From efficiency to optimality in proportional reinsurance under group correlation

Based on our recent discovery of closed form formulae of efficient Mean Variance retentions in variable quota-share proportional reinsurance under group correlation, we analyzed the influence of different combination of correlation and safety loading levels on the efficient frontier, both in a single period stylized problem and in a multiperiod one.

On the solubility of three disperse anthraquinone dyes in supercritical carbon dioxide: new experimental data and correlation

Solubility measurements of quinizarin. (1,4-dihydroxyanthraquinone), disperse red 9 (1-(methylamino) anthraquinone), and disperse blue 14 (1,4-bis(methylamino)anthraquinone) in supercritical carbon dioxide (SC CO2) were carried out in a flow type apparatus, at a temperature range from (333.2 to 393.2) K and at pressures from (12.0 to 40.0) MPa. Mole fraction solubility of the three dyes decreases in the order quinizarin (2.9 x 10(-6) to 2.9.10(-4)), red 9 (1.4 x 10(-6) to 3.2 x 10(-4)), and blue 14 (7.8 x 10(-8) to 2.2 x 10(-5)). Four semiempirical density based models were used to correlatethe solubility of the dyes in the SC CO2. From the correlation results, the total heat of reaction, heat of vaporization plus the heat of solvation of the solute, were calculated and compared with the results presented in the literature. The solubilities of the three dyes were correlated also applying the Soave-Redlich-Kwong cubic equation of state (SRK CEoS) with classical mixing rules, and the physical properties required for the modeling were estimated and reported.

In vivo and in vitro effects of RAD001 on bladder cancer

Objective: To evaluate the influence of Everolimus (RAD001) on chemically induced urothelial lesions in mice and its influence on in vitro human bladder cancer cell lines. Methods: ICR male mice were given N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for a period of 12 weeks. Subsequently, RAD001 was administered via oral gavage, for 6 weeks. At the end of the experiment, all the animals were sacrificed and tumor development was determined by means of histopathologic evaluation; mammalian target of rapamycin (mTOR) expressivity was evaluated by immunohistochemistry. Three human bladder cancer cell lines (T24, HT1376, and 5637) were treated using a range of RAD001 concentrations. MTT assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to assess cell proliferation, apoptosis index, and cell cycle analysis, respectively. Immunoblotting analysis of 3 cell line extracts using mTOR and Akt antibodies was performed in order to study the expression of Akt and mTOR proteins and their phosphorylated forms. Results: The incidence of urothelial lesions in animals treated with RAD001 was similar to those animals not treated. RAD001 did not block T24 and HT1376 cell proliferation or induce apoptosis. A reduction in cell proliferation rate and therefore G0/G1 phase arrest, as well as a statistically significant induction of apoptosis (P 0.001), was only observed in the 5637 cell line. Conclusion: RAD001 seems not to have a significant effect on chemically induced murine bladder tumors. The effect of RAD001 on tumor proliferation and apoptosis was achieved only in superficial derived bladder cancer cell line, no effect was observed in invasive cell lines.

Experimental Measurements and Correlation of the Solubility of Three Primary Amides in Supercritical CO2: Acetanilide, Propanamide, and Butanamide

Solubilities of three primary amides, namely, acetanilide, propanamide, and butanamide, in supercritical carbon dioxide were measured at T = (308.2, 313.2, and 323.2) K over the pressure range (9.0 to 40.0) MPa by a flow type apparatus. The solubility behavior of the three solids shows an analogous trend with a crossover region of the respective isotherms between (12 to 14) MPa. The solubility of each amide, at the same temperature and pressure, decreases from propanamide to acetanilide. Pure compound properties required for the modeling were estimated, and the solubilities of the amides were correlated by using the Soave-Redlich-Kwong cubic equation of state with an absolute average relative deviation (AARD) from (1.3 to 6.1) %.

Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(eta(6)-cymene)(bha)Cl] complexes

The ruthenium(II)-cymene complexes [Ru(eta(6)-cymene)(bha)Cl] with substituted halogenobenzohydroxamato (bha) ligands (substituents = 4-F, 4-Cl, 4-Br, 2,4-F-2, 3,4-F-2, 2,5-F-2, 2,6-F-2) have been synthesized and characterized by elemental analysis, IR, H-1 NMR, C-13 NMR, cyclic voltammetry and controlled-potential electrolysis, and density functional theory (DFT) studies. The compositions of their frontier molecular orbitals (MOs) were established by DFT calculations, and the oxidation and reduction potentials are shown to follow the orders of the estimated vertical ionization potential and electron affinity, respectively. The electrochemical E-L Lever parameter is estimated for the first time for the various bha ligands, which can thus be ordered according to their electron-donor character. All complexes exhibit very strong protein tyrosine kinase (PTK) inhibitory activity, even much higher than that of genistein, the clinically used PTK inhibitory drug. The complex containing the 2,4-difluorobenzohydroxamato ligand is the most active one, and the dependences of the PTK activity of the complexes and of their redox potentials on the ring substituents are discussed. (C) 2012 Elsevier B.V. All rights reserved.

Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production

Background - According to the Report on Carcinogens, formaldehyde ranks 25th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Presently, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans (Group 1), based on sufficient evidence in humans and in experimental animals. Manyfold in vitro studies clearly indicated that formaldehyde can induce genotoxic effects in proliferating cultured mammalian cells. Furthermore, some in vivo studies have found changes in epithelial cells and in peripheral blood lymphocytes related to formaldehyde exposure. Methods - A study was carried out in Portugal, using 80 workers occupationally exposed to formaldehyde vapours: 30 workers from formaldehyde and formaldehyde-based resins production factory and 50 from 10 pathology and anatomy laboratories. A control group of 85 non-exposed subjects was considered. Exposure assessment was performed by applying simultaneously two techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection equipment with simultaneously video recording. Evaluation of genotoxic effects was performed by application of micronucleus test in exfoliated epithelial cells from buccal mucosa and peripheral blood lymphocytes. Results - Time-weighted average concentrations not exceeded the reference value (0.75 ppm) in the two occupational settings studied. Ceiling concentrations, on the other hand, were higher than reference value (0.3 ppm) in both. The frequency of micronucleus in peripheral blood lymphocytes and in epithelial cells was significantly higher in both exposed groups than in the control group (p < 0.001). Moreover, the frequency of micronucleus in peripheral blood lymphocytes was significantly higher in the laboratories group than in the factory workers (p < 0.05). A moderate positive correlation was found between duration of occupational exposure to formaldehyde (years of exposure) and micronucleus frequency in peripheral blood lymphocytes (r = 0.401; p < 0.001) and in epithelial cells (r = 0.209; p < 0.01). Conclusions - The population studied is exposed to high peak concentrations of formaldehyde with a long-term exposure. These two aspects, cumulatively, can be the cause of the observed genotoxic endpoint effects. The association of these cytogenetic effects with formaldehyde exposure gives important information to risk assessment process and may also be used to assess health risks for exposed workers.

Synthesis and characterization of rabies virus glycoprotein-tagged amphiphilic cyclodextrins for siRNA delivery in human glioblastoma cells: in vitro analysis

In man brain cancer is an aggressive, malignant form of tumour, it is highly infiltrative in nature, is associated with cellular heterogeneity and affects cerebral hemispheres of the brain. Current drug therapies are inadequate and an unmet clinical need exists to develop new improved therapeutics. The ability to silence genes associated with disease progression by using short interfering RNA (siRNA) presents the potential to develop safe and effective therapies. In this work, in order to protect the siRNA from degradation, promote cell specific uptake and enhance gene silencing efficiency, a PEGylated cyclodextrin (CD)-based nanoparticle, tagged with a CNS-targeting peptide derived from the rabies virus glycoprotein (RVG) was formulated and characterized. The modified cyclodextrin derivatives were synthesized and co-formulated to form nanoparticles containing siRNA which were analysed for size, surface charge, stability, cellular uptake and gene-knockdown in brain cancer cells. The results identified an optimised co-formulation prototype at a molar ratio of 1:1.5:0.5 (cationic cyclodextrin:PEGylated cyclodextrin:RVG-tagged PEGylated cyclodextrin) with a size of 281±39.72nm, a surface charge of 26.73±3mV, with efficient cellular uptake and a 27% gene-knockdown ability. This CD-based formulation represents a potential nanocomplex for systemic delivery of siRNA targeting brain cancer.

In vitro assessment of three dimensional dense chitosan-based structures to be as bioabsorbable implants

Chitosan biocompatibility and biodegradability properties make this biopolymer promising for the development of advanced internal fixation devices for orthopedic applications. This work presents a detailed study on the production and characterization of three dimensional (3D) dense, non-porous, chitosan-based structures, with the ability to be processed in different shapes, and also with high strength and stiffness. Such features are crucial for the application of such 3D structures as bioabsorbable implantable devices. The influence of chitosan's molecular weight and the addition of one plasticizer (glycerol) on 3D dense chitosan-based products' biomechanical properties were explored. Several specimens were produced and in vitro studies were performed in order to assess the cytotoxicity of these specimens and their physical behavior throughout the enzymatic degradation experiments. The results point out that glycerol does not impact on cytotoxicity and has a high impact in improving mechanical properties, both elasticity and compressive strength. In addition, human mesenchymal stem/stromal cells (MSC) were used as an ex-vivo model to study cell adhesion and proliferation on these structures, showing promising results with fold increase values in total cell number similar to the ones obtained in standard cell culture flasks. (C) 2014 Elsevier Ltd. All rights reserved.

Color and Luminescence stability of selected dental materials in vitro

To study luminescence, reflectance, and color stability of dental composites and ceramics. Materials and Methods: IPS e.max, IPS Classic, Gradia, and Sinfony materials were tested, both unpolished (as-cast) and polished specimens. Coffee, tea, red wine, and distilled water (control) were used as staining drinks. Disk-shaped specimens were soaked in the staining drinks for up to 5 days. Color was measured by a colorimeter. Fluorescence was recorded using a spectrofluorometer, in the front-face geometry. Time-resolved fluorescence spectra were recorded using a laser nanosecond spectrofluorometer. Results: The exposure of the examined dental materials to staining drinks caused changes in color of the composites and ceramics, with the polished specimens exhibiting significantly lower color changes as compared to unpolished specimens. Composites exhibited lower color stability as compared to ceramic materials. Water also caused perceptible color changes in most materials. The materials tested demonstrated significantly different initial luminescence intensities. Upon exposure to staining drinks, luminescence became weaker by up to 40%, dependent on the drink and the material. Time-resolved luminescence spectra exhibited some red shift of the emission band at longer times, with the lifetimes in the range of tens of nanoseconds. Conclusions: Unpolished specimens with a more developed surface have lower color stability. Specimens stored in water develop some changes in their visual appearance. The presently proposed methods are effective in evaluating the luminescence of dental materials. Luminescence needs to be tested in addition to color, as the two characteristics are uncorrelated. It is important to further improve the color and luminescence stability of dental materials.

"In-vitro" corrosion behaviour of the magnesium alloy with Al and Zn (AZ31) protected with a biodegradable polycaprolactone coating loaded with hydroxyapatite and cephalexin

Mg alloys are very susceptible to corrosion in physiological media. This behaviour limits its widespread use in biomedical applications as bioresorbable implants, but it can be controlled by applying protective coatings. On one hand, coatings must delay and control the degradation process of the bare alloy and, on the other hand, they must be functional and biocompatible. In this study a biocompatible polycaprolactone (PCL) coating was functionalised with nano hydroxyapatite (HA) particles for enhanced biocompatibility and with an antibiotic, cephalexin, for anti-bacterial purposes and applied on the AZ31 alloy. The chemical composition and the surface morphology of the coated samples, before and after the corrosion tests, were studied by scanning electron microscopy (SEM) coupled with energy dispersive x-ray analysis (EDX) and Raman. The results showed that the presence of additives induced the formation of agglomerates and defects in the coating that resulted in the formation of pores during immersion in Hanks' solution. The corrosion resistance of the coated samples was studied in Hank's solution by electrochemical impedance spectroscopy (EIS). The results evidenced that all the coatings can provide corrosion protection of the bare alloy. However, in the presence of the additives, corrosion protection decreased. The wetting behaviour of the coating was evaluated by the static contact angle method and it was found that the presence of both hydroxyapatite and cephalexin increased the hydrophilic behaviour of the surface. The results showed that it is possible to tailor a composite coating that can store an antibiotic and nano hydroxyapatite particles, while allowing to control the in-vitro corrosion degradation of the bioresorbable Mg alloy AZ31. (C) 2015 Elsevier Ltd. All rights reserved.

Solubilities of C‑Tetraalkylcalix[4]resorcinarenes in SCCO2: experimental measurements, characterization, and correlation

The solubilities of two C-tetraalkylcalix[4]resorcinarenes, namely C-tetramethylcalix[4]resorcinarene and C-tetrapentylcalix[4]resorcinarene, in supercritical carbon dioxide (SCCO2) were measured in a flow-type apparatus at a temperature range from (313.2 to 333.2) K and at pressures from (12.0 to 35.0) MPa. The C-tetraalkylcalix[4]resorcinarenes were synthesized applying our optimized procedure and fully characterized by means of gel permeation chromatography, infrared and nuclear magnetic resonance spectroscopy. The solubilities of the C-tetraalkylcalix[4]resorcinarenes in SCCO2 were determined by analysis of the extracts obtained by HPLC with ultraviolet (UV) detection methodology adapted by our team. Four semiempirical density-based models, and the SoaveRedlichKwong cubic equation of state (SRK CEoS) with classical mixing rules, were applied to correlate the solubility of the calix[4]resorcinarenes in the SC CO2. The physical properties required for the modeling were estimated and reported.