The pathophysiology of osteoarthritis (OA) includes the destruction of subchondral bone tissue and inflammation of the synovium. Thus, an effective disease-modifying treatment should act on both of ...these pathogenetic components. It is known that cSrc kinase is involved in bone and cartilage remodeling, and SYK kinase is associated with the inflammatory component. Thus the aim of this study was to characterize the mechanism of action and efficacy of a small molecule multikinase inhibitor MT-SYK-03 targeting SYK and cSrc kinases among others in different in vitro and in vivo arthritis models. The selectivity of MT-SYK-03 kinase inhibition was assayed on a panel of 341 kinases. The compound was evaluated in a set of in vitro models of OA and in vivo OA and RA models: surgically-induced arthritis (SIA), monosodium iodoacetate-induced arthritis (MIA), collagen-induced arthritis (CIA), adjuvant-induced arthritis (AIA). MT-SYK-03 inhibited cSrc and SYK with IC
of 14.2 and 23 nM respectively. Only five kinases were inhibited > 90% at 500 nM of MT-SYK-03. In in vitro OA models MT-SYK-03 reduced hypertrophic changes of chondrocytes, bone resorption, and inhibited SYK-mediated inflammatory signaling. MT-SYK-03 showed preferential distribution to joint and bone tissue (in rats) and revealed disease-modifying activity in vivo by halving the depth of cartilage erosion in rat SIA model, and increasing the pain threshold in rat MIA model. Chondroprotective and antiresorptive effects were shown in a monotherapy regime and in combination with methotrexate (MTX) in murine and rat CIA models; an immune-mediated inflammation in rat AIA model was decreased. The obtained preclinical data support inhibition of cSrc and SYK as a viable strategy for disease-modifying treatment of OA. A Phase 2 clinical study of MT-SYK-03 is to be started.
•The largest data set of cloud tracked winds – about 0.5 million vectors – from the VMC/Venus Express imaging.•Characterization of the mean circulation at the Venus cloud tops.•Orbit-to-orbit changes ...and diurnal variations of the mean flow.•Long-term trend: acceleration of the mean flow from 2006 to 2012.•Periodicities in the cloud top wind field.
Six years of continuous monitoring of Venus by European Space Agency’s Venus Express orbiter provides an opportunity to study dynamics of the atmosphere our neighbor planet. Venus Monitoring Camera (VMC) on-board the orbiter has acquired the longest and the most complete so far set of ultra violet images of Venus. These images enable a study the cloud level circulation by tracking motion of the cloud features. The highly elliptical polar orbit of Venus Express provides optimal conditions for observations of the Southern hemisphere at varying spatial resolution. Out of the 2300 orbits of Venus Express over which the images used in the study cover about 10 Venus years. Out of these, we tracked cloud features in images obtained in 127 orbits by a manual cloud tracking technique and by a digital correlation method in 576 orbits. Total number of wind vectors derived in this work is 45,600 for the manual tracking and 391,600 for the digital method. This allowed us to determine the mean circulation, its long-term and diurnal trends, orbit-to-orbit variations and periodicities. We also present the first results of tracking features in the VMC near-IR images. In low latitudes the mean zonal wind at cloud tops (67±2km following: Rossow, W.B., Del Genio, A.T., Eichler, T. 1990. J. Atmos. Sci. 47, 2053–2084) is about 90m/s with a maximum of about 100m/s at 40–50°S. Poleward of 50°S the average zonal wind speed decreases with latitude. The corresponding atmospheric rotation period at cloud tops has a maximum of about 5days at equator, decreases to approximately 3days in middle latitudes and stays almost constant poleward from 50°S. The mean poleward meridional wind slowly increases from zero value at the equator to about 10m/s at 50°S and then decreases to zero at the pole. The error of an individual measurement is 7.5–30m/s. Wind speeds of 70–80m/s were derived from near-IR images at low latitudes. The VMC observations indicate a long term trend for the zonal wind speed at low latitudes to increase from 85m/s in the beginning of the mission to 110m/s by the middle of 2012. VMC UV observations also showed significant short term variations of the mean flow. The velocity difference between consecutive orbits in the region of mid-latitude jet could reach 30m/s that likely indicates vacillation of the mean flow between jet-like regime and quasi-solid body rotation at mid-latitudes. Fourier analysis revealed periodicities in the zonal circulation at low latitudes. Within the equatorial region, up to 35°S, the zonal wind show an oscillation with a period of 4.1–5days (4.83days on average) that is close to the super-rotation period at the equator. The wave amplitude is 4–17m/s and decreases with latitude, a feature of the Kelvin wave. The VMC observations showed a clear diurnal signature. A minimum in the zonal speed was found close to the noon (11–14h) and maxima in the morning (8–9h) and in the evening (16–17h). The meridional component peaks in the early afternoon (13–15h) at around 50°S latitude. The minimum of the meridional component is located at low latitudes in the morning (8–11h). The horizontal divergence of the mean cloud motions associated with the diurnal pattern suggests upwelling motions in the morning at low latitudes and downwelling flow in the afternoon in the cold collar region.
The properties of the complexes I–@C60(OH)20 and I–@C60(OH)30 have been determined using the quantum chemical DFT PBE0 method to assess the possibility of synthesis of highly hydroxylated fullerene ...endo-iodides for the use in radiotherapy of different organs. The arrangement of the hydroxyl groups corresponds to the location of halogen atoms in (D 5d)-C60F20 and (D 3d)-C60Cl30. Negative-charged iodine is localized in the center of the fullerene cavity and has no significant influence on the IR spectra of hydroxylated fullerenes. The exothermic effect of iodide anion encapsulation in C60(OH) n (0.33 eV at n = 20; 0.03 eV at n = 30) is smaller than in C60 (0.78 eV). The energies of the lower excited singlet states computed by the TD DFT method for I–@C60(OH) n (2.11 eV at n = 20; 1.77 eV at n = 30) are larger than those for I–@C60 (1.36 eV). They indicate a low reactivity, making it possible to synthesize such complexes for medical use.
A quantum-chemical model of the minimal cluster in xenotime has been proposed taking into account the ionic-crystal medium potential. The YO
8
5–
cluster includes oxygen atoms from six phosphate ...anions. Owing to the breaking of the covalent P–O bonds, each oxygen atom contributes one unpaired electron to the cluster. The spin state is characterized by a zero ‹Ŝ› vector and a doubled dispersion
D
= 2 (‹Ŝ
2
› – ‹Ŝ›
2
) = 7.98 a. u. Structure of the YO
8
5–
cluster does not favour the replacement of yttrium(III) with thorium(III) or uranium(III). The simulations have been performed via the DFT method using the (U)PBE0 functional.
Winds derived by a digital tracking technique from ultraviolet (365 nm) images captured by the Venus Monitoring Camera (VMC) onboard the Venus Express spacecraft from 2006 to 2013 were used to study ...the atmospheric circulation at cloud top level (70 ± 2 km). This data set allows variations of the wind speed with both latitude and longitude to be studied and establishes their correlation with surface topography as well as local time dependence. Both zonal and meridional wind components show some correlation with topography. The minimum zonal wind speed was found at noon above Ovda Regio (10°S, 93°E), the highest region of Aphrodite Terra, one of the largest highlands in the equatorial region. The area of slow zonal wind extends to at least 30°S and shifts in the direction of superrotation in the afternoon and with increasing latitude (poleward). The observed deceleration of cloud top wind was recently attributed to the interaction of the gravity (mountain) waves generated by Aphrodite Terra with the atmospheric circulation. The present study was performed for different local time over the mountainous longitudes. The deceleration pattern in the zonal wind field is mainly conserved within a few hours around noon. Systematic longitude shift is observed in the afternoon in the direction of the evening terminator. Another area of perturbation of both zonal and meridional wind components is observed in the equatorial region around LT = 13–14 hr and may be explained by the solar tide.
Plain Language Summary
Venus is completely covered with a thick cloud layer with its top at about 70 km. Surprisingly, recent observations show that the cloud level circulation is affected by the surface topography. In this paper we analyzed wind velocities derived from tracking of cloud features in the UV images acquired by the Venus Monitoring Camera onboard the European Space Agency's Venus Express orbiter during its operations from 2006 to 2013. The zonal wind at the cloud top decelerates by about 20% above the highest part of Aphrodite Terra and reaches its minimum at local noon. The zonal wind deceleration is explained by interaction of gravity waves generated by the surface relief with the atmospheric circulation. An additional deceleration occurs in the afternoon in the equatorial region and is probably caused by solar heating of the clouds. The combination of both effects results in a vast area of slow wind during the daytime.
Key Points
A maximum deceleration of the mean zonal flow is observed at noon above the highest region of Aphrodite Terra, Venus
The mean zonal and meridional flows at cloud top level in the equatorial region are perturbed by a solar tide at 13–14 hr
A dependence of the mean zonal and meridional flows on topography is observed from the equator to at least 30°S
We present more than 250,000 wind vectors derived from the visible (513 nm) images captured by the Venus Monitoring Camera (VMC) onboard ESA's Venus Express orbiter in the Southern hemisphere from 01 ...July 2007 to 29 January 2013. From comparison to the wind velocity derived from tracking of the descent probes, these measurements correspond to 60 ± 3 km altitude, being between two levels 70 ± 2 km and 55 ± 2 km, probed by VMC in ultraviolet (UV) (365 nm) and NIR (965 nm) channels, respectively. The mean zonal wind suggests retrograde circulation with mean zonal wind speed decreasing from 76.5 to 61.5 m/s at 30°–65°S. In low latitudes, 10–20°S, it increased to 82 m/s over the course of the mission. The mean zonal flow depends on local solar time and latitude and is affected by the large‐scale topography. The meridional winds indicated equatorward flow of up to 7 m/s in the middle and low cloud opposite to that derived from simultaneous UV observations at the cloud top.
Plain Language Summary
Dynamics of the Venus atmosphere is dominated by a strong zonal retrograde circulation called “superrotation.” The physical mechanisms maintaining this unique regime are poorly understood due to insufficient observational data. For about eight years, the Venus Monitoring Camera onboard ESA's Venus Express orbiter monitored motions of the cloud features in three spectral ranges: ultraviolet (UV) (365 nm), visible (513 nm), and near‐infrared (915 nm). These wavelengths probed different altitudes: 70 ± 2 km, 60 ± 3 km, and 55 ± 2 km correspondingly, thus providing wind field tomography. In this paper, we present more than 250,000 wind vectors derived from the visible images. The results suggest decrease of the retrograde mean zonal wind speed from 76.5 to 61.5 m/s at 30°–65°S, and its increase up to 82 m/s at 10–20°S and show pronounced variations with local solar time, latitude, and surface topography. Interestingly, the meridional winds indicate equatorward flow of up to 7 m/s in the deep cloud opposite to that previously derived from UV images at the cloud top.
Key Points
More than 250,000 wind vectors at 57–63 km altitude were derived from the images taken by the Venus Monitoring Camera /Venus Express visible (513 nm) channel
Mean zonal wind speed accelerated by ∼18.5 m/s at 30 ± 5°S over 8 Venusian years
Zonal wind speed decreased from 85 m/s at the equator to 35 m/s at 80°S, meridional wind of up to 7 m/s velocity is directed equatorward
Forced mode locking in a semiconductor laser Zakharyash, V F; Klement’ev, V M; Titov, E A
Journal of physics. Conference series,
11/2021, Letnik:
2067, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
A brief description of the theory of mode locking of a semiconductor laser when the modulating generator frequency is close to the intermode frequency is given. It is shown that during mode ...locking there is phase locking, due to which the dispersion of summed intensity in the interpulse interval tends to zero.
The work describes a one-dimensional detector for diffraction experiments at a synchrotron radiation beam. The detector is being developed at the Budker Institute of Nuclear Physics, Siberian Branch, ...Russian Academy of Sciences. Until recently the institute was developing gas one-coordinate detectors, in particular a one-coordinate detector with calculated channels (OD-3M), based on the technology of multiwire proportional chambers. To provide a spatial resolution better than 100 microns at a photon energy in a wide energy range (3–30 keV), it is necessary to use solid-state microstrip or matrix sensors in combination with specialized integrated registration circuits. The developed SOCOD detector, using a microstrip sensor based on gallium arsenide as a registration element, operates in the mode of the direct counting of photons with an energy of more than 3–4 keV and a speed of up to 1 MHz/channel. The work gives a general description of the current version of the detector, a block diagram of the registration channel, the software allowing users to control the operation of the detector and display the results obtained, and the developed algorithm for leveling the trigger thresholds in the channels. The results of electronic tests, the work of the alignment algorithm and their discussion are presented.
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