1,784 research outputs found

    2,9-Dimethyl-7-phenyl-N-(4-methyl­phen­yl)dibenzo[b,h][1,6]naphthyridin-6-amine

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    The title compound, C31H25N3, was synthesized from 6,4′,4′′-trimethyl-2,4-bis­(N-phenyl­amino)­quinoline and is the first structural example containing a phenyl and phenyl­amino fragment attached to a fused dibenzo[1,6]naphthyridine moiety. The fused tetra­cyclic ring system is essentially planar [r.m.s. deviation = 0.08 (3) Å]. The phenyl ring and the phenyl­amino group are inclined by 82.68 (6) and 35.31 (5)°, respectively, to the mean plane of the fused tetra­cyclic ring system. A weak intra­molecular N—H⋯π(arene) inter­action may in part influence the conformation of the mol­ecule. In the crystal, mol­ecules are linked by weak inter­molecular C—H⋯N hydrogen bonds into centrosymmetric dimers. Additional stabilization is provided by weak C—H⋯π and π–π stacking inter­actions [centroid–centroid distances = 3.834 (2) and 3.898 (1) Å]

    Does the 1/f frequency-scaling of brain signals reflect self-organized critical states?

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    Many complex systems display self-organized critical states characterized by 1/f frequency scaling of power spectra. Global variables such as the electroencephalogram, scale as 1/f, which could be the sign of self-organized critical states in neuronal activity. By analyzing simultaneous recordings of global and neuronal activities, we confirm the 1/f scaling of global variables for selected frequency bands, but show that neuronal activity is not consistent with critical states. We propose a model of 1/f scaling which does not rely on critical states, and which is testable experimentally.Comment: 3 figures, 6 page

    7-(2-Chloro­phen­yl)-2,6,9-trimethyl­dibenzo[b,h][1,6]naphthyridine

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    In the title compound, C25H19ClN2, the dibenzo[b,h][1,6]naphthyridine system is planar to within 0.16 (2) Å, and the chloro­phenyl ring is inclined to it by 82.53 (7)°. In the crystal, mol­ecules are linked by C—H⋯N hydrogen bonds, forming chains propagating in [100]. There are also a number of weak π–π stacking inter­actions present [centroid–centroid distances = 3.8531 (1) and 3.7631 (1) Å]

    Perceptions of the Impact of Positive Action in EU and non-EU Countries

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    yesAbstract: Around the world, inequalities exist around boundaries of race, social class, gender, disability, religious beliefs and sexual orientation, often resulting from past and current discriminatory practices. Governments have taken certain measures, including enacting policies such as positive action, to remedy such discrimination. This paper provides a comparative analysis of perceptions of the impact of positive action in seven EU and three non-EU countries. The study adopted participatory methods including consensus workshops, interviews and policy analysis to obtain data from designers of positive action. Findings are discussed, conclusions drawn and wide-ranging recommendations are made at the EC, individual countries and organisational levels

    Methodological Challenges of Researching Positive Action Measures

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    This paper highlights some ofthe methodological challenges which have arisen in collecting data for an international study on positive action measures. It will describe strategies employed to encourage participation in the study from as wide a range of organisations and individuals using a mixed method approach. The paper will also discuss the methodological and sensitive issues related to this type of research in organisations and strategies adopted by the research team to ameliorate any problems that have arisen whilst maintaining trustworthiness and rigour in the study

    Positive Action Measures Across Different Equality Grounds, Organisations and Sectors in European and Non-european Countries

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    yesAbstract: This article is based on a large-scale European Commission project on international perspectives on positive action measures. The paper presents an analysis of the perceptions of positive action held by respondents from all the countries participating in an international survey, focussing specifically upon differences across equality grounds, sector and organisation type. This paper will also provide examples of positive action being applied in European and non-European countries that participated in the study. The study adopted extensive literate and online survey to obtain data from designers of positive action. Findings are discussed, conclusions drawn and wide-ranging recommendations are made at the European Commission, individual countries and organisational levels

    Decreased venous thrombosis with an oral inhibitor of P selectin

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    BackgroundP-selectin inhibition with protein therapeutics such as antibodies or soluble ligands given intravenously can decrease thrombosis in a mouse ligation model of venous thrombosis. In this study, we hypothesized that oral inhibition of P selectin with a novel oral nonprotein inhibitor (PSI-697) would decrease thrombosis and circulating microparticle populations. This study evaluated the effects on thrombosis and circulating microparticle populations in this murine venous thrombosis model.MethodsMice underwent inferior vena cava ligation to induce thrombosis. Mice with high circulating level of P selectin, Delta Cytoplasmic Tail (^CT), mice gene-deleted for both E- and P-selectin knockout (EPKO), and wild-type C57BL/6 mice (WT) were studied without and with administration of PSI-697 in food (100 mg/kg daily) from 2 days before thrombosis until the end of the study. Animals were killed 2 and 6 days later. Evaluations included thrombus weight (TW), vein wall morphometrics, microparticle quantification by using fluorescence-activated cell sorter analysis, and vein wall enzyme-linked immunosorbent assays for interleukin (IL)-10, P selectin, and monocyte chemotactic protein 1.ResultsPSI-697 significantly decreased TW in WT and ^CT mice, with a treated vs nontreated TW of 132 ± 24 vs 228 ± 29 × 10−4 g (P = .014) and 166 ± 19 vs 281 ± 16 × 10−4 g (P = .001), respectively. At day 6, the effect was significant only in the ^CT group (P < .05). Drug therapy at day 2 significantly increased vein wall monocytes in WT mice and increased monocytes and total inflammatory cells in ^CT animals. A significant decrease in neutrophils and total inflammatory cells was seen in EPKO mice at day 2 with therapy. Therapy significantly increased platelet-derived microparticles and total microparticles in ^CT mice on day 2. Changes in treated WT and treated EPKO animals were not significant compared with respective vehicle treatments at day 2. On day 6, therapy significantly decreased total microparticles in EPKO animals. Vein wall expression of IL-10 increased in all groups with therapy at day 2 (n = 18) and was significantly increased in WT (2687.5 ± 903 pg/mL vs 636 ± 108 pg/mL total protein; P = .038) and ^CT (2078 ± 295 pg/mL vs 432 ± 62 pg/mL total protein; P = .001) mice. Therapy significantly decreased vein wall P selectin, monocyte chemotactic protein 1, and IL-10 levels at day 6.ConclusionsPSI-697 decreased thrombosis. P-selectin inhibition allowed vein wall inflammatory cell extravasation in this model of complete ligation. Circulating microparticles (platelet-derived microparticles and total microparticles) increased with P-selectin inhibition, possibly because of decreased consumption into the thrombus. In summary, the oral administration of an inhibitor to P selectin provides significant TW reduction.Clinical RelevanceDeep venous thrombosis is a significant national health problem in the general population. The average annual incidence of deep venous thrombosis is approximately 250,000 cases per year. The selectin family of adhesion molecules is thought to be largely responsible for the initial attachment and rolling of leukocytes on stimulated vascular endothelium. Recent studies have explored the possible therapeutic implications of P-selectin inhibition to modulate venous thrombosis. For example, prophylactic dosing of a recombinant P-selectin ligand decreases venous thrombosis in a dose-dependent fashion in both feline and nonhuman primate animal models. Additionally, treatment of 2-day iliac thrombi with a recombinant protein, P-selectin inhibitor, significantly improves vein reopening in nonhuman primates. It is interesting to note that P-selectin inhibition decreases thrombosis without adverse anticoagulation. On the basis of the results from these previous studies, the use of P-selectin antagonism is a logical therapeutic approach to treat venous thrombosis. All inhibitors developed to date are either proteins or small molecules with low oral bioavailability that require intravenous or subcutaneous injection. This study evaluates, for the first time, a novel orally bioavailable inhibitor of P-selectin (PSI-697)
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