Targeting Mitochondria in Diabetes

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.     

Mathematical model of gentamicin sulfate release from a bioactive textile material as a transdermal system under in vitro conditions

A mathematical model was developed to estimate the release of gentamicin sulfate from a bioactive textile material as a transdermal system for wound dressing. The gentamicin sulfate released from the antibiotic/chitosan hydrogel complexes was measured in vitro by the Franz diffusion cell technique. The diffusive transport of gentamicin sulfate through three connected compartments, that is, chitosan hydrogel, membrane, and solution, was considered by the formulation of a model based on Fick's second law. Initially, the total amount of gentamicin sulfate was placed within an already swollen chitosan hydrogel. The value of the diffusivity coefficient of the drug through the chitosan hydrogel was calculated for every initial amount of the active substance. For the initial concentration of gentamicin sulfate, which was lower than 2.81 × 10⁴ μg/mL, the diffusion coefficient was approximately constant. A higher amount of gentamicin sulfate in the hydrogel reduced its own transport as a consequence of an increase in the intensity of the interaction field between the molecules of gentamicin sulfate. The model provides the possibility of optimizing the process of drug release by ensuring a compromise between a higher value of the diffusivity coefficient and a desirable amount of gentamicin sulfate and a constant concentration within the solution over 48 h. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Hydrolysis of pumpkin oil cake protein isolate and free radical scavenging activity of hydrolysates: Influence of temperature,enzyme/substrate ratio and time

The effect of hydrolysis parameters (temperature, initial enzyme/substrate ratio and time) on the hydrolysis of pumpkin oil cake protein isolate (PuOC PI) with acid protease from Aspergillus niger and the antioxidant potency of the obtained hydrolysates were studied by response surface methodology (RSM). The hydrolysis progress, measured by the degree of hydrolysis (DH), was described by a second-order polynomial model (R² = 0.77) and the conditions for optimum DH (42.94%) were found at temperature of 40 °C, enzyme/substrate ratio (E/S) 4.38 HUT/mg of substrate proteins and 85 min. The antiradical activity (AA) of the PuOC PI hydrolysates was examined by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay; all hydrolysates showed a concentration dependent scavenging activity against DPPH radicals. The AA of hydrolysates was influenced by process parameters and was presented also by a second-order polynomial model (R² = 0.7). The conditions to achieve the highest DH did not result hydrolysates with the optimum AA; the highest AA ranged from 34% to 40% and were found in hydrolysates obtained at 50 °C.     

Influence of Rare-Earth Dopants on Barium Titanate Ceramics Microstructure and Corresponding Electrical Properties

In this article, ytterbium and erbium oxides are used as doping materials for barium titanate (BaTiO₃) materials. The amphoteric behavior of these rare-earth ions leads to the increase of dielectric permittivity and decrease of dielectric losses. BaTiO₃ ceramics doped with 0.01–0.5 wt% of Yb₂O₃ and Er₂O₃ were prepared by conventional solid-state procedure and sintered at 1320°C for 4 h. In BaTiO₃ doped with a low content of rare-earth ions (0.01 wt%) the grain size ranged between 10 and 25 μm. With the higher dopant concentration of 0.5 wt%, the abnormal grain growth is inhibited and the grain size ranged between 2 and 10 μm. The measurements of capacitance and dielectric losses as a function of frequency and temperature have been carried out in order to correlate the microstructure and dielectric properties of doped BaTiO₃ ceramics. The temperature dependence of the dielectric constant as a function of dopant amount has been investigated.     

Improvement of the stoichiometric network analysis for determination of instability conditions of complex nonlinear reaction systems

Stoichiometric network analysis (SNA), a known method for analyzing complex reaction systems including biochemical ones, is improved and applied to a nonlinear process studied far from equilibrium in a continuously fed, well stirred tank reactor (CSTR). A particular attention is focused on the determination of the narrow range of the control parameter values where the main steady state is unstable and where different dynamic states can be simulated numerically. The instability region, the most important feature of nonlinear reaction systems, is calculated as a function of the SNA parameters (current rates and reciprocal concentrations of intermediate species in the steady state) and simplified by retaining only the dominant terms. Since the number of the current rates is usually larger than the number of linearly independent equations to be used for their calculation, it is shown here that the current rates can be replaced with a smaller number of reaction rates at the steady state. These rates are related to the experimental data in a simple manner. The instability condition is also written as a function of dimensionless parameters derived from the SNA. This general approach is applied to a model of the Bray–Liebhafsky (BL) reaction having seven reactions without direct autocatalysis or autoinhibition, studied under CSTR conditions. Since the model has six intermediate species, it would be very difficult to analyze its instability condition by the conventional procedure, where a sixth order characteristic equation would have to be solved. On the other hand, the instability condition, obtained easily by the improved SNA, locates correctly the oscillatory region using numerical integration. Other dynamic states found earlier with a larger model of the BL reaction, such as mixed-mode oscillations, period doubling and chaos, are also obtained within the theoretically predicted oscillatory region. Thus, besides the general advantages of the improved stoichiometric network analysis as a method appropriate for the examination of complex nonlinear reactions, we show that the various mentioned dynamic states can be obtained by a very simple variant of the model of the BL reaction realized under CSTR conditions.     

Physical and microscopic studies of flour–water systems

Two flour–water systems were prepared under different conditions. A mixed flour–water system (dough) was prepared by mixing and kneading, and an unmixed (Hydrated, Unmixed Flour=HUF system) flour–water system without mixing and kneading. For preparation of the systems wheat flours of different qualities were used. Characterisation of the systems was done by rheological and microscopic analyses. Rheological measurements were performed at small deformation in dynamic oscillating mode, as well as at large deformation by uniaxial extension. The dough, the HUF system and the gluten from them were also investigated by microscopic technique.The mixed and unmixed systems showed differences in structure causing different physical properties. At small deformations (dynamic oscillating measurements) as well as at large ones (uniaxial extension measurements) HUF systems were firmer than doughs having a higher resistance in uniaxial extension measurements and higher elasticity at the beginning of dynamic measurements. Differences in structure of dehydrated systems were also found by microscopic investigations.Presented in part at 51. Tagung für Getreidechemie, 2000, Detmold, Germany     

Data dissemination in wireless broadcast channels: Network coding versus cooperation

Network coding and cooperative diversity have each extensively been explored in the literature as a means to substantially improve the performance of wireless networks. Yet, little work has been conducted to compare their performance under a common framework. Our goal in this paper is to fill in this gap. Specifically, we consider a single-hop wireless network consisting of a base station and N receivers. We perform an asymptotic analysis, as N → ∞, of the expected delay associated with the broadcasting of a file consisting of K packets. We show that if K is fixed, cooperation outperforms network coding, in the sense that the expected delay is proportional to K (and thus within a constant factor of the optimal delay) in the former case while it grows logarithmically with N in the latter case. On the other hand, if K grows with N at a rate at least as fast as (logN)^r, for r ≫ 1, then we show that the average delay of network coding is also proportional to K and lower than the average delay of cooperation if the packet error probability is smaller than 0.36. Our analytical findings are validated through extensive numerical simulations.     

An adaptive e-questionnaire for measuring user perceived portal quality

In this paper we describe an adaptive e-questionnaire system that can be used for measuring user feedback concerning the quality of portals and e-services. The proposed system applies three axes of adaptation: based on real-time feedback from users through questionnaires, based on problems encountered by the user and based on metadata of the pages visited by the user. The system is based on a model for adaptive quality measurement (MAQM), which comprises different ontologies including concepts regarding the quality of portal and e-services, the questions and questionnaires, the portal characteristics (e.g. page types), the user behavior and the user-encountered problems. The results of evaluating the system’s usefulness in an e-government portal are indicative of the value added of our approach. The user experience associated with the quality assessment process is improved and the portal provider gets better feedback in terms of quantity and quality.     

Methods for true energy-performance optimization

This paper presents methods for efficient energy-performance optimization at the circuit and micro-architectural levels. The optimal balance between energy and performance is achieved when the sensitivity of energy to a change in performance is equal for all the design variables. The sensitivity-based optimizations minimize energy subject to a delay constraint. Energy savings of about 65% can be achieved without delay penalty with equalization of sensitivities to sizing, supply, and threshold voltage in a 64-bit adder, compared to the reference design sized for minimum delay. Circuit optimization is effective only in the region of about /spl plusmn/30% around the reference delay; outside of this region the optimization becomes too costly either in terms of energy or delay. Using optimal energy-delay tradeoffs from the circuit level and introducing more degrees of freedom, the optimization is hierarchically extended to higher abstraction layers. We focus on the micro-architectural optimization and demonstrate that the scope of energy-efficient optimization can be extended by the choice of circuit topology or the level of parallelism. In a 64-bit ALU example, parallelism of five provides a three-fold performance increase, while requiring the same energy as the reference design. Parallel or time-multiplexed solutions significantly affect the area of their respective designs, so the overall design cost is minimized when optimal energy-area tradeoff is achieved.