A New Mathematical Model of Functionally Graded Porous Euler-Bernoulli Nanoscaled Beams Taking into Account Some Types of Nonlinearities.

A new mathematical model of flexible physically (FN), geometrically (GN), and simultaneously physically and geometrically (PGN) nonlinear porous functionally graded (PFG) Euler-Bernoulli beams was developed using a modified couple stress theory. The ceramic phase of the functionally material was considered as an elastic material. The metal phase was considered as a physically non-linear material dependent on coordinates, time, and stress-strain state, which gave the opportunity to apply the deformation theory of plasticity.

Stability Improvement of Flexible Shallow Shells Using Neutron Radiation.

Microelectromechanical systems (MEMS) are increasingly playing a significant role in the aviation industry and space exploration. Moreover, there is a need to study the neutron radiation effect on the MEMS structural members and the MEMS devices reliability in general. Experiments with MEMS structural members showed changes in their operation after exposure to neutron radiation.

Decreasing Shear Stresses of the Solder Joints for Mechanical and Thermal Loads by Topological Optimization.

A methodology for obtaining the optimal structure and distribution for the gradient properties of a material in order to reduce the stress level in a soldered joint was constructed. The developed methodology was based on a combination of topological optimization methods (the moving asymptotes method) and the finite elements method; it was first implemented to solve problems of optimizing soldered joints. Using the proposed methodology, a number of problems were solved, allowing one to obtain optimal structural characteristics, in which a decrease in stress is revealed.

EEG Analysis in Structural Focal Epilepsy Using the Methods of Nonlinear Dynamics (Lyapunov Exponents, Lempel-Ziv Complexity, and Multiscale Entropy).

This paper analyzes a case with the patient having focal structural epilepsy by processing electroencephalogram (EEG) fragments containing the "sharp wave" pattern of brain activity. EEG signals were recorded using 21 channels. Based on the fact that EEG signals are time series, an approach has been developed for their analysis using nonlinear dynamics tools: calculating the Lyapunov exponent's spectrum, multiscale entropy, and Lempel-Ziv complexity.

Quantifying Chaos by Various Computational Methods. Part 1: Simple Systems.

The aim of the paper was to analyze the given nonlinear problem by different methods of computation of the Lyapunov exponents (Wolf method, Rosenstein method, Kantz method, the method based on the modification of a neural network, and the synchronization method) for the classical problems governed by difference and differential equations (Hénon map, hyperchaotic Hénon map, logistic map, Rössler attractor, Lorenz attractor) and with the use of both Fourier spectra and Gauss wavelets. It has been shown that a modification of the neural network method makes it possible to compute a spectrum of Lyapunov exponents, and then to detect a transition of the system regular dynamics into chaos, hyperchaos, and others. The aim of the comparison was to evaluate the considered algorithms, study their convergence, and also identify the most suitable algorithms for specific system types and objectives.

Quantifying Chaos by Various Computational Methods. Part 2: Vibrations of the Bernoulli-Euler Beam Subjected to Periodic and Colored Noise.

In this part of the paper, the theory of nonlinear dynamics of flexible Euler-Bernoulli beams (the kinematic model of the first-order approximation) under transverse harmonic load and colored noise has been proposed. It has been shown that the introduced concept of phase transition allows for further generalization of the problem. The concept has been extended to a so-called noise-induced transition, which is a novel transition type exhibited by nonequilibrium systems embedded in a stochastic fluctuated medium, the properties of which depend on time and are influenced by external noise.

Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents.

This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators.

Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin αIIbβ3.

A series of 2-piperazin-1-yl-quinazolines were synthesized and evaluated for their antiaggregative activity. The synthesized small molecule compounds have potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to αIIbβ3 integrin in a suspension of washed human platelets. The key αIIbβ3 protein-ligand interactions were determined in docking experiments and some correlations have been observed between values of the affinity and docking scores.

Design, Virtual Screening, and Synthesis of Antagonists of αIIbβ3 as Antiplatelet Agents.

This article describes design, virtual screening, synthesis, and biological tests of novel αIIbβ3 antagonists, which inhibit platelet aggregation. Two types of αIIbβ3 antagonists were developed: those binding either closed or open form of the protein. At the first step, available experimental data were used to build QSAR models and ligand- and structure-based pharmacophore models and to select the most appropriate tool for ligand-to-protein docking.

On the iterative methods of linearization, decrease of order and dimension of the Karman-type PDEs.

Iterative methods to achieve a suitable linearization as well as a decrease of the order and dimension of nonlinear partial differential equations of the eighth order into the biharmonic and Poisson-type differential equations with their simultaneous linearization are proposed in this work. Validity and reliability of the obtained results are discussed using computer programs developed by the authors.

Chaotic dynamics of flexible Euler-Bernoulli beams.

Mathematical modeling and analysis of spatio-temporal chaotic dynamics of flexible simple and curved Euler-Bernoulli beams are carried out. The Kármán-type geometric non-linearity is considered. Algorithms reducing partial differential equations which govern the dynamics of studied objects and associated boundary value problems are reduced to the Cauchy problem through both Finite Difference Method with the approximation of O(c(2)) and Finite Element Method.

Co-infections with cytomegalovirus and human herpesvirus type 7 in adult Polish allogeneic haematopoietic stem cell transplant recipients.

Human herpesvirus 7 (HHV-7) is widespread around the world and may also be a possible cofactor for cytomegalovirus (CMV) infection in haematopoietic stem cell transplant (HSCT) recipients. In case of viral diseases where specific treatment is available, real-time PCR assays constitute reliable diagnostic tools enabling timely initiation of appropriate therapy and rapid assessment of the efficacy of antiviral treatment strategies. The presence of CMV and HHV-7 was confirmed by the detection of viral DNA isolated from 1,027 plasma samples.

Synthesis, biological evaluation, X-ray molecular structure and molecular docking studies of RGD mimetics containing 6-amino-2,3-dihydroisoindolin-1-one fragment as ligands of integrin αIIbβ₃.

A series of novel RGD mimetics containing phthalimidine fragment was designed and synthesized. Their antiaggregative activity determined by Born's method was shown to be due to inhibition of fibrinogen binding to αIIbβ₃. Molecular docking of RGD mimetics to αIIbβ₃ receptor showed the key interactions in this complex, and also some correlations have been observed between values of biological activity and docking scores.

RGD mimetics containing phthalimidine fragment as novel ligands of fibrinogen receptor.

The novel RGD mimetics with phthalimidine central fragment were synthesized with the use of 4-piperidine-4-yl-butyric, 4-piperidine-4-yl-benzoic, 4-piperazine-4-yl-benzoic and 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acids as surrogates of Arg motif. The synthesized compounds potently inhibited platelet aggregation in vitro and blocked FITC-Fg binding to α(IIb)β(3) integrin in a suspension of washed human platelets. The key α(IIb)β(3) protein-ligand interactions were determined in docking experiments.

Derivatives of tetrahydroisoquinoline: synthesis and initial evaluation of novel non-peptide antagonists of the alpha(IIb)beta(3)-integrin.

The novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-4-oxobutyric or 5-(1,2,3,4-tetrahydroisoquinoline-7-yl)amino-5-oxopentanoic acids as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.

Derivatives of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid as novel fibrinogen receptor antagonists.

It has been proposed a novel method for obtaining of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid as Arg-mimetic within the framework of search for novel fibrinogen receptor antagonists. New alpha (IIb)beta(3) antagonists were prepared on a base of 1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid. Their high antiaggregatory activities in a human platelet rich plasma and ability to block FITC-Fg binding to alpha (IIb)beta(3) on washed human platelets were estimated.

Novel fibrinogen receptor antagonists--RGDF mimetics, 4-(1,2,3,4-tetrahydro-isoquinoline-7-yl)amino-4-oxo-butyric acid derivatives.

Two novel RGDF mimetics were synthesized with the use of 4-(1,2,3,4-tetrahydro-isoquinoline-7-yl)amino-4-oxo-butyric acid as a new surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alphaIIbbeta3 on washed human platelets.

Derivatives of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids as novel fibrinogen receptor antagonists.

The novel fibrinogen receptor antagonists containing fragments of 7-amino-1,2,3,4-tetrahydroisoquinoline and isophthalic acids were synthesized and successfully tested for their ability to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.

[Synthesis and antiaggregative activity of a new RGDF mimetic].

m-[4-Oxo-4-(piperazin-1-yl)butyrylamino)]benzoyl-D,L-beta-(3,4-methylenedioxyphenyl)-beta-alanine, a new mimetic of the peptide RGDF, was synthesized. This compound inhibited ADP-induced platelet aggregation in human blood plasma enriched with platelets with IC50 3.5 x 10(-8) M.

Novel fibrinogen receptor antagonists. RGDF mimetics, derivatives of 4-(isoindoline-5-yl)amino-4-oxobutyric acid.

The novel RGDF mimetics 9a and 9b were synthesized with the use of 4-(isoindoline-5-yl)amino-4-oxobutyric acid as a surrogate of Arg-Gly motif. The synthesized compounds have demonstrated a high potency to inhibit platelet aggregation in vitro and to block FITC-Fg binding to alpha(IIb)beta(3) on washed human platelets.

Peptidomimetics - antagonists of the fibrinogen receptors: molecular design, structures, properties and therapeutic applications.

The platelet aggregation is a crucial step in a pathophisiology of thromboses, leading to development of cardio-vascular diseases (myocardial infarction, transient ischemic attacks, strokes, etc.). The final step in the aggregation is the binding of fibrinogen to receptor - glycoprotein IIb/IIIa (GP IIb/IIIa) on the surface of activated platelets.

Synthesis and antiaggregatory activity of RGD-peptidomimetics based on 4-oxo-4-(piperazine-1-yl)butyric acid as Arg-mimetic.

A scheme of synthesis of previously obtained RGDF-peptidomimetic-4-oxo-4-(piperazine-1-yl)butyrylglycyl-D,L-beta-phenyl-beta-alanine (I), was simplified. The novel RGDF-peptidomimetic -4-oxo-4-piperazine-1-yl)butyryl-glycyl-L-aspartyl-L-phenylalanine (II) was synthesized with the use of 4-oxo-4-(piperazine-1-yl)butyric acid as arginyl mimetic. The obtained pseudopeptides were able to inhibit both platelet aggregation in human blood and binding of fibrinogen to its receptor.

Synthesis and properties of peptidomimetics--inhibitors of platelet aggregation.

The literature data on effective approaches to the development of the novel peptidomimetics, antagonists of fibrinogen GP IIb/IIIa receptors as potential antithrombotic agents are generalized and systematized in the review. The data obtained by the authors on the synthesis and properties of novel peptidomimetics are reported.