Although RAF kinases are critical for controlling cell growth, their mechanism of activation is incompletely understood. Recently, dimerization was shown to be important for activation. Here we show ...that the dimer is functionally asymmetric with one kinase functioning as an activator to stimulate activity of the partner, receiver kinase. The activator kinase did not require kinase activity but did require N-terminal phosphorylation that functioned allosterically to induce cis-autophosphorylation of the receiver kinase. Based on modeling of the hydrophobic spine assembly, we also engineered a constitutively active mutant that was independent of Ras, dimerization, and activation-loop phosphorylation. As N-terminal phosphorylation of BRAF is constitutive, BRAF initially functions to activate CRAF. N-terminal phosphorylation of CRAF was dependent on MEK, suggesting a feedback mechanism and explaining a key difference between BRAF and CRAF. Our work illuminates distinct steps in RAF activation that function to assemble the active conformation of the RAF kinase.
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•RAF dimers are asymmetric with one component allosterically activating the other•N-terminal phosphorylation but not kinase activity is required on the activator•Dimerization induces cis-autophosphorylation of the RAF activation loop•Mutations that stabilize the active conformation do not require dimerization
RAF kinase dimerization is important for its activation. Dimerization allosterically induces the active kinase conformation through the asymmetric phosphorylation of the activation loop on one molecule, which activates the second molecule by inducing its cis-autophosphorylation.
Russia's rapid transition from a closed to an open economy occurred at the beginning of the post-Soviet period and within the Soviet framework of production. This resulted in the deindustrialization ...of the Russian economy, which has had many negative effects, including capital flight, the loss of manufacturing, and an increase in the import of manufactured products. This article considers the primary challenges to the reindustrialization of the Russian economy, and argues that this process must involve government subsidies, especially for the creation of vertically integrated interindustry corporations (VIICs). VIICs have long production-technology chains that begin with the extractive industries and end with process manufacturing enterprises. The creation of VIICs and the introduction of new technology will make Russian manufactured products more competitive both domestically and internationally. The problems facing Russian manufacturing and the ways in which VIICs can help address these problems are analyzed on the basis of five groups of producers: 1) the key producers of investment mechanical engineering; 2) the industry producers of investment mechanical engineering; 3) producers of manufactured products intended for industrial consumption; 4) producers of consumer goods; and 5) the producers of high-tech durable goods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Laser induced dielectric breakdown (LIDB) on a surface of solid Mo in H
2
/BF
3
atmosphere at 30–760 Torr and in a gaseous mixture MoF
6
/H
2
/BF
3
+ at 760 Torr pressure is tested for synthesis and ...deposition of superhard molybdenum borides that are needed in many areas of industry and technology. The emission spectra of the plasma and the dynamics of the gas discharge near the substrate are investigated. A comparative analysis of the gas mixture before and after exposure to LIDB plasma is carried out using IR spectroscopy. The conditions for the formation of molybdenum borides are determined. A thermodynamic analysis of the MoF
6
/H
2
/BF
3
and Mo/H
2
/BF
3
systems is carried out to determine the temperature range for the formation of molybdenum borides and establish the main chemical reactions responsible for their formation. Deposits containing MoB and MoB
2
phases are obtained. For the mixture MoF
6
/H
2
/BF
3
, the deposit exhibits an amorphous layered structure, which contains 19.15 wt% F, 30.45% O, and 0.8% Si. For the Mo/H
2
/BF
3
system at the pressures 30 and 160 Torr, nanopowder of molybdenum boride is produced with a characteristic grain size of 100 nm. At pressures above 160 Torr, Mo nanopowder with a grain size < 30 nm is obtained.
Abstract
In light of directives around the world to eliminate toxic materials in various technologies, finding lead-free materials with high piezoelectric responses constitutes an important current ...scientific goal. As such, the recent discovery of a large electromechanical conversion near room temperature in (1−
x
)Ba(Zr
0.2
Ti
0.8
)O
3
−
x
(Ba
0.7
Ca
0.3
)TiO
3
compounds has directed attention to understanding its origin. Here, we report the development of a large-scale atomistic scheme providing a microscopic insight into this technologically promising material. We find that its high piezoelectricity originates from the existence of large fluctuations of polarization in the orthorhombic state arising from the combination of a flat free-energy landscape, a fragmented local structure, and the narrow temperature window around room temperature at which this orthorhombic phase is the equilibrium state. In addition to deepening the current knowledge on piezoelectricity, these findings have the potential to guide the design of other lead-free materials with large electromechanical responses.
Ab initio simulations and experimental techniques are combined to reveal that, unlike what was commonly accepted for more than 30 years, perovskites and related materials enhance their ...ferroelectricity as hydrostatic pressure increases above a critical value. This unexpected high-pressure ferroelectricity is different in nature from conventional ferroelectricity because it is driven by an original electronic effect rather by long-range interactions.
An energetic expression containing four different macroscopic terms is proposed to explain and understand coupled magnetic orders (and the directions of the simultaneously occurring ferromagnetic ...and/or antiferromagnetic vectors) in terms of anti-phase and/or in-phase tilting of oxygen octahedra in magnetic and multiferroic perovskites. This expression is derived from a suggested simple microscopic formula, and has its roots in the Dzyaloshinsky-Moriya interaction. Comparison with data available in the literature and with first-principles calculations we conduct here confirms the validity of such a simple and general law for any tested structural paraelectric and even ferroelectric phase, and for any chosen direction of any selected primary magnetic vector.
Abstract A low-current gliding discharge (current range 1–5 A) in high-speed air flows of 100–250 m s −1 was experimentally studied. A high-voltage direct current source with a maximum voltage of 4.5 ...kV was used to create the discharge. The average electron concentration n e ∼ 10 14 cm −3 and the plasma ionization degree were determined by measuring the Stark broadening of the hydrogen H β line ( λ H β = 486.1 nm). The estimates of the electric field ( E ∼ 100 V cm −1 ÷ 600 V cm −1 ) in the discharge positive column were found using time-synchronized high-speed video recordings and oscillograms. The gas rotational temperature T g = 7000–9500 K and the vibrational temperature T v = 7000–11 000 K were estimated using optical emission spectroscopy. Time-resolved spectroscopy is used to investigate the effective plasma channel spatial regions from which the N, NH, N 2 + , O and OH molecules radiate. The difference of the obtained radii indicates the presence of a radial temperature gradient and inhomogeneous plasma composition in the discharge cross section. The possibility of using of gliding discharge to ignite hydrocarbon-air mixtures in the ramjet engines combustors has been experimentally demonstrated.
The Wang-Landau Monte Carlo algorithm is implemented within an effective Hamiltonian approach and applied to BaTiO sub(3) bulk. The density of states obtained by this approach allows a highly ...accurate and straightforward calculation of various thermodynamic properties, including phase transition temperatures, as well as polarization, dielectric susceptibility, specific heat, and electrocaloric coefficient at any temperature. This approach yields rather smooth data even near phase transitions and provides direct access to entropy and free energy, which allow us to compute properties that are typically unaccessible by atomistic simulations. Examples of such latter properties are the nature (i.e., first order versus second order) of the phase transitions for different supercell sizes and the thermodynamic limit of the Curie temperature and latent heat.
Using the Fourier method, we obtain necessary and sufficient conditions for the existence of a classical solution of the mixed problem for a homogeneous wave equation with summable potential and ...fixed endpoints and also obtain an explicit representation of the solution in the form of a rapidly converging series.
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