Multiparameter Optimization of Trypanocidal Cruzain Inhibitors With In Vivo Activity and Favorable Pharmacokinetics

Cruzain, the main cysteine protease of Trypanosoma cruzi, plays key roles in all stages of the parasite’s life cycle, including nutrition acquisition, differentiation, evasion of the host immune system, and invasion of host cells. Thus, inhibition of this validated target may lead to the development of novel drugs for the treatment of Chagas disease. In this study, a multiparameter optimization (MPO) approach, molecular modeling, and structure-activity relationships (SARs) were employed for the identification of new benzimidazole derivatives as potent competitive inhibitors of cruzain with trypanocidal activity and suitable pharmacokinetics. Extensive pharmacokinetic studies enabled the identification of metabolically stable and permeable compounds with high selectivity indices. CYP3A4 was found to be involved in the main metabolic pathway, and the identification of metabolic soft spots provided insights into molecular optimization. Compound 28, which showed a promising trade-off between pharmacodynamics and pharmacokinetics, caused no acute toxicity and reduced parasite burden both in vitro and in vivo.

Genetic Decompilation Concept of the Telecommunication Devices Machine Code

Reverse engineering correct source code from a machine code to find and neutralize vulnerabilities is the most pressing problem for the field of telecommunications equipment. The decompilation techniques applicable for this have potentially reached their evolutionary limit. As a result, new concepts are required that can make a quantum leap in problem solving. Proceeding from this, the paper proposes the concept of genetic decompilation, which is a solution to the problem of multiparameter optimization in the form of iterative approximation of instances of the source code to the "original" one which will compile to the given machine code. This concept is tested by conducting a series of experiments with the developed software prototype using a basic example of machine code. The results of the experiments prove the proof of the concept, thereby suggesting new innovative directions for ensuring information security in this subject area.

Multiparameter Optimization Framework of Cyberphysical Systems: A Case Study on Energy Saving of the Automotive Engine

Multiparameter optimization of complex electromechanical systems in a physical space is a challenging task. CPS (Cyberphysical system) technology can speed up the solution of the problem based on data interaction and collaborative optimization of physical space and cyberspace. This paper proposed a general multiparameter optimization framework by combining physical process simulation and clustering genetic algorithm for the CPS application. The utility of this approach is demonstrated in the instance of automobile engine energy-saving in this paper. A 1.8-L turbocharged GDI (gasoline direct injection) engine model was established and calibrated according to the test data and physical entity. A joint simulation program combining CGA (Clustering Genetic Algorithm) with the GDI engine simulation model was set up for the engine multiparameter optimization and performance prediction in cyberspace; then, the influential mechanism of multiple factors on engine energy-saving optimization was analyzed at 2000 RPM (Revolutions Per Minute) working condition. A multiparameter optimization with clustering genetic algorithm was introduced for multiparameter optimization among physical and digital data. The trade-off between fuel efficiency, dynamic performance, and knock risk was discussed. The results demonstrated the effectiveness of the proposed method and that it can contribute to develop a novel automotive engine control strategy in the future.

Food’s Waste Water Biosolid Assessment against Toxic Element Absorbability of Food’s Cropping Soil Plant by Dominance Theory

The blending of the Food’s Waste Water Biosolid (FWWB) fertilizer with Food’s Cropping Soil (FsCS) results the absorption of the toxic macromicroorganisms from FsCS (is known as absorbability index). It is observed that such as blending not only increase the fertility and productivity of FsCS by neutralizing or absorbing the macromicroorganisms but also catering the necessary nutrition to plants. The authors sensed that a few research works are conducted recently in the dimension of evaluating the best FWWB among available FWWBs under O -(objective) FWWB’s parameter models. On potential analysis of published research works, the authors claimed that there is yet no research document, which can evaluate the best FWWB among available FWWBs or assess the best absorbability index of O -(objective) as well as S -(subjective) FWWB’s model corresponding to evaluated FWWBs or alternative points. It is accepted as a first research challenge. On extensive review, the authors determined that published FWWB’s parameter models are simulated by only single or nondynamic multivariable optimization techniques, which is accepted as a second research challenge. To address both research challenges, preliminary, the authors developed and proposed FWWB’s parameter model, consisted of physical, chemical, and biological parameters corresponding to O and S in nature via auditing a real case of FWWB alternative points such as Narendr Rice Mill- P 1 , Liese Mahamaya Rice Mill- P 2 , Vijay Rice Mill- P 3 , Mahim Rice Mill- P 4 , and Dhansingh Rice Mill- P 5 and their characteristics vs. parameters. Next, the authors framed the FWWB parameter model by acquiring O and S information against O -physical, chemical, and S -biological parameters corresponding to FWWB alternative points. To evaluate the results, the authors applied the robust multiparameter optimization “RMPO” (crisp VIKOR “VIseKriterijumska Optimizacija I Kompromisno Resenje” and FMF “Full Multiplicative Form technique with dominance theory”) approach on defuzzified S -data and O -data to evaluate the best FWWB point among available based on absorbability index assessment. The results are described in summary part.

The Shortcomings of the Existing Economic Theory and Their Elimination

Th e paper analyzes the state and management of country’s economics. A tuple of event-driven optimal management as a method of artifi cial intelligence has been developed. Th e characteristics of event-driven quality management of associative and structurally complex systems and processes are given. Th e events and probabilities in the management of economics and the state are considered. A measure of invalidation has been introduced for parameters. Th e method of synthesis of the probability of an event based on expert information is presented. Th e necessity of orthogonalization of the logical function and the transition to the probabilistic function have been substantiated. Th e eff ect of repeated initiating events is considered. One-dimensional optimization of the system on a logical model instead of arithmetic multiparameter optimization is presented. Schemes for managing of development and exit of economics from stagnation are given. Th e tools for event-driven quality management of systems and processes are described. Th e analysis of the shortcomings of the existing economic theory and the possibility of their elimination is carried out.

Analyzing the Thermodynamic Efficiency of Cooling Cycles Depending on the Determinant Thermal and Physical Properties of Operating Media

The goal of this research was to develop the methods used for the analysis of the thermodynamic efficiency of the ordinary single-stage and regenerative cooling cycles depending on the determinant thermal-&-physical properties of cooling agents. The thermodynamic efficiency of the steam –compressive single-stage ordinary and regenerative cycles of cooling machines operating on different cooling agents has been investigated. The dependence was established between the effectiveness value of the use of the regeneration for the cooling cycle and the modified Clausius criterion of the cooling agent. Generalized regressive dependences were obtained for the evaluation of the efficiency of the ordinary and regenerative cycles based on the determinant modified Clausius criterion and these give us an opportunity to establish the fields for the preferential use of the promising cooling agents for regenerative cycles and establish requirements to the properties of cooling agents during their choice. These contribute to the selection of the rational flowchart for the specified thermal and physical characteristics of the cooling agent and for the thermal behavior of the unit operation and form appropriate rational geometric characteristics for the heat exchangers and interconnecting piping. The suggested methods enable the determination of the expected characteristics of the unit and the boundary attainable values of its efficiency in the conditions of the limited information on the thermal-&-physical properties of new (by-way) cooling agents without waiting for the appearance of accurate state diagrams. Analytical equations used for the estimation of the cooling factor depending on the modified Clausius criterion allow us to perform the front-end project computations making use of only absolute values of evaporation and condensation temperatures. The effect of the steam depression, the dryness value and the efficiency factor of the regenerative heat exchanger on the cooling factor of the cycle has been studied. A practical value of the obtained data consists in the opportunity of the objective and operative estimation of the efficiency of the use of the cooling agent for the regenerative and steam compressing cycles of the cooling machine using no multiparameter optimization procedure.

Optimization and Comparison of Two Technologies for the Manufacture of Blades for Flow path HPC Turbine K-330-23.5

The article presents the results of multiparameter optimization of the structural and thermogasdynamic parameters of the flow path of the HPC K-330-23.5, obtained using the developed CAD “Turboagregat”. The found 12 optimal solutions for the flow path of the HPCK-330-23.5 make it possible not only to assess the effect of the design parameters and the number of blades of the HPC stages on the HPC efficiency, but also to carry out a comparative analysis of two technological approaches to manufacturing the rotor blades – with and without trimming the initial edges. Calculations have confirmed the negative effect of increasing the radius of the “tummy” circle on the nature of the flow and on the efficiency of the cascades. In cascades with increased profiles by 9.83 % with a radius of the “tummy” circle, the coefficient of profile losses of the cascade increased by 0.07 % (absolute) in comparison with the original cascade from the original 1MMK-U profiles.