Tiltrotor CFD part II: aerodynamic optimisation of tiltrotor blades

This paper presents aerodynamic optimisation of tiltrotor blades with high-fidelity computational fluid dynamics. The employed optimisation framework is based on a quasi-Newton method, and the required high-fidelity flow gradients were computed using a discrete adjoint solver. Single-point optimisations were first performed, to highlight the contrasting requirements of the helicopter and aeroplane flight regimes. It is then shown how a trade-off blade design can be obtained using a multi-point optimisation strategy. The parametrisation of the blade shape allowed to modify the twist and chord distributions, and to introduce a swept tip. The work shows how these main blade shape parameters influence the optimal performance of the tiltrotor in helicopter and aeroplane modes, and how a compromise blade shape can increase the overall tiltrotor performance. Moreover, in all the presented cases, the accuracy of the adjoint gradients resulted in a small number of flow evaluations for finding the optimal solution, thus indicating gradient-based optimisation as a viable tool for modern tiltrotor design

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

New filamentary remnant radio emission and duty cycle constraints in the radio galaxy NGC 6086

Radio galaxies are a subclass of active galactic nuclei in which accretion onto the supermassive black hole releases energy via relativistic jets. The jets are not constantly active throughout the life of the host galaxy and alternate between active and quiescent phases. Remnant radio galaxies are detected during a quiescent phase and define a class of unique sources to constrain the AGN duty cycle. We present, a spatially resolved radio analysis of the radio galaxy associated with NGC 6086 and constraints on the spectral age of the diffuse emission to investigate the duty cycle and evolution of the source. We use three new low-frequency, high-sensitivity observations, performed with the Low Frequency Array at 144 MHz and with the upgraded Giant Metrewave Radio Telescope at 400 MHz and 675 MHz. To these, we add two Very Large Array archival observations at 1400 and 4700 MHz. In the new observations, we detect a second pair of larger lobes and three regions with a filamentary morphology. We analyse the spectral index trend in the inner remnant lobes and see systematic steeper values at the lower frequencies compared to the GHz ones. Steeper spectral indices are found in the newly detected outer lobes (up to 2.1), as expected if they trace a previous phase of activity of the AGN. However, the differences between the spectra suggest different dynamical evolution within the intragroup medium during their expansion and/or different magnetic field values. We place constraints on the age of the inner and outer lobes and derive the duty cycle of the source. This results in a total active time of $\sim$39%. The filamentary structures have a steep spectral index ($\sim$1) without any spectral index trend and only one of them shows a steepening in the spectrum. Their origin is not yet clear, but they may have formed due to the compression of the plasma or due to magnetic field substructures

Methyl 3-(4-methoxy­phen­yl)-1-methyl-1,2,3,3a,4,11b-hexa­hydro­benzo[f]chromeno[4,3-b]pyrrole-3a-carboxyl­ate

In the title compound, C25H25NO4, the pyrrolidine ring exhibits an envelope conformation and the tetra­hydro­pyran ring exhibits a half-chair conformation. The crystal structure is stabilized by inter­molecular C–H⋯π inter­actions

Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity

A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers were previously synthesized and the potential anti-inflammatory and antinociceptive activities of these compounds were evaluated in vivo. The compounds displayed a very good activity against both carrageenan-induced hyperalgesia and oedema in the rat paw test. Therefore, in a very preliminary test, compounds (8a,b) showed antiproliferative activity in the HaCaT (aneuploid immortal keratinocyte from adult human skin) cell models. On these basis, our research continued with the synthesis of fluorinated derivatives (8c,d, 9b-d, and 10b-d) with the aim of improving the pharmacokinetic profile of the previous active compounds. Substitution of a hydrogen atom by a fluorine atom may change the conformational preferences of the molecules due to stereoelectronic effects and also fluorine atom may be able to exert the metabolic obstruction reducing the "first-pass effect". Compound 10b exhibited a prominent in vivo anti-inflammatory and antinociceptive activities, in addition its antiproliferative power in an in vitro model of human skin cancer is herein described

Synthesis and biological evaluation of fluorinated 1,5-diarylpyrrole-3-alkoxyethyl ether derivatives as selective COX-2 inhibitors endowed with anti-inflammatory activity

A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers were previously synthesized and the potential anti-inflammatory and antinociceptive activities of these compounds were evaluated in vivo. The compounds displayed a very good activity against both carrageenan-induced hyperalgesia and oedema in the rat paw test. Therefore, in a very preliminary test, compounds (8a,b) showed antiproliferative activity in the HaCaT (aneuploid immortal keratinocyte from adult human skin) cell models. On these basis, our research continued with the synthesis of fluorinated derivatives (8c,d, 9b-d, and 10b-d) with the aim of improving the pharmacokinetic profile of the previous active compounds. Substitution of a hydrogen atom by a fluorine atom may change the conformational preferences of the molecules due to stereoelectronic effects and also fluorine atom may be able to exert the metabolic obstruction reducing the "first-pass effect". Compound 10b exhibited a prominent in vivo anti-inflammatory and antinociceptive activities, in addition its antiproliferative power in an in vitro model of human skin cancer is herein described

A class of pyrrole derivatives endowed with analgesic/anti-inflammatory activity

We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules

A MeerKAT-meets-LOFAR study of Abell 1413: a moderately disturbed non-cool-core cluster hosting a ∼500\sim 500 kpc 'mini'-halo

Many relaxed cool-core clusters host diffuse radio emission on scales of hundreds of kiloparsecs: mini-haloes. However, the mechanism responsible for generating them, as well as their connection with central active galactic nuclei, is elusive and many questions related to their physical properties and origins remain unanswered. This paper presents new radio observations of the galaxy cluster Abell 1413 performed with MeerKAT (L-band; 872 to 1712 MHz) and LOFAR HBA (120 to 168 MHz) as part of a statistical and homogeneous census of mini-haloes. Abell 1413 is unique among mini-halo clusters as it is a moderately-disturbed non-cool-core cluster. Our study reveals an asymmetric mini-halo up to 584 kpc in size at 1283 MHz, twice as large as first reported at similar frequencies. The spectral index is flatter than previously reported, with an integrated value of $\alpha = -1.01 \pm 0.06$, shows significant spatial variation, and a tentative radial steepening. We studied the point-to-point X-ray/radio surface brightness correlation to investigate the thermal/non-thermal connection: our results show a strong connection between these components, with a super-linear slope of $b = 1.63 \pm 0.10$ at 1283 MHz and $b = 1.20 \pm 0.12$ at 145 MHz. We also explore the X-ray surface brightness/radio spectral index correlation, finding a slope of $b = 0.59 \pm 0.11$. Both investigations support the evidence of spectral steepening. Finally, in the context of understanding the particle acceleration mechanism, we present a simple theoretical model which demonstrates that hybrid scenarios - secondary electrons (re-)accelerated by turbulence - reproduce a super-linear correlation slope.Comment: 19 pages, 11 figures, 4 tables. Accepted for publication in MNRA

Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors

We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. © 2013 Elsevier Ltd. All rights reserved