Tailoring the Release Rates of Fluconazole Using Solid Dispersions in Polymer Blends

Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.     

Synthesis of aluminium nanoparticles by arc plasma spray under atmospheric pressure

The present study addresses the feasibility to synthesize aluminium nanoparticles (NPs) from micron-sized aluminium powder with the use of a customized atmospheric plasma spraying (APS) technique. Using APS, nanoparticle synthesis can be achieved via rapid melting and vaporization of the initial micrometric particles and their subsequent re-nucleation. A custom mantle system was designed and developed with the aid of relevant simplified CFD simulations. The mantle provided the necessary inert environment (argon), at ambient pressure, in order to avoid any oxidation of the metal during plasma spraying while promoted rapid quenching of the gasified metal. The particles formed were collected with the aid of a quartz filter downstream of the plasma flame and the production rate achieved was 2 g min^?1. Ex situ post-characterization of the particles via X-ray diffraction, specific surface area measurement (BET), transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and thermogravimetric analysis (TGA) under air revealed that the powders obtained primarily comprised of monocrystalline metallic aluminium nanoparticles of almost spherical shape. The NPs possessed a 2–5 nm oxide coating layer. By regulating the conditions inside the mantle, a variety of different size distributions were obtained.     

Elliott Wave Theory and neuro-fuzzy systems,in stock market prediction: The WASP system

This paper presents the WASP (Wave Analysis Stock Prediction) system, a system based on the neuro-fuzzy architecture, which utilizes aspects from the Elliott Wave Theory, presented by Ralph Nelson Elliott. This theory has been found to be extremely useful and accurate, particularly in problems of forecasting. A neuro-fuzzy logic technique has been used to forecast the trend of the stock prices and the results derived are very encouraging.     

Security model for emergency real-time communications in autonomous networks

Towards the proliferation of architectures, tools and applications that have the potential to be used during an emergency rescue mission, we present a framework for emergency real-time communication using autonomous networks, called emergency Mobile Ad-hoc Networks (eMANETs). By eMANETs we refer to networks that are deployed in emergency cases where default telecommunications infrastructure has failed. Our goal is to design a security framework that will secure real-time communications during emergency rescue scenarios. The proposed framework consists of a secure routing protocol, intrusion detection provision and security extension for real-time communications using peer-to-peer overlays. We envisage that the results of this work will aid and serve the needs of any society against any event that threatens serious damage to human welfare or to the environment.     

Forecasting Development of Mine Pit Lake Water Surface Levels Based on Time Series Analysis and Neural Networks

Sustainable mine closure is one of the main priorities of the mining industry. This aim of this research was to predict the spatiotemporal development of water levels in a mined-out pit by generating forecasts of the dependent variables (rainfall and temperature) via linear (autoregressive integrated moving average) and non-linear (artificial neural network) models. We investigated natural water level development in one mined-out pit of the closed lignite mines in Amynteon, north Greece, with no artificial recharge. The forecasted rate of water level increase was estimated to be ≈ 10 m per year in the ‘early’ stage of pit lake spatiotemporal evolution (first 10 years), and 0.1 m per year in the ‘last’ stage of potential lake development (after year 2060). Also, the optimum lake surface (i.e. the level where no significant increase in water level rate appears) was estimated at?+?520 m, which was predicted to occur in ≈ 40 years. The proposed methodology was validated via water level measurements performed during the first year of lake development, where field measurements of water elevations closely followed predictions. Forecasting pit lake water levels is essential for strategic planning, examining pit lake repurposing options, and informing decisions about post-mining futures and economic transitions.

     

The Discovery of a Highly Selective 5,6,7,8‐Tetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson’s Disease Model

Sirtuins, NAD⁺‐dependent histone deacetylases (HDACs), have recently emerged as potential therapeutic targets for the treatment of a variety of diseases. The discovery of potent and isoform‐selective inhibitors of this enzyme family should provide chemical tools to help determine the roles of these targets and validate their therapeutic value. Herein, we report the discovery of a novel class of highly selective SIRT2 inhibitors, identified by pharmacophore screening. We report the identification and validation of 3‐((2‐methoxynaphthalen‐1‐yl)methyl)‐7‐((pyridin‐3‐ylmethyl)amino)‐5,6,7,8‐tetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one (ICL‐SIRT078), a substrate‐competitive SIRT2 inhibitor with a K_i value of 0.62±0.15 μM and more than 50‐fold selectivity against SIRT1, 3 and 5. Treatment of MCF‐7 breast cancer cells with ICL‐SIRT078 results in hyperacetylation of α‐tubulin, an established SIRT2 biomarker, at doses comparable with the biochemical IC₅₀ data, while suppressing MCF‐7 proliferation at higher concentrations. In concordance with the recent reports that suggest SIRT2 inhibition is a potential strategy for the treatment of Parkinson’s disease, we find that compound ICL‐SIRT078 has a significant neuroprotective effect in a lactacystin‐induced model of Parkinsonian neuronal cell death in the N27 cell line. These results encourage further investigation into the effects of ICL‐SIRT078, or an optimised derivative thereof, as a candidate neuroprotective agent in in vivo models of Parkinson’s disease.     

Using adaptive neuro-fuzzy inference systems for the detection of centroblasts in microscopic images of follicular lymphoma

In this paper, a complete methodology for automatic detection of centroblasts (CBs) in microscopic images acquired from tissue biopsies of follicular lymphoma is presented. In the proposed method, tissue sections are sliced at a low thickness level, around 1–1.5 \(\upmu \)m, which provides a more detailed depiction of the nuclei and other textural information. Initially, images are segmented into their basic cytological components, i.e., blood cells, nuclei and extra-cellular material, and then a novel touching-cell splitting algorithm is applied using a Gaussian mixture model and expectation–maximization algorithm. Additionally, a morphological and textural analysis of CBs is applied in order to extract various features related to their nuclei, nucleoli and cytoplasm. In the final step, a novel classification scheme is proposed based on adaptive neuro-fuzzy inference systems to classify the candidate cells. The methodology yielded promising results with an average detection rate of 90.35 %.     

Genetics of Food Preferences: A First View from Silk Road Populations

Abstract: Food preferences are the main factor driving food intake and choice. There are good reasons to suspect some genetic influence on food acceptance, not least because genetic factors are implicated in a number of factors that are likely to be related to food choice. In addition, some food dislikes show themselves early in life, before there is any evidence for aversive experiences. Although taste has been widely studied in regards of pure tastes such as bitter or sweet perception, the relationship between taste‐related genes and food preferences has seldom been explored. In this work we investigated relationship of 37 taste‐related genes with food preferences. The study was carried out during a scientific expedition through Caucasus and Central Asia (Silk Road) analyzing more than 400 samples from 5 different countries. A food preference questionnaire was administered to each participant and a DNA sample was obtained. Other information, such as age, sex, life style and anthropometrical measures, were also collected. We found significant associations with variants of: (1) TAS1R2 [Correction added after initial online publication on 27 Aug 2012. TAS1R3 was changed to TAS1R2.] gene and liking of Vodka (P= 1.6 × 10^?3), white wine (P= 4.0 × 10^?4) and lamb meat (P= 1.6 × 10^?3); (2) PCLB2 gene and preference for Hot Tea (P= 8.0 × 10^?4); (3) TPRV1 gene and beet liking (P= 3.8 × 10^?5); and (4) ITPR3 gene and liking of both lamb meat (5.8 × 10^?4) and sheep cheese (8.9×10^?4). These findings give a new insight on a better understanding, of genetic factors influencing food preferences which is critical to the development of effective dietary interventions, especially for people that may be genetically not predisposed for liking specific nutrients.     

Cutting with coated tools: Coating technologies,characterization methods and performance optimization

Coated tools constitute the majority of the tools applied in material removal processes, rendering the employment of uncoated ones as an exception. A broad growing market of coated cutting tools has been developed. Moreover, numerous material- and manufacturing-engineers have joint their expertise, aiming at developing coatings meeting the needs for processing the most difficult-to-cut materials at the most extreme cutting conditions. The emerging of new workpiece, tool and film materials, the evolution of sophisticated coatings’ characterization methods and the continuous need for higher productivity rates, maintain vivid the industrial and scientific interest for further advancing this field.     

Development and characterization of oligonucleotide-tagged dye-encapsulating EPC/DPPG liposomes

Liposomes applications in health care include meanly their ability to carry drugs and genes inside the human body for therapeutic purposes. Nevertheless their applicability can extend far beyond and could be used as analytical tools in order to perform rapid, low-cost, sensitive and specific analyses. Their physical characteristics, such as large internal volume and extended surface area, render them ideal for these applications and specifically for improving the specificity and sensitivity of the analytical assay. The purpose of this study was to develop a simple, stable and low-cost oligonucleotide-tagged liposomal formulation consisting of EggPC and DPPG with a simple to synthesize thiol-reactive conjugate (Mal-SA) incorporated into the lipid bilayer of liposomes. The prepared liposomes, having also the water soluble dye Sulforhodamine B encapsulated in their inner cavity, were characterized in terms of their physicochemical (size, size distribution, zeta-potential, lipid content) and mechanical (morphology, rigidity) properties. The results showed that the final liposomal formulation could be used in the future as analytical tool for detecting pathogen strains of microorganism in biological milieu.