Bayesian Copulae Distributions, with Application to Operational Risk Management

The aim of this paper is to introduce a new methodology for operational risk management, based on Bayesian copulae. One of the main problems related to operational risk management is understanding the complex dependence structure of the associated variables. In order to model this structure in a flexible way, we construct a method based on copulae. This allows us to split the joint multivariate probability distribution of a random vector of losses into individual components characterized by univariate marginals. Thus, copula functions embody all the information about the correlation between variables and provide a useful technique for modelling the dependency of a high number of marginals. Another important problem in operational risk modelling is the lack of loss data. This suggests the use of Bayesian models, computed via simulation methods and, in particular, Markov chain Monte Carlo. We propose a new methodology for modelling operational risk and for estimating the required capital. This methodology combines the use of copulae and Bayesian models.      

Apoptosis induction and mitochondria alteration in human HeLa tumour cells by photoproducts of Rose Bengal acetate

The aim of this work was to investigate the apoptosis induction and mitochondria alteration after photodamage exerted by incubation of HeLa cells with Rose Bengal acetate-derivative (RBAc) followed by irradiation for a total dose of 1.6 J/cm2. This treatment was previously demonstrated to reduce cell viability under mild treatment conditions, suggesting the restoration of the photoactive molecule in particularly sensitive cell sites. Indeed, Rose Bengal (RB) is a very efficient photosensitizer, whose photophysical properties are inactivated by addition of the quencher group acetate. The RBAc behaves as a fluorogenic substrate by entering easily the cells where the original, photoactive molecule is restored by specific esterases. Different intracellular sites of photodamage of RB are present. In particular, fluorescence imaging of Rodamine 123 and JC-1 labelled cells showed altered morphology and loss of potential membrane of mitochondria. MTT and NR assays gave indications of alteration of mitochondrial and lysosomal enzyme activities. These damaged sites were likely responsible for triggering apoptosis. Significant amount of apoptotic cell death (about 40%) was induced after light irradiation followed RBAc incubation as revealed by morphological (modification of cell shape and blebs formation), cytochemical (FITC-Annexin-V positive cells) and nuclear fragmentation assays.     

Montmorillonite as an adsorbent for extraction and concentration of atrazine, propazine, deethylatrazine, deisopropylatrazine and hydroxyatrazine

Adsorption properties of the clay mineral montmorillonite in the potassium homoionic form (KMT) was investigated to achieve the extraction and concentration of the herbicides atrazine (AT) and propazine (PROP), as well as the main degradation products of atrazine, namely deethylatrazine (DEA), deisopropylatrazine (DIA) and hydroxyatrazine (ATOH). A batch approach was proposed, with recovery percentages for AT, PROP and DIA higher than 90% at concentrations of 0.50 and 2.50 μg L⁻¹. For DEA and ATOH, however, low recoveries were obtained. For DEA, this fact can be explained by its low K_d with KMT, contrary to ATOH, which interacts strongly with the mineral surface, hindering the complete desorption and hence, generating low recovery percentages. The influence of pH, ionic strength and humic acid was studied, and a comparison with the C₁₈ phase as SPE cartridges was carried out. Montmorillonite showed a similar performance to commercial cartridge for concentrations of AT, DEA and PROP, but better recoveries for DIA was obtained using the clay mineral. For ATOH the recovery was also higher on the clay mineral, although for this compound the most suitable SPE cartridge is constituted by cation exchange resin. After the concentration and elution steps, the 0.50 and 2.50 μg L⁻¹ gave chromatographic peak areas that could be easily quantified with an analytical curve obtained in the concentration range between 7.5 and 100 μg L⁻¹. The obtained concentration factors are suitable to allow the application of the method to the monitoring of triazine residues in drinking water.     

A liquid chromatography‐atmospheric pressure photoionization tandem mass spectrometric (LC‐APPI‐MS/MS) method for the determination of triterpenoids in medicinal plant extracts

An analytical method using liquid chromatography‐atmospheric pressure photoionization tandem mass spectrometry with toluene as a dopant was developed for the determination of triterpenes in medicinal plant extracts. The 12 compounds determined have been shown to exhibit biological activity, such as gastroprotective, hepatoprotective, anti‐inflammatory, antiviral and anti‐tumor effects. The parameters of the atmospheric pressure photoionization interface were optimized to obtain the highest possible sensitivity for all of the compounds. The limits of detection and quantification ranged from 0.4 to 157.9 µg l^?1 and 1.3 to 526.4 µg l^?1, respectively. The method was validated and applied to extracts of five medicinal plants species (Mansoa alliacea (Lam.) A.H.Gentry, Bauhinia variegata var variegata, Bauhinia variegata var alboflava, Cecropia obtuse Trécul and Cecropia palmate Willd) from the Amazonian region. The concentrations of the six triterpenes quantified in the samples ranged from 0.424 mg kg^?1 for ursolic acid to 371.96 mg kg^?1 for β‐amyrin, which were quantified by using the standard addition method (n = 3). Copyright © 2016 John Wiley & Sons, Ltd.     

Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6‐Selective Integrin Ligands

The αvβ6 integrin binds the RGD‐containing peptide of the foot and mouth disease virus with high selectivity. In this study, the long binding helix of this ligand was downsized to an enzymatically stable cyclic peptide endowed with sub‐nanomolar binding affinity toward the αvβ6 receptor and remarkable selectivity against other integrins. Computational studies were performed to disclose the molecular bases underlying the high binding affinity and receptor subtype selectivity of this peptide. Finally, the utility of the ligand for use in biomedical studies was also demonstrated here.     

Laboratory tests addressed to realize customized restoration procedures of underwater archaeological ceramic finds

The present contribution is part of a biennial research project funded by the Italian Ministry of Education, Universities and Research (MIUR). This study, currently in progress, deals with innovative experimental approaches applied to the chemical, mineralogical and physical transformations occurring during the prolonged permanence of archaeological ceramic finds in seawater environments as well as to restoration and conservation issues of the same underwater artifacts. The experimental approach used in this research consisted in the manufacture of ceramic test-pieces (briquettes) and their successive placing in underwater environment. This work aims at assessing how textural and compositional parameters along with firing temperatures of a ceramic paste could affect total porosity, pore size distribution and kinetics of capillary water absorption. A further purpose is concerned with the study of the potential modification of porosity and pore size distribution in the same ceramic bodies after immersion in seawater (3 and 6 months). The study was carried out using a multi-technique approach including investigations through polarized light microscopy (PLM), capillary water absorption test, mercury intrusion porosimetry (MIP) analyses and theoretical calculation of salt crystallization pressures. The obtained results show a different behavior of the six experimental pastes as a function of their compositional and textural features as well as pore size distribution and firing temperatures. These parameters, in various extents, have been found significantly influencing the kinetics of water absorption and the susceptibility of ceramic artifacts to salt crystallization processes, with important implications on conservation procedures needed before the musealization.     

Isolation and structure elucidation of ovatoxin-a, the major toxin produced by Ostreopsis ovata

Since 2005, the benthic dinoflagellate Ostreopsis cf. ovata has bloomed across the Mediterranean basin, provoking serious toxic outbreaks. LC/MS studies have identified a number of palytoxin-like compounds, termed ovatoxins, along with trace amounts of putative palytoxin as the causative agents of the O. cf. ovata -related human sufferings. So far, any risk assessment for ovatoxins as well as establishment of their allowance levels in seafood has been prevented by the lack of pure toxins. The present paper reports on the isolation, NMR-based structural determination, and preliminary mouse lethality evaluation of ovatoxin-a, the major toxic compound contained in O. cf. ovata extracts. Availability of pure ovatoxin-a will open the double prospect of fully evaluating its toxicity and preparing reference standards to be employed in LC/MS quantitative analyses. Elucidation of ovatoxin-a's complex structure will ultimately herald the understanding of the molecular bases of ovatoxins bioactivity.     

Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis

Background  

Multiple sclerosis (MS) varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression. Attention was focused on markers of myelination (MBP and PDGFαR) and neuronal distress and/or damage (GABA synthesis enzymes, GAD65 and GAD67, NGF, BDNF and related receptors), in two CNS areas, i.e. spinal cord and cerebellum, which are respectively severely and mildly affected by inflammation and demyelination. Tissues were sampled during acute, relapse/remission and chronic phases and results were analysed by two-way ANOVA.     

New indole alkaloid from Peschiera affinis (Apocynaceae)

A new indole alkaloid of the pyridocarbazole type, named 6N-hydroxy-olivacine, and two known compounds, 2N-oxide-olivacine and olivacine, were isolated from roots of Peschiera affinis. The structures of the compounds were determined by spectroscopic {IR and extensive NMR (COSY, HMQC, HMBCand NOESY)} and EIMS analysis.     

Comparative computational studies of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives as potential antinociceptive agents

In this study, the antinociceptive properties of 3,4-dihydro-2,6-diaryl-4-oxo-pyrimidine-5-carbonitrile derivatives 5a-i at doses of 25 and 50 mg/kg were evaluated in mice, using the abdominal constriction test. Molecular modeling studies were also performed using density functional theory calculations. These data provided information about the electrostatic and ionization potentials and were used to compare the antinociceptive activity of the title compounds. The most active compounds were 3,4-dihydro-2-(4-chlorophenyl)-6-(4-methoxyphenyl)-4-oxo-pyrimidine-5-carbonitrile (5b) and 3,4-dihydro-2,6-diphenyl-4-oxo-pyrimidine-5-carbonitrile (5i), which inhibited the number of abdominal constrictions, at 50 mg/kg dose, in 88.6% and 88% of the sample, respectively. A preliminary SAR study demonstrated that halogen replacement in the phenyl rings of the compounds under study reduces the antinociceptive activity. DFT calculations showed that there is a high correlation between the ionization potentials and the analgesic properties of the compounds. It was found that compounds with a positive ionization potential (compounds 5b and 5i) were found to be the best analgesic drugs in this series.