To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ ...in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM).
Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450–500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction.
The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results.
Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.
Changing-look (CL) quasars are a newly discovered class of luminous active galactic nuclei that undergo rapid ( 10 yr) transitions between Type 1 and Type 1.9/2, with an associated change in their ...continuum emission. We characterize the host galaxies of four faded CL quasars using broadband optical imaging. We use gri images obtained with the Gemini Multi-Object Spectrograph on Gemini North to characterize the surface brightness profiles of the quasar hosts and search for O iii λ4959, λ5007 emission from spatially extended regions, or voorwerpjes, with the goal of using them to examine past luminosity history. Although we do not detect, voorwerpjes surrounding the four quasar host galaxies, we take advantage of the dim nuclear emission to characterize the colors and morphologies of the host galaxies. Three of the four galaxies show morphological evidence of merger activity or tidal features in their residuals. The three galaxies that are not highly distorted are fit with a single Sérsic profile to characterize their overall surface brightness profiles. The single-Sérsic fits give intermediate Sérsic indices between the n = 1 of disk galaxies and the n = 4 of ellipticals. On a color-magnitude diagram, our CL quasar host galaxies reside in the blue cloud, with other active galactic nucleus (AGN) host galaxies and star-forming galaxies. On a color-Sérsic index diagram the CL quasar hosts reside with other AGN hosts in the "green valley." Our analysis suggests that the hosts of CL quasars are predominantly disrupted or merging galaxies that resemble AGN hosts, rather than inactive galaxies.
Middle Holocene cultures have been widely studied around the Eastern-Mediterranean basin in the last 30 years and past cultural activities have been commonly linked with regional climate changes. ...However, in many cases such linkage is equivocal, in part due to existing climatic evidence that has been derived from areas outside the distribution of ancient settlements, leading to uncertainty from complex spatial heterogeneity in both climate and demography. A few high-resolution well-dated paleoclimate records were recently established using speleothems in the Central and Eastern-Mediterranean basin, however, the scarcity of such records in the western part of the Mediterranean prevents us from correlating past climate evolutions across the basin and deciphering climate–culture relation at fine timescales. Here we report the first decadal-resolved Mid-Holocene climate proxy records from the Western-Mediterranean basin based on the stable carbon and oxygen isotopes analyses of two U/Th dated stalagmites from the Gueldaman GLD1 Cave in Northern Algeria. Comparison of our records with those from Italy and Israel reveals synchronous (multi) centennial dry phases centered at ca. 5600, ca. 5200 and ca. 4200 yr BP across the Mediterranean basin. New calibrated radiocarbon dating constrains reasonably well the age of rich anthropogenic deposits (e.g., faunal remains, pottery, charcoal) excavated inside the cave, which allows the comparison between in situ evidence of human occupation and of climate change. This approach shows that the timing of a prolonged drought at ca. 4400–3800 yr BP blankets the onset of cave abandonment shortly after ca. 4403 cal yr BP, supporting the hypothesis that a climate anomaly may have played a role in this cultural disruption.
•The SBSE–TD–GC–MS is a solvent-less, simple and fast analytical method.•The method simplifies sample preparation and extraction of off-flavors in fish tissue.•The method is suitable for monitoring ...off-flavors in depuration of salmon fish.
A sensitive and solvent-less method for the determination of musty and earthy off-flavor compounds, 2-methylisoborneol (MIB) and geosmin (GSM), in salmon tissue was developed using stir bar sorptive extraction–thermal desorption coupled with gas chromatography–mass spectrometry (SBSE–TD–GCMS). MIB and GSM were solid phase extracted using polydimethylsiloxane (PDMS) coated stir bars, analyzed by gas chromatography, and detected in full scan mode of mass selective detector (MSD). Using this method, the calibration curves of MIB and GSM were linear in the range of 0.3–100ng/L, with a correlation coefficient above 0.999 and RSDs less than 4% (n=4). The limit of detection (LOD, S/N=3, n=6) and limit of quantification (LOQ, S/N=10, n=6) of MIB and GSM were both ∼0.3 and 1ng/L, respectively. The recoveries of MIB and GSM were 22% and 29% by spike in 30ng/L standard compounds, 23% and 30% by spike-in 100ng/L standard compounds in salmon tissue samples with good precision (<8% of RSDs, n=6), respectively. The recoveries of MIB and GSM were better than reported methodologies using SPME fibres (<10%) in fish tissue samples. This method was successfully applied to monitor and characterize depurated salmon fillet samples (0, 3, 6 and 10 days).
Clinical therapeutic studies using (225)Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of ...(225)Ac. The purpose of this study was to determine the amount of (225)Ac and non-equilibrium progeny in the mouse kidney after the injection of (225)Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with (225)Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess (213)Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess (213)Bi reaching the kidney (γ-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq(-1), of which 0.46 (SD 0.16) Gy kBq(-1) (i.e. 60%) was due to non-equilibrium excess (213)Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from non-equilibrium excess (213)Bi (0.31 (SD 0.11) Gy kBq(-1)) represented ∼46% of the total. For the medulla the dose contribution from excess (213)Bi (0.81 (SD 0.28) Gy kBq(-1)) was ∼80% of the total. Based on these estimates, for human patients we project a kidney-absorbed dose of 0.28 Gy MBq(-1) following administration of (225)Ac-huM195 with non-equilibrium excess (213)Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of (225)Ac radioimmunotherapy.
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•Special requirements in pulsed fast-neutron detection of prompt fission and fusion devices call for special detection detector or system having a flat energy response, a high ...signal-noise-ratio, proper threshold energy, and a good radiation resistance, which is successfully satisfied by the detection system mentioned in the paper.•A fast-neutron detection system based on a thin silicon carbide detector and a 237 Np fission target was developed with a threshold of 0.4 MeV, flat energy response and high signal-to-noise ratio.•A neutron detection system was calibrated on nuclear reactor and got good fission fragment spectra.•The developed SiC neutron detectors are ideally suited for neutron detection not only for good endurance in high-temperature and high- radiation environments, but also for low response to background radiation derived from its thin sensitive volume.•The neutron detection system provides a useful tool for fast-neutron fluence monitoring in nuclear fission and fusion equipment, especially in high-temperature and high- radiation environments.
Special requirements in pulsed fast-neutron detection of prompt fission and fusion devices call for a detection detector or system which could detect fast-neutrons in a severe radiation field, and thus should necessarily have a flat energy response, a high signal-noise-ratio, proper threshold energy, and a good radiation resistance. In this paper, a fast-neutron detection system based on a thin silicon carbide (SiC) detector and a 237Np fission target was developed and tested on Xi’an Pulsed Reactor, which was with a neutron threshold of 0.4 MeV, a flat energy response to neutrons in the range of 1MeV to 20MeV and got good response spectra to fission fragments. The SiC detector used here is a 4H-SiC Schottky diode detector with the dimension of 20mm×20mm×20μm, a dark current of lower than 5nA within 600V, a best energy resolution to alpha particles of about 1.78% and a high radiation resistance under alpha particle irradiation with a max incident number of 1.03×1010. The detection system shows advantaged prospects in fast-neutron fluence monitoring in nuclear fission and fusion equipments.
Large eddy simulations (LES) of a scramjet combustor are reported in this paper. The case under study is a cavity-based combustion chamber that is experimentally studied at the US Air Force Research ...Laboratory. The chamber is fed by eleven injectors. The computational domains are either simplified including only one or two injectors or complete with the 11 injectors. A good agreement is found between experimental data (velocities measured by PIV) and results from the LES if the kinetic used is chosen with care. A high temperature is found inside the cavity promoting a reactive zone located in the mixing layer where the flow velocity is high. At this location, the combustion occurs first in a diffusion dominated regime followed by the efficient burning of a well mixed mixture (rich then lean). A significant diffusion dominated burning is also found inside the cavity, mostly at the interface between the two recirculation zones. The simulation of the complete geometry revealed a transverse phenomenon on the temperature and mixing fields, but which had nevertheless little effect on the comparison with the available experimental data. A tabulation of the chemistry based on a premixed flamelet library without compressibility effects has been tested a priori on the results of the simulation with one injector. Good results on temperature and
H
2
O
fields are found. Significant localized discrepancies appeared on CO and
CO
2
fields due to the complexity of the combustion regimes, while compressibility effects were found to be weak for the configuration studied.
CONTEXT St John's wort is a popular herbal product used to treat depression
but it has been implicated in drug interactions. OBJECTIVE To assess the potential of St John's wort administration to ...alter the
activity of the cytochrome P450 (CYP) enzymes extensively involved in drug
metabolism. DESIGN, SETTING, AND PARTICIPANTS Open-label crossover study with fixed treatment order conducted March
2002 to February 2003 in a US general clinical research center involving 12
healthy volunteers (6 men and 6 women) aged 22 to 38 years before and after
14 days of administration of St John's wort. INTERVENTION Participants were given probe drugs (30 mg of dextromethorphan and 2
mg of alprazolam) to establish baseline CYP 3A4 and CYP 2D6 activity. After
a minimum 7-day washout period, participants began taking one 300-mg tablet
3 times per day. After 14 days of St John's wort administration, participants
were given the probe drugs along with 1 St John's wort tablet to establish
postadministration CYP activity; the St John's wort dosing regimen was continued
for 48 hours. MAIN OUTCOME MEASURES Changes in plasma pharmacokinetics of alprazolam as a probe for CYP
3A4 activity and the ratio of dextromethorphan to its metabolite, dextrorphan,
in urine as a probe for CYP 2D6 activity. RESULTS A 2-fold decrease in the area under the curve for alprazolam plasma
concentration vs time (P<.001) and a 2-fold increase
in alprazolam clearance (P<.001) were observed
following St John's wort administration. Alprazolam elimination half-life
was shortened from a mean (SD) of 12.4 (3.9) hours to 6.0 (2.4) hours (P<.001). The mean (SD) urinary ratio of dextromethorphan
to its metabolite was 0.006 (0.010) at baseline and 0.014 (0.025) after St
John's wort administration (P = .26). CONCLUSIONS A 14-day course of St John's wort administration significantly induced
the activity of CYP 3A4 as measured by changes in alprazolam pharmacokinetics.
This suggests that long-term administration of St John's wort may result in
diminished clinical effectiveness or increased dosage requirements for all
CYP 3A4 substrates, which represent at least 50% of all marketed medications.
Two 4H silicon carbide (SiC) radiation detectors based on Schottky diode were fabricated with high-quality lightly doped 4H-SiC epitaxial layer with sensitive volumes of 5 mm × 5 mm × 20 µm and 3 mm ...× 3 mm × 100 µm; their dark current were in the range of 0.3 pA to 63 nA at a bias voltage of 600 V. These detectors were used in detection of alpha particles (emitted by 237Np, 238Pu, 243Am and 244Cm source) and oxygen particles (generated by the HI-13 accelerator with energy of 86 MeV). The experiment results showed that both detectors worked stably with a charge collection efficiency nearly 99.3% and an energy resolution of 1%–3%, demonstrating their, wide application prospect in the detection of charged particles and especially in heavy charged particles.
► The elastic analysis model results confirm the Clarke model. ► A novel simple determination method of growth parameter is proposed and validated. ► The creep analysis model can precisely describe ...the realistic stress evolutions. ► We find Clarke model can be applied to case considering creep relaxation phenomena. ► The work serves as a basis for experimental work on stress measurement.
Considering the case of asymmetric oxidation, new elastic and creep analysis models are developed to elucidate the stress evolutions in an oxide scale/metal substrate system during isothermal oxidation, due to the oxidation growth strain in oxide scale. The theoretical works allow for the experimental inference of growth strain and stresses from the curvature measurements during oxidation. Moreover, they provide ways to explore and identify the main mechanisms for oxidation. Two sets of published experimental data are employed and analyzed by the elastic and creep analytical approaches. A novel simple determination method of the growth parameter is proposed and validated.
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