Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs

The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the “mutual prodrug” approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.     

Decentralized observers with consensus filters for distributed discrete-time linear systems

This paper presents a decentralized observer with a consensus filter for the state observation of discrete-time linear distributed systems. Each agent in the distributed system has an observer with a model of the plant that utilizes the set of locally available measurements, which may not make the full plant state detectable. This lack of detectability is overcome by utilizing a consensus filter that blends the state estimate of each agent with its neighbors’ estimates. It is proven that the state estimates of the proposed observer exponentially converge to the actual plant states under arbitrarily changing, but connected, communication and pseudo-connected sensing graph topologies. Except these connectivity properties, full knowledge of the sensing and communication graphs is not needed at the design time. As a byproduct, we obtained a result on the location of eigenvalues, i.e., the spectrum, of the Laplacian for a family of graphs with self-loops.     

Activities of MFI-Supported Rhenium Catalysts for the Aromatization of Methane: Effect of Cationic Form of the Inorganic Carrier

MFI type inorganic carrier was used in two different cationic forms, hydrogen and calcium respectively. MFI-supported molybdenum and rhenium catalysts were prepared. The activities of the catalysts were compared for the aromatization reaction of methane. Higher activity values were attained with the catalysts supported on HZSM-5. Aromatics were also observed with the catalysts supported on CaZSM-5, despite their deficiency in acid sites. Highly dispersed rhenium is expected to be formed with the use of the inorganic carrier in calcium form. On the other hand, lower reaction rates were observed with rhenium supported on CaZSM-5, in spite of the improved dispersion of the active rhenium species on this catalyst. This was interpreted in terms of the critical role of the acid sites in the conversion of methane to aromatics, compared to the improved dispersion of the active metal.     

Łukasiewicz logic and Riesz spaces

We initiate a deep study of Riesz MV-algebras which are MV-algebras endowed with a scalar multiplication with scalars from \([0,1]\) . Extending Mundici’s equivalence between MV-algebras and \(\ell \) -groups, we prove that Riesz MV-algebras are categorically equivalent to unit intervals in Riesz spaces with strong unit. Moreover, the subclass of norm-complete Riesz MV-algebras is equivalent to the class of commutative unital C \(^*\) -algebras. The propositional calculus \({\mathbb R}{\mathcal L}\) that has Riesz MV-algebras as models is a conservative extension of ?ukasiewicz \(\infty \) -valued propositional calculus and is complete with respect to evaluations in the standard model \([0,1]\) . We prove a normal form theorem for this logic, extending McNaughton theorem for ? ukasiewicz logic. We define the notions of quasi-linear combination and quasi-linear span for formulas in \({\mathbb R}{\mathcal L},\) and relate them with the analogue of de Finetti’s coherence criterion for \({\mathbb R}{\mathcal L}\) .     

A universal design resource for rich Internet applications based on design patterns

Rich Internet applications have removed most of the constraints of Web 1.0 while giving users more responsiveness and advanced browsing and interaction experiences. These new horizons, however, raise many challenges for people with disabilities or using limited hardware and software technologies, whose risk to be excluded from the benefits deriving from advanced web applications. To address this problem, WCAG 2.0 guidelines have been released as the newest World Wide Web Consortium recommendation for accessible web content, and WAI-ARIA is a candidate recommendation which provides reference specifications for accessible rich Internet applications. However, both specifications contain a huge amount of information that often discourages most web designers from dealing with accessibility issues. Moreover, guidelines are suitable and usually adopted to judge a design solution a posteriori, but they do not suggest how to face a design problem constructively. This paper proposes a design pattern language for accessibility. The language can be regarded as a universal design resource for helping web designers create accessible rich Internet applications compliant with the most recent standards. Knowledge representation through design patterns reflects the problem-solving approach usually followed by software and web designers, while pattern organization in a structured language aims to guide web designers throughout the design process. The language has been implemented as an accessible rich Internet application itself, thus allowing designers with disabilities to participate in web design. In order to evaluate the design pattern language, a three-step process was carried out including: (1) a heuristic analysis with a group of human–computer interaction experts, (2) a survey study with a group of web designers, and (3) a validation on the field with two designers who have been requested to apply the language in real design cases.     

Synthesis and properties of chitosan-modified poly(vinyl butyrate)

Modification of chitosan by grafting of vinyl butyrate was carried out in homogeneous phase using potassium persulfate as redox initator and 1.5% acetic acid as solvent. The percent grafting and grafting efficiency were analysed and the high grafting efficiency up to 94% was observed. The effects of reaction variables such as monomer concentration, initiator concentration, temperature and reaction time were investigated. It was observed that the solubility of chitosan was markedly reduced after grafting with vinyl butyrate. The grafted product is insoluble in common organic solvents as well in dilute organic and inorganic acids. Characterization of the graft copolymers were carried out by using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM) technics. Characteristic signal of carbonyl group was observed at 1,731 cm⁻¹ which belongs to the poly vinyl butyrate segments in the graft copolymer. The melting transition of the chitosan main chain in the copolymer shifted to 124°C from its original value 101°C. In addition to these, we have also studied topology of the graft copolymer and the SEM micrograph showed continuous homogenous matrix which means there is no phase separation.     

Aspects of nucleosomal positional flexibility and fluidity

Nucleosomes have been considered until recently to be stable and uniquely localized particles. We focus here on two properties of nucleosomes that are emerging as central attributes of their functions: mobility and multiplicity of localization. The biological relevance of these phenomena is based on the fact that chromatin functions depend on the relative stability of nucleosomes, on their covalent or conformational modifications, their dynamics, their localization, and the density of their distribution. In order to understand these complex behaviors both the structure of the nucleosome core particles and the informational rules governing their interaction with defined DNA sequences are here taken into consideration. The fact that nucleosomes solve the problem of how to locate a specific interaction site on a potentially infinite combination of sequences, with interactions recurring to a controlled level of informational ambiguity and stochasticity, is discussed. Nucleosomes have been shown to slide along DNA. This novel facet of their behavior and its implications in chromatin remodeling are reviewed.     

An investigation on wear behavior of UHMWPE/carbide composites at elevated temperatures

Ultra-high molecular weight polyethylene (UHMWPE) is extensively used in frictional applications due to its advanced wear resistance. This advanced polymer is reinforced with hard particulate fillers for further developments against wear conditions. Since elevated temperatures prevail in the service conditions, wear behavior of UHMWPE composites is an important issue for the engineering applications. In the present work, UHMWPE-based composites including silicon carbide (SiC) fillers were fabricated in a compression molding chamber. In the specimen preparation stage, molding pressure, filler amount, and filler particle size were varied to investigate the influence of these variables. Upon deciding the optimum parameters from the wear tests conducted at room temperature, the wear experiments were repeated for the optimum specimen at elevated temperatures, such as 40 and 60°C. According to the results, the wear behavior of the SiC/UHMWPE composites is heavily changed by the effect of elevated temperature. Adhesive effect is pronounced at elevated temperatures while the wear characteristics possess the abrasive effect in the sliding path. In addition, the composites exhibit an accelerated material loss as temperature increases during the frictional system.     

Improvements of the structural,thermal, and mechanical properties of structural adhesive with functionalized boron nitride nanoparticles

Investigations on the production and development of nanoparticle-reinforced polymer materials have been attracted attention by researchers. Various nanoparticles have been used to improve the mechanical, chemical, thermal, and physical properties of polymer matrix composites. Boron compounds come to the fore to improve the mechanical and thermal properties of polymers. In this study, mechanical, thermal, and structural properties of structural adhesive have been examined by adding nano hexagonal boron nitride (h-BN) to epoxy matrix at different percentages (0.5, 1, 2, 3, 4, and 5%). For this purpose, nano h-BN particles were functionalized with 3-aminopropyltriethoxysilane (APTES) to disperse the h-BN nanoparticles homogeneously in epoxy matrix and to form a strong bond at the matrix interface. Two-component structural epoxy adhesive was modified by using functionalized h-BN nanoparticles. The structural and thermal properties of the modified adhesives were investigated by scanning electron microscopy and energy dispersion X-ray spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis techniques. Tensile test and dynamic mechanical analysis were performed to determine the mechanical properties of the adhesives. When the results obtained from analysis were examined, it was seen that the nano h-BN particles functionalized with APTES were homogeneously dispersed in the epoxy matrix and formed a strong bond. In addition that, it was concluded from the experimental results that the thermal and mechanical properties of adhesives were improved by adding functionalized nano h-BN particles into epoxy at different ratios.     

Structural,thermal, and mechanical properties of silanized boron carbide doped epoxy nanocomposites

In the presented study, the structural, thermal, and mechanical properties of the nanocomposites were investigated by doping silanized hexagonal boron carbide (h-B₄C) nanoparticles in varying proportions (0.5%, 1%, 2%, 3%, 4%, and 5%) into the epoxy resin by weight. For this purpose, the surfaces of h-B₄C nanoparticles were silanized by using 3-(glycidyloxypropyl) trimethoxysilane (GPS) to improve adhesion between h-B₄C nanoparticles and epoxy matrix. Then, the silanized nanoparticles were added to the resin by ultrasonication and mechanical stirring techniques to produce nanocomposites. The bond structure differences of silanized B₄C nanoparticles (s-B₄C) and nanoparticle doped composites were investigated by using Fourier transform infrared spectroscopy. Scanning electron microscopy and energy dispersion X-ray spectroscopy (SEM-EDS) technique was used to examine the distribution of nanoparticles in the modified nanocomposites. Differential scanning calorimetry and thermogravimetric analysis techniques were used to determine the thermal properties of the neat and s-B₄C doped nanocomposites. The tensile test and dynamic mechanical analysis were performed to determine the mechanical properties. When the experimental results were examined, changes in the bonding structure of the s-B₄C nanoparticles doped nanocomposites and significant improvements in the mechanical and thermal properties were observed. The optimum doping ratio was determined as 2% by weight. At this doping ratio, the T_g, tensile strength and storage modulus increased approximately 18%, 35%, and 44% compared to the neat composite, respectively.