Mechanistic Analysis of Drug Release from Theophylline Pellets Coated by Films Containing Pectin,Chitosan and Eudragit® RS

The objective of this study was to obtain detailed information on the mechanism of drug release from mixed-film of pectin-chitosan/Eudragit® RS. Pellets (710–840 μm in diameter) containing 60% theophylline and 40% microcrystalline cellulose were prepared by extrusion-spheronization method. Eudragit® L100-55 enteric coating capsules included film-coated pellets of theophylline in theoretical coating weight gains of 10, 15, and 20%, with pectin-chitosan complex contents of 5, 10, 15, and 20% for each level of weight gain were prepared and subjected to in vitro drug release. Drug release from this system showed a bimodal release profile characteristic with the drug release enhancement, being triggered (burst release) in the colonic medium. The reason for burst drug release may be due to the enzymatic degradation of pectin via pectinolytic enzymes in the simulated colonic medium. The mechanism of drug release from each formulation was evaluated in the terms of zero-order, first-order, Higuchi and Korsmeyer-Peppas models. It was observed that none of the enteric coating capsules showed any drug release in the simulated gastric medium (phase I). The analysis of release profiles showed that zero-order kinetics was found as the better fitting model for all formulations in the simulated small intestine (phase II) and it could be due to the pectin-chitosan swelling and subsequent formation of aqueous channels. In the colonic medium (phase III), due to degradation of pectin and its leaching from the mixed-film, there was a modification in drug release kinetics from swelling-controlled at phase II to anomalous at phase III. It also was found that both zero-order and Higuchi models contributed in colonic drug release from most of the formulations.     

Comparative evaluation of biocompatibility of dense nanostructured and microstructured Hydroxyapatite/Titania composites

This work deals with the biocompatibility of dense nano- and micro-structured Hydroxyapatite/Titania composites prepared by two step and conventional sintering, respectively. By application of two step sintering, it was shown that the final grain size of HA–15 wt.%TiO₂ is maintained lower than 100 nm while by the application of conventional sintering it reaches higher than 100 nm. Biocompatibility of the dense bulks was evaluated by cell attachment and proliferation experiments. Cell morphology, and viability on each nano- and micro-structured Hydroxyapatite/Titania composites were examined at different time points. The nanostructured HA/Titania dense bulk exhibited higher cell viability than a microstructured one. In addition, the effects of ionic products from nano- and micro-structured bulk dissolution on osteoblasts were studied. The MTT test confirmed that the products from nanostructured HA/Titania dense bulk significantly promoted osteoblast proliferation within a certain concentration range.     

Plastic relaxation of the internal stress induced by twinning

The back stress induced in a twin by the surrounding matrix is analysed using a simple two-dimensional finite element model of an elastic elliptical inclusion in a plastic medium. The influence of the ellipse aspect ratio, the matrix yield stress and the external loading on the internal shear stress are investigated. Comparison is made between isotropic and anisotropic yield criteria. It is seen that von Mises plasticity in the matrix (due to glide) leads to complete relaxation of the twin back stress. The closer the applied stress is to the stress required for macroscopic yielding of the matrix, the greater the relaxation of the back stress. To simulate the role of soft shear directions in the matrix, as seen for the case of easy basal slip in hexagonal close-packed metals, Hill’s anisotropic yield surface was employed. These simulations show relaxation of the back stress that is independent of the level of the applied stress. Comparison between simulations and experiments performed on a magnesium alloy reveals higher levels of relaxation in practice. This is possibly due to (i) further twinning as a relaxation mechanism and (ii) the occurrence of neighbouring grains ideally oriented for relaxation. Analytical expressions are developed to capture the trends seen in the simulation. A correction to bring these into line with experiment is proposed as a tentative means of applying the present findings in an analytical framework.     

Study of bipolar pulsed nanocrystalline plasma electrolytic carbonitriding on nanostructure of compound layer for CP-Ti

Surface hardening of commercially pure titanium using bipolar pulsed nanocrystalline plasma electrolytic carbonitriding has been studied in this investigation. The coating process has been performed on triethanolamine-based electrolytes using a cooling bath. The nanostructure of obtained compound layers was examined with figure analysis of SEM nanographs. The effects of process variables (i.e., frequency, temperature of electrolytes, applied voltage, and treatment time) have been studied experimentally. Statistical methods were used to achieve the optimum size of nanocrystals. Finally, the contribution percentage of the effective factors of pulsed current was revealed, and confirmation showed the validity of obtained results. It has also been revealed that by changing the size of nanocrystalline carbonitrides, other properties of the coating will change significantly.     

A dynamic modeling to measure lean performance within lean attributes

In today’s competitive world lean manufacturing has become an important “role model” for two groups: academics and practitioners. Many organizations around the world have attempted to implement it but the lack of a clear understanding of the main attributes to leanness, lean performance and its measurement contribute to the failure of lean practices. It therefore seems necessary to provide a way to evaluate the impact of lean attributes using an approach to determine the criteria and key factors of leanness. Although there are numerous theoretical and practical studies that address lean tools and techniques, few studies focus systematically on measuring the influence of lean attributes on leanness. To fill the current gap, this paper presents an innovative approach to measure the value of the influence of lean attributes on manufacturing systems by using fuzzy membership functions. A lean attributes score is finally calculated to give managers and decision makers a real insight into the leanness level and to further improve it by acting appropriately in the manufacturing system. The model is dynamic, flexible, feasible, and easy to follow and implement. It enables a systematic measurement of the influence of lean attributes by producing a final integrated unit score.     

Adaptive yaw stability control by coordination of active steering and braking with an optimized lower-level controller

In this article, an integrated multiinput multioutput model reference adaptive control algorithm is presented based on active front steering and effective direct yaw moment distribution as an advanced driver assistance system. Vehicle parameter uncertainties in mass and tire-road friction coefficient are considered through adaptation laws at the upper level in the control structure. The efficient distribution of yaw moment on the rear wheels is performed via a constrained optimization at the lower control level. Control commands are executed by additive steering angle on front wheels and brake torque applied on one of the rear wheels. Simulation results for different lateral maneuvers are employed for the evaluation of the proposed adaptive control method. The performance of the integrated control algorithm to enhance vehicle handling and stability is shown on various road conditions.     

CoFe2O4@methyl cellulose core-shell nanostructure and their hybrids with functionalized graphene aerogel for high performance asymmetric supercapacitor

Recently, the use of asymmetric supercapacitors (ASC) has attracted much attention due to their optimum storage of energy and a high range of voltage. Here, we have indicated the design and fabrication of a unique ASC based on metal-spinel core-shell nanocomposite (CoFe₂O₄@MC) as a positive electrode and a p-phenylenediamine (PPDA)-graphene aerogel composite (AP) as a negative electrode in aqueous KOH electrolyte solution. The CoFe₂O₄@MC nanocomposite was prepared by the chemical deposition method. The AP was also effortlessly organized using the hydrothermal method. Considering the incorporation of methylcellulose carbohydrate polymer (MC) into the CoFe₂O₄ nanomaterial and consequently having a porous structure, a specific capacitance of 433.3 F g^?1 was obtained at the current density of 1 A g^?1 with the configuration of three electrodes. The CoFe₂O₄@MC//AP-ASC operates in the voltage range up to 2.3 V and provides a specific capacitance of 99 in 1 A g^?1. It presents an impressive energy density and power density of ~73 W h Kg^?1 and 1056 W kg^?1, respectively which prove its quality. The most important feature seems to be good cycling stability and capacity retention of 89% after 2000 cycles. These splendid outcomes show that CoFe₂O₄@MC nanocomposite possibly seems to be a satisfying choice for the next generation of devices with the capability of energy storage.     

TNF Is Partially Required for Cell-Death-Triggered Skin Inflammation upon Acute Loss of cFLIP

cFLIP is required for epidermal integrity and skin inflammation silencing via protection from TNF-induced keratinocyte apoptosis. Here, we generated and analyzed cFLIP epidermal KO mice with additional TNF deficiency. Intriguingly, the ablation of TNF rescued the pathological phenotype of epidermal cFLIP KO from characteristic weight loss and increased mortality. Moreover, the lack of TNF in these animals strongly reduced and delayed the epidermal hyperkeratosis and the increased apoptosis in keratinocytes. Our data demonstrate that TNF signaling in cFLIP-deficient keratinocytes is the critical factor for the regulation of skin inflammation via modulated cytokine and chemokine expression and, thus, the attraction of immune cells. Our data suggest that autocrine TNF loop activation upon cFLIP deletion is dispensable for T cells, but is critical for neutrophil attraction. Our findings provide evidence for a negative regulatory role of cFLIP for TNF-dependent apoptosis and partially for epidermal inflammation. However, alternative signaling pathways may contribute to the development of the dramatic skin disease upon cFLIP deletion. Our data warrant future studies of the regulatory mechanism controlling the development of skin disease upon cFLIP deficiency and the role of cFLIP/TNF in a number of inflammatory skin diseases, including toxic epidermal necrolysis (TEN).