M2Lite, an open-source, light-weight, easily pluggable and fast conversion tool. M2Lite converts proteome discoverer derived MSF files to the proteomics community defined standard - the mzIdentML file format. M2Lite's source code is available as open-source at https://bitbucket.org/paiyetan/m2lite/src and its compiled binaries and documentation can be freely downloaded at https://bitbucket.org/paiyetan/m2lite/downloads.

  7. Maternal obesity is the new challenge; a qualitative study of health professionals’ views towards suitable care for pregnant women with a Body Mass Index (BMI ≥30 kg/m2

    Directory of Open Access Journals (Sweden)

    Smith Debbie M

    2012-12-01

    Full Text Available Abstract Background An increase in the number of women with maternal obesity (Body Mass Index [BMI] ≥30 kg/m2 has had a huge impact on the delivery of maternity services. As part of a programme of feasibility work to design an antenatal lifestyle programme for women with a BMI ≥30 kg/m2, the current study explored health professionals’ experiences of caring for women with a BMI ≥30 kg/m2 and their views of the proposed lifestyle programme. Method Semi-structured interviews with 30 health professionals (including midwives, sonographers, anaesthetists and obstetricians were conducted and analysed using thematic analysis. Recruitment occurred in two areas in the North West of England in early 2011. Results Three themes were evident. Firstly, obesity was seen as a conversation stopper; obesity can be a challenge to discuss. Secondly, obesity was seen as a maternity issue; obesity has a direct impact on maternity care and therefore intervention is needed. Finally, the long-term impact of maternal obesity intervention; lifestyle advice in pregnancy has the potential to break the cyclic obesity relationship. The health professionals believed that antenatal lifestyle advice can play a key role in addressing the public health issue of obesity as pregnancy is a time of increased motivation for women with a BMI ≥30 kg/m2. Conclusions Maternal obesity is a challenge and details of the training content required for health professionals to feel confident to approach the issue of maternal obesity with women are presented. Support for the antenatal lifestyle programme for women with a BMI ≥30 kg/m2 highlights the need for further exploration of the impact of interventions on health promotion.

  8. Multi-wave band SMM-VLA observations of an M2 flare and an associated coronal mass ejection

    Science.gov (United States)

    Willson, Robert F.; Lang, Kenneth R.; Schmelz, Joan T.; Gonzalez, Raymond D.; Smith, Kermit L.

    1991-01-01

    Results are presented of observations of an M2 flare and an associated coronal mass ejection CME by instruments on the SMM as well as by the VLA and other ground-based observatories on September 30, 1988. The multiwave band data show a gradual slowly changing event which lasted several hours. The microwave burst emission was found to originate in compact moderately circularly polarized sources located near the sites of bright H-alpha and soft X-ray emission. These data are combined with estimates of an electron temperature of 1.5 x 10 to the 7th K and an emission measure of about 2.0 x 10 to the 49th/cu cm obtained from Ca XIX and Fe XXV spectra to show that the microwave emission can be attributed to thermal gyrosynchrotron radiation in regions where the magnetic field strength is 425-650 G. The CME acceleration at low altitudes is measured on the basis of ground- and space-based coronagraphs.

  9. Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer.

    Science.gov (United States)

    Chao, Tai-Kuang; Huang, Tien-Shuo; Liao, Yu-Ping; Huang, Rui-Lan; Su, Po-Hsuan; Shen, Hueng-Yuan; Lai, Hung-Cheng; Wang, Yu-Chi

    2017-01-01

    Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor progression-free survival rates (p = 0.01) as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70-5.85). In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001). We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05) and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.

  10. Sleep During Pregnancy: The nuMoM2b Pregnancy and Sleep Duration and Continuity Study.

    Science.gov (United States)

    Reid, Kathryn J; Facco, Francesca L; Grobman, William A; Parker, Corette B; Herbas, Marcos; Hunter, Shannon; Silver, Robert M; Basner, Robert C; Saade, George R; Pien, Grace W; Manchanda, Shalini; Louis, Judette M; Nhan-Chang, Chia-Lang; Chung, Judith H; Wing, Deborah A; Simhan, Hyagriv N; Haas, David M; Iams, Jay; Parry, Samuel; Zee, Phyllis C

    2017-05-01

    To characterize sleep duration, timing and continuity measures in pregnancy and their association with key demographic variables. Multisite prospective cohort study. Women enrolled in the nuMoM2b study (nulliparous women with a singleton gestation) were recruited at the second study visit (16-21 weeks of gestation) to participate in the Sleep Duration and Continuity substudy. Women sleep log for 7 consecutive days. Time in bed, sleep duration, fragmentation index, sleep efficiency, wake after sleep onset, and sleep midpoint were averaged across valid primary sleep periods for each participant. Valid data were available from 782 women with mean age of 27.3 (5.5) years. Median sleep duration was 7.4 hours. Approximately 27.9% of women had a sleep duration of sleep duration of >9 hours. In multivariable models including age, race/ethnicity, body mass index, insurance status, and recent smoking history, sleep duration was significantly associated with race/ethnicity and insurance status, while time in bed was only associated with insurance status. Sleep continuity measures and sleep midpoint were significantly associated with all covariates in the model, with the exception of age for fragmentation index and smoking for wake after sleep onset. Our results demonstrate the relationship between sleep and important demographic characteristics during pregnancy. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  11. Spectroscopic Observation of Water-Mediated Deformation of the CARBOXYLATE-M2+ (M= Mg, Ca) Contact Ion Pair

    Science.gov (United States)

    Kelleher, Patrick J.; DePalma, Joseph W.; Johnson, Mark

    2016-06-01

    The binding of alkaline earth dications to the biologically relevant carboxylate ligand has previously been studied using vibrational sum frequency generation (VSFG) spectroscopy of the air-water interface, infrared multiple photon dissociation (IRMPD) spectroscopy of clusters, and DFT methods. These results suggest the presence of both monodentate and bidentate binding motifs of the M2+ ions to the cayboxyl head groups depending on the extent of solvation. We revisit these systems using vibrational predissociation spectroscopy to measure the gas-phase vibrational spectra of the D2-tagged microhydrated [MgOAc(H2O)n=1-5]+ and [CaOAc(H2O)n=1-6]+ clusters. The spectra show that [MgOAc(H2O)n]+ switches from bidentate to monodentate binding promptly at n = 5, while [CaOAc(H2O)n]+ retains its bidentate attachment such that the sixth water molecule initiates the second solvation shell. The difference in binding behavior between these two divalent metal ions is analyzed in the context of the local acidity of the solvent water molecules and the strength of the metal-carboxylate and metal-water interactions. This cluster study provides insight into the chemical physics underlying the unique and surprising impacts of Mg2+ and Ca2+ on the chemistry mediated by sea spray aerosols. Funding for this work was provided by the NSF's Center for Aerosol Impacts on Climate and the Environment.

  12. Reproducibility of flap thickness with IntraLase FS and Moria LSK-1 and M2 microkeratomes.

    Science.gov (United States)

    Talamo, Jonathan H; Meltzer, Jeremy; Gardner, John

    2006-06-01

    To compare flap thickness reproducibility of the femtosecond laser and two mechanical microkeratomes. Flap thickness for all eyes was measured as the difference between the preoperative (day of surgery) full corneal thickness and post-flap creation central stromal bed thickness using ultrasonic pachymetry. Flap thickness values produced by three different microkeratome systems were compared for accuracy and reproducibility. For 99 flaps created using the IntraLase FS laser with an intended thickness of 110 microm, the mean achieved thickness was 119 +/- 12 microm (range: 82 to 149 microm). In 100 eyes treated with the Moria LSK-1 microkeratome with an intended flap thickness of 160 microm, the mean achieved thickness was 130 +/- 19 microm (range: 71 to 186 microm). In 135 eyes treated with the Moria M2 microkeratome with an intended flap thickness of 130 microm, mean thickness was 142 +/- 24 microm (range: 84 to 203 microm). The standard deviation and range of corneal flap thickness created with the IntraLase FS laser was significantly smaller than either mechanical microkeratome (P < .0001). When compared to two commonly used mechanical microkeratomes, mean achieved flap thickness was more reproducible with the IntraLase FS laser, reducing the comparative risk of overly thick flaps.

  13. Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Tai-Kuang Chao

    Full Text Available Pyruvate kinase M2 (PKM2 regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001 and pathogenesis models (p < 0.001, had poor progression-free survival rates (p = 0.01 as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70-5.85. In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001. We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05 and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.

  14. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies.

    Science.gov (United States)

    Wu, Jiayuan; Hu, Liren; Chen, Manyu; Cao, Wenjun; Chen, Haicong; He, Taiping

    2016-01-01

    The expression of pyruvate kinase M2 (PKM2) has been linked to tumor formation and invasion. Specifically, the relationship between high PKM2 expression and prognosis has been evaluated in solid tumors of digestive system. However, the prognostic value of PKM2 remains controversial. A literature search of PubMed, Embase, and Cochrane databases was conducted until October 2015. The end point focused on overall survival (OS). The pooled hazard ratio (HR) or odds ratio and the 95% confidence intervals were calculated to correlate PKM2 overexpression with OS and clinicopathological characteristics by employing fixed- or random-effects models, depending on the heterogeneity of the included studies. We identified 18 cohorts in 16 studies involving 2,812 patients for this meta-analysis. Overall, the combined HR for OS in all tumor types was 1.74 (1.44-2.11; Pdigestive system, thereby suggesting that PKM2 might be an indicator of poor prognosis in digestive system cancers.

  15. In silico screening, genotyping, molecular dynamics simulation and activity studies of SNPs in pyruvate kinase M2.

    Directory of Open Access Journals (Sweden)

    Ponnusamy Kalaiarasan

    Full Text Available Role of, 29-non-synonymous, 15-intronic, 3-close to UTR, single nucleotide polymorphisms (SNPs and 2 mutations of Human Pyruvate Kinase (PK M2 were investigated by in-silico and in-vitro functional studies. Prediction of deleterious substitutions based on sequence homology and structure based servers, SIFT, PANTHER, SNPs&GO, PhD-SNP, SNAP and PolyPhen, depicted that 19% emerged common between all the mentioned programs. SNPeffect and HOPE showed three substitutions (C31F, Q310P and S437Y in-silico as deleterious and functionally important. In-vitro activity assays showed C31F and S437Y variants of PKM2 with reduced activity, while Q310P variant was catalytically inactive. The allosteric activation due to binding of fructose 1-6 bisphosphate (FBP was compromised in case of S437Y nsSNP variant protein. This was corroborated through molecular dynamics (MD simulation study, which was also carried out in other two variant proteins. The 5 intronic SNPs of PKM2, associated with sporadic breast cancer in a case-control study, when subjected to different computational analyses, indicated that 3 SNPs (rs2856929, rs8192381 and rs8192431 could generate an alternative transcript by influencing splicing factor binding to PKM2. We propose that these, potentially functional and important variations, both within exons and introns, could have a bearing on cancer metabolism, since PKM2 has been implicated in cancer in the recent past.

  16. The monoclinic superstructure of the M2Pt6Al15 series (M=Ca, Sc, Y, La, Lu)

    International Nuclear Information System (INIS)

    Radzieowski, Mathis; Stegemann, Frank; Hoffmann, Rolf-Dieter; Janka, Oliver; Oldenburg Univ.

    2017-01-01

    The five ternary intermetallic compounds M 2 Pt 6 Al 15 (M=Ca, Sc, Y, La, Lu) were prepared from the elements by arc-melting. The crystal structure was determined via single crystal X-ray diffraction. The title compounds crystallize in a superstructure of the RE 0.67 Pt 2 Al 5 type structure (P6 3 /mmc) in the monoclinic crystal system with space group P12 1 /m1 (Sc 2 Pt 6 Al 15 : a=734.19(2), b=1628.96(10), c=734.19(2) pm, β=119.999(3) ; wR=0.0356, 3034 F 2 values, 68 variables). The superstructure can be derived by the superspace formalism using (3+2)D or (3+1)D interpretations of the diffraction data. The structural relation to the subcell structure is discussed on the basis of a group-subgroup scheme. In the crystal structure strongly bonded [Pt 2 Al 4 ] δ- slabs are alternatingly stacked with ordered layers containing M atoms and Al 3 triangles.

  17. Comparative Study Between the Effect of Myofascial Release Using M2T Blade and Kinesiotape on Recreational Badminton Shoulder Pain Subjects: A Randomised Clinical Trial

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    Varun Naik

    2017-05-01

    Full Text Available Background: Shoulder pain is one of the most common conditions seen in recreational badminton players. It is caused due to repeated movements at the shoulder joint which further limits the range of motion and hence hampers the activities of daily living. M2T helps to release the myofascial tightness which causes the pain. Kinesiotape also helps in increasing the range of motion. Patients and Methods: Thirty recreational shoulder pain subjects were assessed and treated between the age group of 18-30 years at the KLE University’s Indoor Stadium, Jawaharlal Nehru Medical College, Belagavi, Karnataka, India. Methods: The recreational shoulder pain subjects were divided into Group “A” and Group “B” by Randomized clinical trial. Outcome measures used were the visual analogue scale (VAS for pain and the Disability of Arm, Hand, and Shoulder (DASH. VAS and DASH were assessed pre-treatment and post-treatment. Results: Inter-group comparison for both the groups had differences but showed no statistical significance. Hence based on results it can be concluded that both the treatment techniques are effective in reducing pain and increasing ability at the shoulder joint.

  18. Decommissioning of NPP A-1

    International Nuclear Information System (INIS)

    Anon

    2009-01-01

    In this presentation the Operation history of A1 NPP, Project 'Decommissioning of A1 NPP' - I stage, Project 'Decommissioning of A1 NPP ' - II stage and Next stages of Project 'Decommissioning of A1 NPP ' are discussed.

  19. An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses

    Directory of Open Access Journals (Sweden)

    Chan Chris CS

    2010-01-01

    Full Text Available Abstract Background A growing concern has raised regarding the pandemic potential of the highly pathogenic avian influenza (HPAI H5N1 viruses. Consequently, there is an urgent need to develop an effective and safe vaccine against the divergent H5N1 influenza viruses. In the present study, we designed a tetra-branched multiple antigenic peptide (MAP-based vaccine, designated M2e-MAP, which contains the sequence overlapping the highly conserved extracellular domain of matrix protein 2 (M2e of a HPAI H5N1 virus, and investigated its immune responses and cross-protection against different clades of H5N1 viruses. Results Our results showed that M2e-MAP vaccine induced strong M2e-specific IgG antibody responses following 3-dose immunization of mice with M2e-MAP in the presence of Freunds' or aluminium (alum adjuvant. M2e-MAP vaccination limited viral replication and attenuated histopathological damage in the challenged mouse lungs. The M2e-MAP-based vaccine protected immunized mice against both clade1: VN/1194 and clade2.3.4: SZ/406H H5N1 virus challenge, being able to counteract weight lost and elevate survival rate following lethal challenge of H5N1 viruses. Conclusions These results suggest that M2e-MAP presenting M2e of H5N1 virus has a great potential to be developed into an effective subunit vaccine for the prevention of infection by a broad spectrum of HPAI H5N1 viruses.

  20. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression

    DEFF Research Database (Denmark)

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