Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups—Mannich phenols and general bases—that are capable of reactivating OPC‐inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE.     

Optimal cascade hydraulic control for a parallel robot platform by PSO

A new cascade load force control design for a parallel robot platform is proposed. A parameter search for a proposed cascade controller is difficult because there is no methodology to set the parameters and the search space is broad. A parameter search based on particle swarm optimization (PSO) is suggested to effectively search the parameters of the cascade controller. We used a unified mathematical model of a hydraulic actuator of parallel robot platform. These equations are readily applicable to various types of proportional valves, and they unify the cases of critical center, overlapped, and underlapped valves. These unified model equations are useful for nonlinear controller design. Simulation results show the advantages of the proposed optimal tuned cascade controller to solve the formulated tracking problem in relation to the classical proportional–integral (PI) controller.     

Effect of commercial or depurinized milk on rat liver growth-regulatory kinases,nuclear factor-kappa B,and endonuclease in experimental hyperuricemia: Comparison with allopurinol therapy

Hyperuricemia is a biochemical hallmark of gout, renal urate lithiasis, and inherited purine disorders, and may be a result of enormous ATP breakdown or purine release as a result of cardiovascular disease, hypertension, kidney disease, eclampsia, obesity, metabolic syndrome, psoriasis, tumor lysis syndrome, or intense physical training. The beneficial role of dairy products on hyperuricemia management and prevention is well documented in the literature. The primary aim of our experimental study was to examine the effect of milk dietary regimen (commercial 1.5% fat UHT milk or patented depurinized milk) compared with allopurinol therapy on experimental hyperuricemia induced by oxonic acid in rats. Principal component analysis was applied on a data set consisting of 11 variables for 8 different experimental groups. Among the 11 parameters measured (plasma uric acid and the liver parameters NFκB-p65, Akt kinase/phospho-Akt kinase, ERK kinase/phospho-ERK kinase, IRAK kinase/phospho IRAK kinase, p38/phospho-p38, and DNase), Akt/phospho Akt and ERK/phospho-ERK signaling were extracted as the most discriminating. We also compared the content of various potentially toxic compounds (sulfur compounds, ketones, aldehydes, alcohols, esters, carboxylic acids, and phthalates) in untreated commercial milk and depurinized milk. Of all the compounds investigated in this study that were observed in commercial milk (24 volatile organic compounds and 4 phthalates), 6 volatile organic compounds were not detected in depurinized milk. For almost all of the other compounds, significant decreases in concentration were observed in depurinized milk compared with commercial milk. In conclusion, a depurinized milk diet may be recommended in nutritional treatment of primary and secondary hyperuricemia to avoid uric acid and other volatile, potentially toxic compounds that may slow down liver regeneration and may induce chronic liver diseases.     

Influence of osmotic concentration,continuous high frequency ultrasound and dehydration on antioxidants,colour and chemical properties of rabbiteye blueberries

Rabbiteye blueberries (Vaccinium ashei Reade) were osmoconcentrated in a sucrose solution for 12 h, and for 3 h, with and without high frequency ultrasound (CHFU). Treated and untreated samples were air-dehydrated (70 °C, 10 h). Osmoconcentration decreased titratable acidity and induced a high loss of anthocyanins and phenolics. Approximately 60% of anthocyanins and phenolics were lost during osmoconcentration for 12 h. Air-dehydration further decreased anthocyanins and phenolics, with a higher negative influence on anthocyanins. Dehydration, after osmotic concentration, produced the largest colour differences in comparison to the control. High frequency ultrasound had a negative influence on anthocyanins and phenolics. Antioxidant activity was lowest in osmoconcentrated and dehydrated berries. Combination of high temperature, high sugar concentration and oxygen availability had the largest negative influence on colour and antioxidant properties (anthocyanins and phenolics) of dehydrated rabbiteye blueberries.     

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products,cardiovascular markers,and bone marrow CD34 stem cell potential in rat experimental hyperuricemia

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34⁺, CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34⁺ stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34⁺. Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function.     

Adaptive Input Design for Identification of Output Error Model with Constrained Output

Optimal input design for system identification is an area of intensive modern research. This paper considers the identification of output error (OE) model, for the case of constrained output variance. The constraint plays a very important role in the process industry, in the reduction of degradation of product quality. In this paper, it is shown, in the form of a theorem, that the optimal input signal, with constrained output, is achieved by a minimum variance controller together with a stochastic reference. The key problem is that the optimal input depends on the system parameters to be identified. In order to overcome this problem, a two-stage adaptive procedure is proposed: obtaining an initial model using PRBS as input signal; application of adaptive minimum variance controller together with the stochastic variable reference, in order to generate input signals for system identification. Theoretical results are illustrated by simulations.     

Characterization of novel varistor+inductor integrated passive devices

This letter describes the design, modeling, simulation, and fabrication of novel integrated passive devices (IPDs). These IPDs, comprising of a cofired multilayered varistor and inductor, have been developed in the ceramic coprocessing technology. The equivalent model of the new structures is presented, suitable for design and circuit simulations. The fabrication method, new design of structures and patented materials of these devices lead to improved characteristics suitable for application in high-frequency suppressors. The IPDs were tested in the frequency range of 1 MHz-3 GHz using an Agilent 4287A RF LCR meter. The measurements confirm the validity of the proposed model.     

Development of a rotating ring-disc electrode for high temperature studies in cryolite-based melts

A compact rotating ring-disc electrode incorporating a molybdenum disc, gold ring and boron nitride insulator has been designed, constructed and evaluated in molten cryolite-based electrolytes at temperatures up to 1000°C and rotation rates between 0 and 2000 rpm. The electrode design is extremely versatile and relatively maintenance free, with no visible evidence of melt leakage at the ring-insulator and disc-insulator interfaces. The operating performance of the gold-molybdenum rotating ring-disc electrode was evaluated from collection efficiency measurements based on the dissolution of the disc surface and subsequent detection of soluble species transported to the ring. The observed collection efficiency was less than the theoretical value determined from the geometry of the electrode, primarily because of noncoplanarity of the electrode surface at the working temperature. The results confirm that the electrode should be useful for mechanistic studies in high temperature molten fluoride electrolytes.     

Identification of static load characteristics based on measurements in medium-voltage distribution network

The authors deal with static load (SL) characteristics (P-V and Q-V characteristics) of a medium-voltage distribution network derived from field measurements. The experiments have been performed by changing the tap position of an on-load tap-changing transformer in different seasons, different week days and day periods. P-V and Q-V load characteristics are divided into two classes, transient and steady-state characteristics. The differences between them are discussed and quantified. Both classes are mathematically described by polynomial, linear and exponential SL models. Model parameters are obtained by curve fitting using a least square method. The adequacy of developed load models is critically assessed and discussed. All the static characteristics are grouped according to seasons and day periods and are mutually compared. Finally, the parameters of the SL models for residential load without electrical heating are suggested for different seasons.