LCZ696 Protects against Diabetic Cardiomyopathy-Induced Myocardial Inflammation,ER Stress,and Apoptosis through Inhibiting AGEs/NF-κB and PERK/CHOP Signaling Pathways

The present study is designed to determine the effect of LCZ696 on DCM in rats and investigate the underlying mechanism involved. Diabetes was induced by feeding rats with a high-fat diet for six weeks following a single injection of STZ (30 mg/kg). Diabetic rats were divided into three groups (n = 10). LCZ696 and valsartan treatment was started two weeks after diabetic induction and continued for eight weeks. At the end of the treatment, serum and cardiac tissues were analyzed by RT-PCR, Western blot, and ELISA kits. LCZ696 and valsartan ameliorated DCM progression by inhibiting AGEs formation at activity levels; pro-apoptotic markers (BAX/Bcl2 ratio and caspase-3) in mRNA and protein expressions, the NF-κB at mRNA; and protein levels associated with the restoration of elevated proinflammatory cytokines such as the TNF-α, IL-6, and IL-1β at the activity level. Furthermore, LCZ696 and valsartan contribute to restoring the induction of ER stress parameters (GRP78, PERK, eIF2a, ATF4, and CHOP) at mRNA and protein levels. LCZ696 and valsartan attenuated DCM by inhibiting the myocardial inflammation, ER stress, and apoptosis through AGEs/NF-κB and PERK/CHOP signaling cascades. Collectively, the present results reveal that LCZ696 had a more protective solid effect against DCM than valsartan.     

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

Moisture diffusion through (hexadecyltrimethylammonium bromide ‐ Indian bentonite)/(vinylester) nanocomposites in artificial seawater and demineralized water

This paper compares the moisture diffusion properties of organomodified (Indian Bentonite nanoclay)/vinylester containing different amounts of nanoclay on exposure to demineralized water and artificial seawater at room temperature. Moisture uptake behavior of (Indian Bentonite)/vinylester was investigated and compared with that of neat vinylester. Addition of 5 wt% nanoclay decreased the diffusivity and permeability of vinylester in artificial seawater medium, but these diffusion parameters increased in demineralized water medium. Degradation in glass transition temperature and microhardness of the nanocomposites were much greater in specimens aged in demineralized water than in those in artificial seawater medium. Moisture diffusion behavior of the specimens was analyzed by Fick's law and the Langmuir model. The aged specimens were chemically analyzed by using infrared spectroscopy after aging for 146 days. A significant amount of leached organic species was detected in the demineralized water–aged specimens but the same was absent in those aged in artificial seawater. J. VINYL ADDIT. TECHNOL., 22:441–451, 2016. © 2015 Society of Plastics Engineers     

X-ray investigation of sintered cadmium doped hydroxyapatites

Pure and cadmium (Cd) doped hydroxyapatites (HA, Ca₁₀(PO₄)₆(OH)₂) were synthesized by a precipitation method from aqueous solutions of Ca(NO₃)₂4·H₂O for the former and Cd(NO₃)₂4·H₂O for the latter, by using (NH₄)₂HPO₄ as the phosphate source, while pH was kept in the range of 11–12. The effect of incorporation of Cd²⁺ ions into the structure of HA was investigated after the air sintering at 1100 °C for 1 h. The results indicate that Cd²⁺ addition into HA yields nearly fully densified products with respect to pure stoichiometric HA. The XRD patterns showed that Cd doping increases the crystallinity of HA. The 2, 4.4, and 8.8 mol% Cd doped HAs had calcium oxide (CaO) impurity phase in their lattice. The CaO phase in the HA structure gradually disappeared with increasing Cd amount, and was replaced with cadmium oxide (CdO) in the CdHA doped with 11 mol% Cd. Cd²⁺ ion incorporation decreased the a- and c-axis lattice constants and unit cell volume of HA.     

Tuning fuzzy PD and PI controllers using reinforcement learning

In this paper, we propose a new auto-tuning fuzzy PD and PI controllers using reinforcement Q-learning (QL) algorithm for SISO (single-input single-output) and TITO (two-input two-output) systems. We first, investigate the design parameters and settings of a typical class of Fuzzy PD (FPD) and Fuzzy PI (FPI) controllers: zero-order Takagi–Sugeno controllers with equidistant triangular membership functions for inputs, equidistant singleton membership functions for output, Larsen’s implication method, and average sum defuzzification method. Secondly, the analytical structures of these typical fuzzy PD and PI controllers are compared to their classical counterpart PD and PI controllers. Finally, the effectiveness of the proposed method is proven through simulation examples.     

Electric load forecasting by using dynamic neural network

Electrical energy is fundamental for the wellbeing and for the economic development of any country. However, all countries must ensure access to essential resources and ensure the continuity of its supply. Due to the non-storable nature of electrical energy, the amount of consumed active power should always be equal the produced active power just to avoid power system frequency deviation problem. In order to keep the relationship production–consumption relation in compliance with different standards and to secure profitable operations of power system, electric load consumption must be predicted and controlled instantaneously. Several statistical and classical techniques are proposed in the literature but unfortunately all these methods are not accurate in a satisfactory manner. In this paper, a dynamic neural network is used for the prediction of daily power consumption. The suitability and the performance of the proposed approach is illustrated and verified with simulations on load data collected from French Transmission System Operator (RTE) website. The obtained results show that the accuracy and the efficiency are improved comparatively to conventional methods widely used in this field of research.     

Calibration of an Absolute Radiation Thermometer for Accurate Determination of Fixed-Point Temperatures

For accurate determinations of thermodynamic temperature, NPL has developed its absolute radiation thermometer (ART), which is calibrated traceably against a cryogenic radiometer. This article reviews some of the potential sources of systematic uncertainty present in the calibration and use of ART. In particular, this article is concerned with the evaluation of the size-of-source effect and the lens transmittance, as well as potential differences in the responsivity of a transfer trap detector when calibrated in terms of radiant power and used in irradiance mode.     

Antennas and Propagation for On-Body Communication Systems

On-body communication channels are of increasing interest for a number of applications, such as medical-sensor networks, emergency-service workers, and personal communications. This paper describes investigations into channel characterization and antenna performance at 2.45 GHz. It is shown that significant channel fading occurs during normal activity, due primarily to the dynamic nature of the human body, but also due to multipath around the body and from scattering by the environment. This fading can be mitigated by the use of antenna diversity, and gains of up to 10 dB are obtained. Separation of the antenna's performance from the channel characteristics is difficult, but results show that for many channels, an antenna polarized normal to the body's surface gives the best path gain. Simulation and modeling present many challenges, particularly in terms of the problem's scale, and the need for accurate modeling of the body and its movement.     

Influence of weathering on adhesion strength of chemically treated and coated Scotch pine

The objective of this study was to evaluate the effect of weathering on adhesion strength of Scotch pine (Pinus sylvestris L.) samples treated with three concentrations of Tanalith-E. Treated samples were also coated with polyurethane, synthetic and water based varnishes prior to 500 h accelerated weathering test. Adhesion strength between varnishing materials and substrate samples was determined employing pull-off type equipment. Based on the findings in this work adhesion strength values of samples decreased with increasing concentration of treatment chemical. The highest average strength value was found as 3.48 MPa for untreated control samples while 2.88 MPa was the lowest average value for the samples treated with Tanalith-E having 9% concentration and coated with water based varnish. Majority of the failures took place within the adhesion line between coating and the substrate with a very limited torn fibers. Results of statistical analysis revealed that samples coated with three different types of varnishes did not show any significant difference from each other at 95% confidence level. It was also found that chemical treatment of the samples adversely influenced their overall adhesion strength characteristics.