32 research outputs found
Information technologies and human factor in civil aviation
The article makes the philosophical analysis of correlation of information and
communication systems, modern means of communications and navigation, and the role of
the human factor in increasing the safety of aircraft flying in civil aviatio
Lipoxygenases and Poly(ADP-Ribose) Polymerase in Amyloid Beta Cytotoxicity
The 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the amyloid β (Aβ) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human Aβ precursor protein. Different levels of Aβ secretion and free radicals formation characterize these cells. The results demonstrated a relationship between the Aβ levels and LOX protein expression and activity. High Aβ concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-κB into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. We suggested that AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70–80% of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding non-treated cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in Aβ toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies
HNO Binding in a Heme Protein: Structures, Spectroscopic Properties, and Stabilities
HNO can interact with numerous heme proteins, but atomic level structures are largely unknown. In this work, various structural models for the first stable HNO heme protein complex, MbHNO (Mb, myoglobin), were examined by quantum chemical calculations. This investigation led to the discovery of two novel structural models that can excellently reproduce numerous experimental spectroscopic properties. They are also the first atomic level structures that can account for the experimentally observed high stabilities. These two models involve two distal His conformations as reported previously for MbCNR and MbNO. However, a unique dual hydrogen bonding feature of the HNO binding was not reported before in heme protein complexes with other small molecules such as CO, NO, and O2. These results shall facilitate investigations of HNO bindings in other heme proteins
Using Shifts in Amino Acid Frequency and Substitution Rate to Identify Latent Structural Characters in Base-Excision Repair Enzymes
Protein evolution includes the birth and death of structural motifs. For example, a zinc finger or a salt bridge may be present in some, but not all, members of a protein family. We propose that such transitions are manifest in sequence phylogenies as concerted shifts in substitution rates of amino acids that are neighbors in a representative structure. First, we identified rate shifts in a quartet from the Fpg/Nei family of base excision repair enzymes using a method developed by Xun Gu and coworkers. We found the shifts to be spatially correlated, more precisely, associated with a flexible loop involved in bacterial Fpg substrate specificity. Consistent with our result, sequences and structures provide convincing evidence that this loop plays a very different role in other family members. Second, then, we developed a method for identifying latent protein structural characters (LSC) given a set of homologous sequences based on Gu's method and proximity in a high-resolution structure. Third, we identified LSC and assigned states of LSC to clades within the Fpg/Nei family of base excision repair enzymes. We describe seven LSC; an accompanying Proteopedia page (http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family) describes these in greater detail and facilitates 3D viewing. The LSC we found provided a surprisingly complete picture of the interaction of the protein with the DNA capturing familiar examples, such as a Zn finger, as well as more subtle interactions. Their preponderance is consistent with an important role as phylogenetic characters. Phylogenetic inference based on LSC provided convincing evidence of independent losses of Zn fingers. Structural motifs may serve as important phylogenetic characters and modeling transitions involving structural motifs may provide a much deeper understanding of protein evolution
Intellectual variation by penalty coefficients in the algorithm in constructing the contour of the enclosing structure of the heat network in the environment of the building CAD
The construction of a contour in the CAD of
enclosing structures (ES) is one of the primary tasks at the
stage of visualization of design procedures. Under the contour in
this case we mean a closed polygon with the maximum possible
coordinates for placement. The contour forms a field for the
placement of elements and tracing, so the high-quality design
of its boundaries allows better performance of these operations.
In the CAD visualization subsystem OK, the contour is built on
the basis of analysis of fuzzy information, by selecting penalty
coefficients. The intellectual variation of penalties in constructing
a contour allows us to introduce additional restrictions on its
appearance and avoid problems of typical trace algorithms, such
as: a large number of angles in the construction, non-optimal
character of the problem zones, and others
Role of lysine-57 in the catalytic activities of Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg protein).
The Escherichia coli Fpg protein is involved in the repair of oxidized residues. We examined, by targeted mutagenesis, the effect of the conserved lysine residue at position 57 upon the various catalytic activities of the Fpg protein. Mutant Fpg protein with Lys-57-->Gly (K57G) had dramatically reduced DNA glycosylase activity for the excision of 7,8-dihydro-8-oxo-guanine (8-oxoG). While wild type Fpg protein cleaved 8-oxoG/C DNA with a specificity constant ( k cat/ K M) of 0.11/(nM@min), K57G cleaved the same DNA 55-fold less efficiently. FpgK57G was poorly effective in the formation of Schiff base complex with 8-oxoG/C DNA. The efficiency in the binding of 8-oxoG/C DNA duplex for K57G mutant was decreased 16-fold. The substitution of Lys-57 for another basic amino acid Arg (K57R) had a slight effect on the 8-oxoG-DNA glycosylase activity and Schiff base formation. The DNA glycosylase activities of FpgK57G and FpgK57R using 2,6-diamino-4-hydroxy-5N-methylformamidopyrimidine residues as substrate were comparable to that of wild type Fpg. In vivo, the mutant K57G, in contrast to the mutant K57R and wild type Fpg, only partially restored the ability to prevent spontaneously induced transitions G/C-->T/A in E.coli BH990 ( fpg mutY ) cells. These results suggest an important role for Lys-57 in the 8-oxoG-DNA glycosylase activity of the Fpg protein in vitro and in vivo
Внедрение интеллектуального прогнозирования как компонента технологии визуализации тепловых потоков
The introduction of elements of forecasting, as a
part of computer-aided design systems, walling (CAD PD), to
avoid problems of incorrect determination of the temperature
in the design. At the design stage of the building will allow the
most accurate prediction to choose thermal units and heaters
to maintain optimal indoor climate, as well as improve energy
efficiency of thermal points.
Внедрение элементов прогнозирования, в составе
средств систем автоматизированного проектирования
ограждающих конструкций (САПР ОК), позволит избежать проблемы некорректного определения температуры в конструкции. На стадии проектирования здания
прогнозирование позволит наиболее точно подобрать
тепловые узлы и нагреватели для поддержания оптимальных климатических условий в помещении, а также
повысить энергоэффективность работы тепловых пунктов
Data processing algorithms in adaptive reconfigurable module protecting desighs CAD for rendering a profile of heat flow
В работе рассмотрены основные алгоритмы работы модуля визуализации контура тепловых потоков с
использованием нечеткой логики. Описано применение матриц нечетких решений и введение базы знаний на
основе фреймовой структуры. Приведены основные этапы функционирования алгоритмов и их преимущества.The basic algorithms visualization module circuit heat
flows using fuzzy logic. The application of fuzzy
matrices making and administering the database based
on frame structure. The main steps of operation of the
algorithms and their advantages