369 research outputs found

    Simultaneous OH-PLIF and schlieren imaging of flame acceleration in an obstacle-laden channel

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    Flame acceleration in stoichiometric H_2/O_2 at 12 and 25 kPa initial pressure in an obstacle-laden square cross-section channel was studied experimentally using planar laser-induced fluorescence imaging of hydroxyl radicals (OH-PLIF) and simultaneous high-speed schlieren imaging. Results were obtained resolving the explosion front structure as it develops immediately after ignition as a slow-flame to the eventual formation of a shock-flame complex in the fast-flame regime. The images provide a novel level of detail and allow for the determination of the effects of turbulence-flame and shock-flame interaction. In the slow-flame regime, vortex shedding off obstacle edges occurs over long time-scales, vortices are convected downstream and turbulent combustion takes place in the obstacle wakes. The fast-flame regime is marked by the presence of compression waves (and shock waves) which interact with the flame and cause macroscopic deformation of the flame and small-scale wrinkling due to Richtmyer-Meshkov instability. A quasi-steady fast-flame is characterized by the close proximity of the precursor shock and the turbulent flame. The flow-field that governs the flame shape is established impulsively by the precursor shock. Shock-flame interactions lead to flame front perturbations on both small and large scales. The OH-PLIF technique makes it possible to discern the flame front from other density interfaces that appear in the complex fast-flame structure observed in schlieren images and also eliminates the line-of-sight integration limitation

    Newtonian and Post-Newtonian approximations of the k = 0 Friedmann Robertson Walker Cosmology

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    In a previous paper we derived a post-Newtonian approximation to cosmology which, in contrast to former Newtonian and post-Newtonian cosmological theories, has a well-posed initial value problem. In this paper, this new post-Newtonian theory is compared with the fully general relativistic theory, in the context of the k = 0 Friedmann Robertson Walker cosmologies. It is found that the post-Newtonian theory reproduces the results of its general relativistic counterpart, whilst the Newtonian theory does not.Comment: 11 pages, Latex, corrected typo

    Simultaneous OH-PLIF and schlieren imaging of flame acceleration in an obstacle-laden channel

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    Flame acceleration in stoichiometric H_2/O_2 at 12 and 25 kPa initial pressure in an obstacle-laden square cross-section channel was studied experimentally using planar laser-induced fluorescence imaging of hydroxyl radicals (OH-PLIF) and simultaneous high-speed schlieren imaging. Results were obtained resolving the explosion front structure as it develops immediately after ignition as a slow-flame to the eventual formation of a shock-flame complex in the fast-flame regime. The images provide a novel level of detail and allow for the determination of the effects of turbulence-flame and shock-flame interaction. In the slow-flame regime, vortex shedding off obstacle edges occurs over long time-scales, vortices are convected downstream and turbulent combustion takes place in the obstacle wakes. The fast-flame regime is marked by the presence of compression waves (and shock waves) which interact with the flame and cause macroscopic deformation of the flame and small-scale wrinkling due to Richtmyer-Meshkov instability. A quasi-steady fast-flame is characterized by the close proximity of the precursor shock and the turbulent flame. The flow-field that governs the flame shape is established impulsively by the precursor shock. Shock-flame interactions lead to flame front perturbations on both small and large scales. The OH-PLIF technique makes it possible to discern the flame front from other density interfaces that appear in the complex fast-flame structure observed in schlieren images and also eliminates the line-of-sight integration limitation

    Post-Newtonian Cosmology

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    Newtonian Cosmology is commonly used in astrophysical problems, because of its obvious simplicity when compared with general relativity. However it has inherent difficulties, the most obvious of which is the non-existence of a well-posed initial value problem. In this paper we investigate how far these problems are met by using the post-Newtonian approximation in cosmology.Comment: 12 pages, Late

    Rationale and evidence for the incorporation of heparin to the diclofenac epolamine medicated plaster

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    The nonsteroidal anti-inflammatory drug (NSAID) diclofenac epolamine (DHEP) formulated as a topical patch has demonstrated efficacy and safety in the localized treatment of acute pain from minor strains, sprains, and contusions, and for epicondylitis and knee osteoarthritis. The glycosaminoglycan heparin enhances the activity of topical NSAIDs formulated as a medicated plaster, even in the absence of any significant release of heparin. Therefore, DHEP Plus, a new formulation of the DHEP medicated plaster containing a small amount of heparin sodium as excipient has been developed. Methods: We reviewed the pivotal and supportive studies of the clinical development program of the new patch and evaluated the role of heparin as an enhancer in the treatment of localized pain/inflammation of musculoskeletal structures, associated with post-traumatic and/or rheumatic conditions. Results: The data were consistent with the concept that heparin increased the clinical activity of the DHEP Plus medicated plaster versus the reference DHEP medicated plaster through improved bioavailability due to enhanced movement of diclofenac from the plaster. Both DHEP formulations have the same dissolution profile, indicating that heparin does not change the physical and chemical characteristics of the plaster. Permeation testing showed that heparin is not released from the DHEP Plus medicated plaster. Efficacy studies showed that the DHEP Plus medicated plaster was significantly more effective in reducing pain than the reference marketed DHEP medicated plaster. Conclusions: The benefit/risk assessment of DHEP Plus 180 mg medicated plaster is favorable, with a safety profile equal to placebo and improved efficacy over the reference marketed DHEP medicated plaster

    Ketorolak-dekstran konjugati: sinteza, in vitro i in vivo vrednovanje

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    Ketorolac is a non-steroidal anti-inflammatory drug. Dextran conjugates of ketorolac (KD) were synthesized and characterized to improve ketorolac aqueous solubility and reduce gastrointestinal side effects. An N-acylimidazole derivative of ketorolac (KAI) was condensed with a model carrier polymer, dextran of different molecular masses (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding. Ketorolac contents were evaluated by UV-spectrophotometric analysis. The molecular mass was determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis studies were performed in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (V/V) human plasma (pH 7.4). At pH 9, a higher rate of ketorolac release from KD was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo biological screening in mice and rats indicated that conjugates retained analgesic and anti-inflammatory activities with significantly reduced ulcerogenicity compared to the parent drug.U radu je opisana sinteza konjugata dektrana i protuupalnog lijeka ketorolaka (KD). Konjugati su pripravljeni da bi se povećala topljivost ketorolaka u vodi i smanjila njegova nusdjelovanja u gastrointestinanom traktu. Ketorak je prvo preveden u N-acilimidazolni derivat (KAI) koji je kondenziran s polimernim nosačem, dekstranom različitih molekulskih masa (40000, 60000, 110000 i 200000). IR-spektri potvrdili su nastajanje esterske veze. Udio ketorolaka u konjugatu određen je UV-spektrofotometrijskom analizom. Molekulske mase određene su mjerenjem viskoznosti koristeći Mark-Howink-Sakurada jednadžbu. Hidroliza in vitro praćena je u puferskim otopinama (pH 1,2, 7,4 i 9) i u 80% V/V humanoj plazmi (pH 7,4). Pri pH 9 primjećeno je značajno brže oslobađanje ketorolaka iz KD nego u puferskoj otopini pH 7,4 i krvnoj plazmi. Oslobađanje je prati kinetiku prvog reda. In vivo biološka ispitivanja na miševima i štakorima ukazuju da konjugati imaju analgetsko i protuupalno djelovanje, a značajno smanjeno ulcerogeno djelovanje

    Identification and characterization of a novel non-structural protein of bluetongue virus

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    Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

    Mechanism of action of novel NO-releasing furoxan derivatives of aspirin in human platelets

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    1. Incorporation of a nitric oxide (NO)-releasing moiety in aspirin can overcome its gastric side effects. 2. We investigated the NO-release patterns and antiplatelet effects of novel furoxan derivatives of aspirin (B8 and B7) in comparison to existing antiplatelet agents. 3. Cyclooxygenase (COX) activity was investigated in purified enzyme using an electron paramagnetic resonance-based technique. Concentration–response curves for antiplatelet agents±the soluble guanylate cyclase inhibitor, ODQ (50 μM) were generated in platelet-rich plasma (PRP) and washed platelets (WP) activated with collagen using turbidometric aggregometry. NO was detected using an isolated NO electrode. 4. The furoxan derivatives of aspirin (B8, B7) and their NO-free furazan equivalents (B16, B15; all 100 μM) significantly inhibited COX activity (P<0.01; n=6) in vitro and caused aspirin-independent, cGMP-dependent inhibition of collagen-induced platelet aggregation in WP. B8 was more potent than B7 (PRP IC(50)=0.62±0.1 μM for B8; 400±89 μM for B7; P<0.0001. WP IC(50)s=0.6±0.1 and 62±10 μM, respectively). The NO-free furazan counterparts were less potent antiplatelet agents (WP IC(50)s=54±3 μM and 62±10 μM, respectively; P<0.0001, B8 vs B16). Of the hybrids investigated, only B8 retained antiplatelet activity in PRP. 5. NO release from furoxan–aspirin hybrids was undetectable in buffer alone, but was accelerated in the presence of either plasma or plasma components, albumin (4%), glutathione (GSH; 3 μM) and ascorbate (50 μM), the effects of which were additive for B7 but not B8. NO generation from furoxans was greatly enhanced by platelet extract, an effect that could largely be explained by the synergistic effect of intracellular concentrations of GSH (3 mM) and ascorbate (1 mM). 6. We conclude that the decomposition of furoxan–aspirin hybrids to generate biologically active NO is catalysed by endogenous agents which may instil a potential for primarily intracellular delivery of NO. The blunting of the aspirin effects of furoxan hybrids is likely to be due to loss of the acetyl moiety in plasma; the observed antiplatelet effects are thereby primarily mediated via NO release. Compounds of this class might represent a novel means of inhibiting platelet aggregation by a combination of NO generation and COX inhibition

    Dental calculus and isotopes provide direct evidence of fish and plant consumption in Mesolithic Mediterranean

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    In this contribution we dismantle the perceived role of marine resources and plant foods in the subsistence economy of Holocene foragers of the Central Mediterranean using a combination of dental calculus and stable isotope analyses. The discovery of fish scales and flesh fragments, starch granules and other plant and animal micro-debris in the dental calculus of a Mesolithic forager dated to the end of the 8th millenium BC and buried in the Vlakno Cave on Dugi Otok Island in the Croatian Archipelago demonstrates that marine resources were regularly consumed by the individual together with a variety of plant foods. Since previous stable isotope data in the Eastern Adriatic and the Mediterranean region emphasises that terrestrial-based resources contributed mainly to Mesolithic diets in the Mediterranean Basin, our results provide an alternative view of the dietary habits of Mesolithic foragers in the Mediterranean region based on a combination of novel methodologies and data
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