A 3D QSAR approach to the search for geometrical similarity in a series of nonpeptide angiotensin II receptor antagonists

Summary A 3D QSAR methodology based on the combined use of conformational analysis and chemometrics was applied to perform a comparative analysis of the 3D conformational features of 13 nonpeptide angiotensin II receptor antagonists showing different levels of binding affinity. Conformational analysis by using a molecular mechanics MM2 method was carried out for each of these structures to obtain conformational minima. These minima were described by ten interatomic distances which define the relative spatial disposition of five significant atoms belonging to relevant functional groups present in all the 13 molecules. The structure-activity relationship between the interatomic distances and the biological activity was then assessed by using chemometric methods (cluster analysis, principal component analysis, classification methods). With our indirect approach based on the search for geometrical similarity it was possible, even though structural information on the receptor active site was lacking, to identify the 3D geometrical requirements for the binding affinity of nonpeptide angiotensin II receptor inhibitors.     

Increased viability of odontoblast-like cells subjected to low-level laser irradiation

Studies have shown that the increase of cell metabolism depends on the low level laser therapy (LLLT) parameters used to irradiate the cells. However, the optimal laser dose to up-regulate pulp cell activity remains unknown. Consequently, the aim of this study was to evaluate the metabolic response of odontoblast-like cells (MDPC-23) exposed to different LLLT doses. Cells at 20000 cells/cm² were seeded in 24-well plates using plain culture medium (DMEM) and were incubated in a humidified incubator with 5% CO₂ at 37°C. After 24 h, the culture medium was replaced by fresh DMEM supplemented with 5% (stress by nutritional deficit) or 10% fetal bovine serum (FBS). The cells were exposed to different laser doses from a near infrared diode laser prototype designed to provide a uniform irradiation of the wells. The experimental groups were: G1: 1.5 J/cm² + 5% FBS; G2: 1.5 J/cm² + 10% FBS; G3: 5 J/cm² + 5% FBS; G4: 5 J/cm² + 10% FBS; G5: 19 J/cm² + 5% FBS; G6: 19 J/cm² + 10% FBS. LLLT was performed in 3 consecutive irradiation cycles with a 24-hour interval. Non-irradiated cells cultured in DMEM supplemented with either 5 or 10% FBS served as control groups. The analysis of the metabolic response was performed by the MTT assay 3 h after the last irradiation. G1 presented an increase in SDH enzyme activity and differed significantly (Mann-Whitney test, p < 0.05) from the other groups. Analysis by scanning electron microscopy showed normal cell morphology in all groups. Under the tested conditions, LLLT stimulated the metabolic activity of MDPC-23 cultured in DMEM supplemented with 5% FBS and exposed to a laser dose of 1.5 J/cm². These findings are relevant for further studies on the action of near infrared lasers on cells with odontoblast phenotype.     

Conformational behavior of cis-2-methoxy, cis-2-methylthio, and cis-2-methylselenocyclohexanol: a theoretical and experimental investigation

Studies on the conformational equilibria of 2-methoxy, 2-methylthio, and 2-methylselenocyclohexanol are reported. Dynamic NMR spectroscopy experiments at 203-210 K were performed, which provided the percentages of each conformer in equilibrium. Theoretical calculations using the B3LYP method and aug-cc-pvdz basis set were applied to determine the differences in energy between the conformers. The analysis of the potential energy surface of each conformer showed the presence of two rotamers. Natural bond orbital analysis provided an explanation of which factors are driving the rotamer and conformer preferences.     

Credit contagion in a network of firms with spatial interaction

This contribution studies the effects of credit contagion on the credit risk of a portfolio of bank loans. To this aim we introduce a model that takes into account the counterparty risk in a network of interdependent firms that describes the presence of business relations among different firms. The location of the firms is simulated with probabilities computed using an entropy spatial interaction model. By means of a wide simulation analysis we investigate the behavior of the model proposed and study the effects of default contagion on the loss distribution of a portfolio of bank loans.     

Ant colony optimization for the arc routing problem with intermediate facilities under capacity and length restrictions

The aim of this paper is to introduce a new ant colony optimization procedure for the Arc Routing Problem with Intermediate Facilities under Capacity and Length Restrictions (CLARPIF), a variant of the Capacitated Arc Routing Problem (CARP) and of the Capacitated Arc Routing Problem with Intermediate Facilities (CARPIF). Computational results show that this algorithm is capable of providing substantial improvements over other known heuristics.     

Separation routine and extended formulations for the stable set problem in claw-free graphs

Mathematical Programming - The maximum weighted stable set problem in claw-free graphs is a well-known generalization of the maximum weighted matching problem, and a classical problem in...     

Microbiological control and antibacterial action of a propolis-containing mouthwash and control of dental plaque in humans

Propolis is a bee product with several biological properties. This study aimed at investigating a propolis-containing mouthwash, its organoleptic properties, microbial contamination and its antibacterial action in vitro. This mouthwash was assessed in vivo to control dental plaque in humans. The presence of microorganisms was analyzed and the minimum inhibitory concentration against Streptococcus mutans was determined. A comparative study was done in vivo using propolis, chlorhexidine, and propolis plus chlorhexidine in lower concentrations for 14 days. Dental plaque was analyzed by the Patient Hygiene Performance (PHP) index. The odontological product was yellow, cloudy, free of microbial contamination, and exerted an inhibitory action in vitro. Individuals who used a propolis-containing mouthwash for 14 consecutive days in combination or not to chlorhexidine showed a similar PHP index to chlorhexidine alone. The product exerted an antibacterial action in vitro and in vivo, exhibiting a positive action in the control of dental plaque.     

Polyfunctionalized pyrrolidines by Ugi multicomponent reaction followed by palladium-mediated SN2' cyclizations

A 4-component Ugi reaction with a suitable isocyanide, followed by a novel secondary transformation involving a Pd(II)-mediated (R5 = H) or a Pd(0)-mediated (R5 = CO2Me) SN2' cyclization to give highly functionalized N-acyl-2-vinylpyrrolidines, is reported. The overall yields are usually good and in most cases the Pd(0)-catalyzed reaction gave the final product in almost quantitative yield.     

A saturation phenomenon for a nonlinear nonlocal eigenvalue problem

Given \(1\le q \le 2\) and \(\alpha \in \mathbb {R}\), we study the properties of the solutions of the minimum problem

$$\begin{aligned} \lambda (\alpha ,q)=\min \left\{ \dfrac{\displaystyle \int _{-1}^{1}|u'|^{2}dx+\alpha \left| \int _{-1}^{1}|u|^{q-1}u\, dx\right| ^{\frac{2}{q}}}{\displaystyle \int _{-1}^{1}|u|^{2}dx}, u\in H_{0}^{1}(-1,1),\,u\not \equiv 0\right\} . \end{aligned}$$

In particular, depending on \(\alpha \) and q, we show that the minimizers have constant sign up to a critical value of \(\alpha =\alpha _{q}\), and when \(\alpha >\alpha _{q}\) the minimizers are odd.