Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

High areal capacitance of FeOOH-carbon nanotube negative electrodes for asymmetric supercapacitors

The relatively low capacitance of negative electrodes, as compared to the capacitance of advanced positive electrodes, poses a serious problem, since this limits the development of asymmetric supercapacitor (SC) devices with a large voltage window and enhanced power-energy characteristics. We fabricate negative SC electrodes with a high capacitance that match the capacitance of advanced positive electrodes at similar active mass loadings, as high as 37?mg?cm^?2. Cyclic voltammetry, impedance spectroscopy, galvanostatic charge-discharge data and the power-energy characteristics of the asymmetric SC device exhibit good electrochemical performance for a voltage window of 1.6?V. Our approach involves the development and application of particle extraction through liquid-liquid interface (PELLI) methods, new extraction mechanisms and efficient extractors to synthesize α-FeOOH and β-FeOOH electrode materials. The use of PELLI allows agglomerate-free processing of powders, which facilitates their efficient mixing with multiwalled carbon nanotubes (MWCNT) and allows improved electrolyte access to the particle surface. Experiments to determine the properties of FeOOH-MWCNT composites provided insight into the influence of the electrode material and the structure of extractor molecules on the composite properties. The highest capacitance of 5.86?F?cm^?2 for negative electrodes and low impedance were achieved using α-FeOOH-MWCNT composites and a 16-phosphonohexadecanoic acid (PHDA) extractor. This extractor allows adsorption on particles, not only at the liquid-liquid interface, but also in the bulk aqueous phase and can potentially be used as a capping agent for particle synthesis and as an extractor in the PELLI method.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

Deterministic safety study of advanced molten salt nuclear systems for prospective nuclear power

The inter-comparative analysis of the deterministic safety potential of innovative molten salt systems with critical and sub-critical cores is presented for both fast and thermal neutron spectra. The analysis includes two aspects: the choice of an initial level of sub-criticality and the study of multiple unprotected transients which have been simulated on the basis of one-point kinetics and two-point thermo-hydraulic schemes considering realistic feedback effects. Our preliminary results show that even small levels of sub-criticality (2–3 dollars) of cores can improve their safety characteristics significantly.     

Image processing using cellular neural networks based on multi-valued and universal binary neurons

Multi-valued and universal binary neurons (MVN and UBN) are the neural processing elements with the complex-valued weights and high functionality. It is possible to implement an arbitrary mapping described by partially defined multiple-valued function on the single MVN. An arbitrary mapping described by partially defined or fully defined Boolean function, which can be non-threshold, may be implemented on the single UBN. The quickly converging learning algorithms exist for both types of neurons. Such features of the MVN and UBN may be used for solving the different problems. One of the most successful applications of the MVN and UBN is their usage as basic neurons in the Cellular Neural Networks (CNN). It opens the new effective opportunities in nonlinear image filtering and its applications to noise reduction, edge detection and solving of the super resolution problem. A number of experimental results are presented to illustrate the performance of the proposed algorithms.An erratum to this article can be found at     

Control of discrete time nonlinear systems with a time-varying structure

In this paper, we present a control methodology for a class of discrete time nonlinear systems that depend on a possibly exogenous scheduling variable. This class of systems consists of an interpolation of nonlinear dynamic equations in strict feedback form, and it may represent systems with a time-varying nonlinear structure. Moreover, this class of systems is able to represent some cases of gain scheduling control, Takagi-Sugeno fuzzy systems, as well as input-output realizations of nonlinear systems which are approximated via localized linearizations. We present two control theorems, one using what we call a “global” approach (akin to traditional backstepping), and a “local” approach, our main result, where backstepping is again used but the control law is an interpolation of local control terms. An aircraft wing rock regulation problem with varying angle of attack is used to illustrate and compare the two approaches.