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排序方式: 共有86条查询结果,搜索用时 27 毫秒
1.
Dawid Polak Marcin Talar Nina Wolska Dagmara W. Wojkowska Kamil Karolczak Karol Kramkowski Tomasz A. Bonda Cezary Watala Tomasz Przygodzki 《International journal of molecular sciences》2021,22(6)
Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y12 could serve as components of dual anti-platelet therapy. We have found that a selective A2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y12 inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146. 相似文献
2.
Cezary Graczykowski Tomasz Lewiński 《Structural and Multidisciplinary Optimization》2010,42(6):869-877
The paper delivers the benchmark results for the Michell cantilevers constructed within a half strip, for selected values
of the σ
T
/σ
C
ratio, σ
T
, σ
C
being the admissible stresses in tension and compression, respectively. 相似文献
3.
4.
5.
Yuki Chikahiro Ichiro Ario Piotr Pawlowski Cezary Graczykowski Jan Holnicki‐Szulc 《Computer-Aided Civil and Infrastructure Engineering》2019,34(6):523-538
Scissors mechanisms are commonly used in safety engineering during the construction of temporary structures, owing to their inherent advantages of foldability, transformability, and reusability. We effectively utilized these scissors mechanism features to develop a lightweight, deployable emergency Mobile Bridge (MB) based on optimization, and control of the folding structure. Here, we discuss the problems of optimal reinforcement layout for the MB by formulating and solving three optimization problems, namely: (a) the load capacity maximization problem, (b) the weight minimization problem, and (c) coupling the load capacity maximization problem and the weight minimization problem. The potential benefits resulting from the application of reinforcement were evaluated using a combination of finite element analysis and an optimization algorithm based on the differential evolution method. The results demonstrate the significant positive influence of the additional reinforcing members. In particular, the limit load was increased by over 10 times, while the weight was decreased to approximately half. The proposed methodology enabled the development of a substantially improved version of the MB characterized by a higher load capacity and lower weight in comparison to the initial bridge design. 相似文献
6.
Czaplewski C Oldziej S Liwo A Scheraga HA 《Protein engineering, design & selection : PEDS》2004,17(1):29-36
The presence of disulfide bonds is essential for maintaining the structure and function of many proteins. The disulfide bonds are usually formed dynamically during folding. This process is not accounted for in present algorithms for protein-structure prediction, which either deduce the possible positions of disulfide bonds only after the structure is formed or assume fixed disulfide bonds during the course of simulated folding. In this work, the conformational space annealing (CSA) method and the UNRES united-residue force field were extended to treat dynamic formation of disulfide bonds. A harmonic potential is imposed on the distance between disulfide-bonded cysteine side-chain centroids to describe the energetics of bond distortion and an energy gain of 5.5 kcal/mol is added for disulfide-bond formation. Formation, breaking and rearrangement of disulfide bonds are included in the CSA search by introducing appropriate operations; the search can also be carried out with a fixed disulfide-bond arrangement. The algorithm was applied to four proteins: 1EI0 (alpha), 1NKL (alpha), 1L1I (beta-helix) and 1ED0 (alpha + beta). For 1EI0, a low-energy structure with correct fold was obtained both in the runs without and with disulfide bonds; however, it was obtained as the lowest in energy only with the native disulfide-bond arrangement. For the other proteins studied, structures with the correct fold were obtained as the lowest (1NKL and 1L1I) or low-energy structures (1ED0) only in runs with disulfide bonds, although the final disulfide-bond arrangement was non-native. The results demonstrate that, by including the possibility of formation of disulfide bonds, the predictive power of the UNRES force field is enhanced, even though the disulfide-bond potential introduced here rarely produces disulfide bonds in native positions. To the best of our knowledge, this is the first algorithm for energy-based prediction of the structure of disulfide-bonded proteins without any assumption as to the positions of native disulfides or human intervention. Directions for improving the potentials and the search method are suggested. 相似文献
7.
Reinhard König Cezary Sielużycki Piotr J. Durka 《Journal of Low Temperature Physics》2007,146(5-6):697-718
Low-temperature superconductivity plays an important role in some specific biomedical applications, and, in particular, in
non-invasive imaging methods of human brain activity. Superconducting magnets are indispensable for functional magnetic resonance
imaging (fMRI) which allows functional imaging of the brain with high spatial but poor temporal resolution. Superconducting
quantum interference devices (SQUIDs) are the most sensitive magnetic field detectors. Up to a few hundreds of SQUIDs are
nowdays used in modern whole-head magnetoencephalography (MEG) systems. They allow tracking brain activation with a superior
temporal resolution of milliseconds, which is a quintessential condition for the monitoring of brain dynamics and the understanding
of information processing in the human brain. We introduce the prerequisites of MEG data acquisition and briefly review two
established methods of biomagnetic signal processing: The concept of signal averaging, and the subsequent source identification
as a solution of the biomagnetic inverse problem. Beside these standard techniques, we discuss advanced methods for signal
processing in MEG, which take into account the frequency content of the recorded signal. We briefly refer to the prospects
of Fourier analysis and wavelet transform in MEG data analysis, and suggest matching pursuit as a promising tool for signal
decomposition and reconstruction with high resolution in time-frequency plane. 相似文献
8.
9.
Cezary Czaplewski Adam Liwo Jaros?aw Pillardy Stanis?aw O?dziej Harold A. Scheraga 《Polymer》2004,45(2):677-686
Successful application of physics-based protein-structure prediction methods depends on sophisticated computational approaches to global optimization of the conformational energy of a polypeptide chain. One of the most effective procedures for the global optimization of protein structures appears to be the Conformational Space Annealing (CSA) method. CSA is a hybrid method which combines genetic algorithms, essential aspects of the build-up method and a local gradient-based minimization. CSA evolves the population of conformations through genetic operators (mutations, i.e. perturbations of selected geometric parameters, and crossovers, i.e. exchange of selected subsets of geometric parameters between conformations) to a final population optimizing their conformational energy. Implementation of the CSA method with the united-residue force field (UNRES, in which each amino-acid residue is represented by two interaction sites, namely the united peptide group and the united side-chain) was enhanced by introducing new crossover operations consisting of (i) copying β-hairpins, (ii) copying remote strand pairs forming non-local β-sheets, and (iii) copying α-helical segments. A mutation operation, which shifts the position of a β-turn, was also introduced. The new operations promote β-structure, and are essential for searching the conformational space of proteins containing both α- and β-structure; without these operations, excessive preference of α-helical structures is obtained, even though these structures are high in energy. Parallelization of the CSA method has also been enhanced by removing most of the synchronization steps; the improved algorithm scales almost linearly up to 1,000 processors with over 75% average performance. 相似文献
10.
Rubber elements, which usually form a major part of different isolators of vibrations, are generally easily swelled by oils, greases, or fuels. This leads to meaningful changes of their mechanical characteristics and shortening of durability of rubber components in service. The influence of the semisynthetic motor oil on mechanical and, particularly, dynamic properties of swelled vulcanizates of the polar diene rubber, chloroprene (CR) and acrylonitrile‐butadiene (NBR), is estimated in this article. These elastomers, as is widely known, are resistant to the mineral oils absorption. However, our investigations showed that even a small degree of swelling of the vulcanizates causes decrease of their mechanical properties and considerable changes of the dynamic characteristics of the samples. The obtained results have shown the need to take into account the environment in which isolators of vibrations and dampers have worked, while designing the suitable composition of rubber compounds. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006 相似文献