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- Chockalingam, P. S., et al.
(författare)
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Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 315-323
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate aggrecanase activity after traumatic knee injury in a rat model by measuring the level of aggrecanase-generated Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments in synovial fluid, and compare with ARG-aggrecan release into joint fluid following human knee injury. To evaluate the effect of small molecule inhibitors on induced aggrecanase activity in the rat model. Method: An enzyme-linked immunosorbent assay (ELISA) was developed to measure ARG-aggrecan levels in animal and human joint fluids. A rat model of meniscal tear (MT)-induced joint instability was used to assess ARG-aggrecan release into joint fluid and the effects of aggrecanase inhibition. Synovial fluids were also obtained from patients with acute joint injury or osteoarthritis and assayed for ARG-aggrecan. Results: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG-aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG-aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. Conclusions: Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 3. |
- López, A., et al.
(författare)
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Laboratory characterization and astrophysical detection of vibrationally excited states of vinyl cyanide in Orion-KL
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 572
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Tidskriftsartikel (refereegranskat)abstract
- Context. We perform a laboratory characterization in the 18–1893 GHz range and astronomical detection between 80–280 GHz in Orion-KL with IRAM-30 m of CH2CHCN (vinyl cyanide) in its ground and vibrationally excited states. Aims. Our aim is to improve the understanding of rotational spectra of vibrationally excited vinyl cyanide with new laboratory data and analysis. The laboratory results allow searching for these excited state transitions in the Orion-KL line survey. Furthermore, rotational lines of CH2CHCN contribute to the understanding of the physical and chemical properties of the cloud. Methods. Laboratory measurements of CH2CHCN made on several different frequency-modulated spectrometers were combined into a single broadband 50–1900 GHz spectrum and its assignment was confirmed by Stark modulation spectra recorded in the 18–40 GHz region and by ab-initio anharmonic force field calculations. For analyzing the emission lines of vinyl cyanide detected in Orion-KL we used the excitation and radiative transfer code (MADEX) at LTE conditions. Results. Detailed characterization of laboratory spectra of CH2CHCN in nine different excited vibrational states: ?11 = 1, ?15 = 1, 2) ⇔ (?10 = 1,?15 = 1) ⇔ (?11 = 1,?14 = 1), and ?11 = 4 are determined, as well as the detection of transitions in the ?11 = 2and ?11 = 2, ?10 = 1 ⇔ (?11 = 1,?15 = 1), ?11 = 3/?15 = 2/?14 = 1, (?11 = 1,?10 = 1) ⇔ (?11 = 2,?15 = 1), ?9 = 1, (?11 = 1,?15 = The rotational transitions of the ground state of this molecule emerge from four cloud components of hot core nature, which trace the ?11 = 3 states for the first time in Orion-KL and of those in the ?10 = 1 ⇔ (?11 = 1,?15 = 1) dyad of states for the first time in space. physical and chemical conditions of high mass star forming regions in the Orion-KL Nebula. The lowest energy vibrationally excited states of vinyl cyanide, such as ?11 = 1 (at 328.5 K), ?15 = 1 (at 478.6 K), ?11 = 2 (at 657.8 K), the ?10 = 1 ⇔ (?11 = 1,?15 = 1) dyad (at 806.4/809.9 K), and ?11 = 3 (at 987.9 K), are populated under warm and dense conditions, so they probe the hottest parts of the Orion-KL source. The vibrational temperatures derived for the ?11 = 1, ?11 = 2, and ?15 = 1 states are 252 ± 76K, 242 ± 121K, column density of CH2CHCN in the ground state is (3.0 ± 0.9) × 1015 cm−2. We report the detection of methyl isocyanide (CH3NC) and 227 ± 68K, respectively; all of them are close to the mean kinetic temperature of the hot core component (210K). The total for the first time in Orion-KL and a tentative detection of vinyl isocyanide (CH2CHNC). We also give column density ratios between the cyanide and isocyanide isomers, obtaining a N(CH3NC)/N(CH3CN) ratio of 0.002. Conclusions. Laboratory characterization of many previously unassigned vibrationally excited states of vinyl cyanide ranging from microwave to THz frequencies allowed us to detect these molecular species in Orion-KL. Column density, rotational and vibrational temperatures for CH2CHCN in their ground and excited states, and the isotopologues have been constrained by means of a sample of more than 1000 lines in this survey.
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