It is shown that well-know multicriteria optimization procedure using linear combination of partial target functionals may be characterized as non-stable from view-point of weights of partial target ...functionals in total linear sum of last ones. To improve stability of the procedure utilization of stabilizing functionals is suggested. The operation algorithm of system optimization realizing suggested method is described.
The structure, transformation and behaviour of C60 fullerene molecule is not sufficiently understood by the scientific community and was unresolved problem until the present day. This not provide a ...possibility of correct interpretation of its physical and chemical properties. In this work we have substantiated the advisability of consideration of pentatomic cycles in the C60 fullerene, as pentatomic molecules forming this frame. The mechanism of formation of the C60 fullerene frame from pentatomic molecules has been proposed. The levels of matter formation with description of fullerene production mechanism have been examined.
In this paper it is shown that a measurement of the relative luminosity changes at the LHC may be obtained by analysing the currents drawn from the high voltage power supplies of the electromagnetic ...section of the forward calorimeter of the ATLAS detector. The method was verified with a reproduction of a small section of the ATLAS forward calorimeter using proton beams of known beam energies and variable intensities at the U-70 accelerator at IHEP in Protvino, Russia. The experimental setup and the data taking during a test beam run in April 2008 are described in detail. A comparison of the measured high voltage currents with reference measurements from beam intensity monitors shows a linear dependence on the beam intensity. The non-linearities are measured to be less than 0.5 % combining statistical and systematic uncertainties.
Mitochondria produce over 90% of cellular ATP and actively participate in maintaining ion homeostasis, redox status, lipid metabolism, and cell growth. Changes in the matrix volume of mitochondria ...affect their functional and structural integrity. Modest volume increases associated with modulation of the inner mitochondrial membrane can activate electron transfer chain and oxidative phosphorylation, whereas excessive swelling impairs structural organization of the membrane and initiate mitochondria‐mediated cell death mechanisms. Therefore, clarifying the precise mechanisms of excessive mitochondrial swelling is important for regulation of mitochondria‐mediated cell death pathways in response to energy and oxidative stresses. Opening of non‐selective mitochondrial permeability transition pores (mPTP) is the primary cause of excessive matrix swelling. The molecular identity remains unknown and recent studies suggest the existence of two or more types of mPTP that can be composed of different protein(s). The adenine nucleotide translocator (ANT) and FOF1‐ATP synthase were proposed to be potential mPTP core components that can act together or independently each other. Here, we elucidated the role of ANT in mPTP opening by applying both experimental and computational approaches. mPTP opening was evaluated in cardiac mitochondria that were exposed to moderate and high Ca2+ concentrations in the absence and presence of respiratory substrates and ADP. We developed a detailed model of the ANT transport mechanism including the matrix (ANTM), cytosolic (ANTC), and pore (ANTP) states of the transporter that was able to simulate our experimental data. In addition, we corroborated and simulated our ANT model based on previous ANT kinetics data. The model was successful not only in simulating ANT pore state transition, but also explained the potential role of ANT in mPTP opening in cardiac mitochondria.
Mitochondrial metabolism and function are modulated by changes in matrix Ca
2+
. Small increases in the matrix Ca
2+
stimulate mitochondrial bioenergetics, whereas excessive Ca
2+
leads to cell death ...by causing massive matrix swelling and impairing the structural and functional integrity of mitochondria. Sustained opening of the non-selective mitochondrial permeability transition pores (PTP) is the main mechanism responsible for mitochondrial Ca
2+
overload that leads to mitochondrial dysfunction and cell death. Recent studies suggest the existence of two or more types of PTP, and adenine nucleotide translocator (ANT) and F
O
F
1
-ATP synthase were proposed to form the PTP independent of each other. Here, we elucidated the role of ANT in PTP opening by applying both experimental and computational approaches. We first developed and corroborated a detailed model of the ANT transport mechanism including the matrix (ANT
M
), cytosolic (ANT
C
), and pore (ANT
P
) states of the transporter. Then, the ANT model was incorporated into a simple, yet effective, empirical model of mitochondrial bioenergetics to ascertain the point when Ca
2+
overload initiates PTP opening via an ANT switch-like mechanism activated by matrix Ca
2+
and is inhibited by extra-mitochondrial ADP. We found that encoding a heterogeneous Ca
2+
response of at least three types of PTPs, weakly, moderately, and strongly sensitive to Ca
2+
, enabled the model to simulate Ca
2+
release dynamics observed after large boluses were administered to a population of energized cardiac mitochondria. Thus, this study demonstrates the potential role of ANT in PTP gating and proposes a novel mechanism governing the cryptic nature of the PTP phenomenon.
Graphical abstract
Optic atrophy-1 (OPA1) plays a crucial role in the regulation of mitochondria fusion and participates in maintaining the structural integrity of mitochondrial cristae. Here we elucidate the role of ...OPA1 cleavage induced by calcium swelling in the presence of Myls22 (an OPA1 GTPase activity inhibitor) and TPEN (an OMA1 inhibitor). The rate of ADP-stimulated respiration was found diminished by both inhibitors, and they did not prevent Ca2+-induced mitochondrial respiratory dysfunction, membrane depolarization, or swelling. L-OPA1 cleavage was stimulated at state 3 respiration; therefore, our data suggest that L-OPA1 cleavage produces S-OPA1 to maintain mitochondrial bioenergetics in response to stress.
Cells contain several apoptotic endonucleases, which appear to act simultaneously before and after cell death by destroying the host cell DNA. It is largely unknown how the endonucleases are being ...induced and whether they can regulate each other. This study was performed to determine whether apoptotic mitochondrial endonuclease G (EndoG) can regulate expression of other apoptotic endonucleases. The study showed that overexpression of mature EndoG in kidney tubular epithelial NRK-52E cells can increase expression of caspase-activated DNase (CAD) and four endonucleases that belong to DNase I group including DNase I, DNase X, DNase IL2, and DNase γ, but not endonucleases of the DNase 2 group. The induction of DNase I-type endonucleases was associated with DNA degradation in promoter/exon 1 regions of the endonuclease genes. These results together with findings on colocalization of immunostained endonucleases and TUNEL suggest that DNA fragmentation after EndoG overexpression was caused by DNase I endonucleases and CAD in addition to EndoG itself. Overall, these data provide first evidence for the existence of the integral network of apoptotic endonucleases regulated by EndoG.
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