Undrained expansion of a cylindrical cavity in clays with fabric anisotropy: theoretical solution

This paper presents a novel, exact, semi-analytical solution for the quasi-static undrained expansion of a cylindrical cavity in soft soils with fabric anisotropy. This is the first theoretical solution of the undrained expansion of a cylindrical cavity under plane strain conditions for soft soils with anisotropic behaviour of plastic nature. The solution is rigorously developed in detail, introducing a new stress invariant to deal with the soil fabric. The semianalytical solution requires numerical evaluation of a system of six first-order ordinary differential equations. The results agree with finite element analyses and show the influence of anisotropic plastic behaviour. The effective stresses at critical state are constant, and they may be analytically related to the undrained shear strength. The initial vertical cross-anisotropy caused by soil deposition changes towards a radial cross-anisotropy after cavity expansion. The analysis of the stress paths shows that proper modelling of anisotropic plastic behaviour involves modelling not only the initial fabric anisotropy but also its evolution with plastic straining.The research was initiated as part of GEO-INSTALL (Modelling Installation Effects in Geotechnical Engineering, PIAP-GA-2009-230638) and CREEP (Creep of Geomaterials, PIAP-GA-2011-286397) projects supported by the European Community through the programme Marie Curie Industry-Academia Partnerships and Pathways (IAPP) under the 7th Framework Programme

Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. Canine hypodense MHC class II-CD5-CD21-CD11b+ cells can be subdivided into polymorphonuclear (CADO48A+CD14-) and monocytic (CADO48A-CD14+) MDSC subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct, and moreover reveal a statistically significant similarity between canine and previously published human PMN-MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly higher in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < 0.001; M-MDSCs: p < 0.01). By leveraging the power of evolution, we also identified additional conserved genes in PMN-MDSCs of multiple species that may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer

Analysis of the interaction of substituted coumarins with DPPH free radical by means of multivariate statistics

The interaction of some substituted coumarin derivatives with the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical was analysed by means of multivariate statistics using a variety of molecular descriptors. The compounds contain a conjugated double bond system, which was considered to be an essential structural characteristic for the free-radical scavenging activity. Partial least-square analysis led to an adequate two-component model based on bulk descriptors and the electronic properties concerning atoms involved or next to the double-bond systems. © 2004 The Authors Recieved

Different retention behavior of structurally diverse basic and neutral drugs in immobilized artificial membrane and reversed-phase high performance liquid chromatography: Comparison with octanol-water partitioning

The retention behavior of 43 structurally diverse neutral and basic drugs in immobilized artificial membrane chromatography was investigated and compared to the reversed-phase retention and octanol-water partitioning. IAM chromatography was performed using morpholinepropanesulfonic acid (MOPS) or phosphate buffer saline (PBS) at pH 7.4 as the aqueous component of the mobile phase. The differences in the retention factors were attributed to increased electrostatic interactions in the MOPS environment, dependent on the fraction of charged species. Electrostatic interactions were found to play a key role in the relationships with reversed-phase retention factors determined under two different mobile phase conditions as well as in the relationships with lipophilicity data. IAM retention factors correlated better with octanol-water partition coefficients log P than with log D7.4, as a result of the contribution of electrostatic forces in IAM retention. With log D7.4 the relationships were improved when the fraction of charged species was taken into consideration. In any case the regression coefficient of log P or log D7.4 was considerably lower than 1 reflecting the reduced hydrophobic environment of the IAM stationary phase. The different data sets were submitted to principal component analysis for further exploration of their similarities/dissimilarities. © 2006 Elsevier B.V. All rights reserved

Retention of substituted coumarins using immobilized artificial membrane (IAM) chromatography: A comparative study with n-octanol partitioning and reversed-phase HPLC and TLC

The chromatographic indices log kwIAM have been determined by HPLC on an immobilized artificial membrane column for a set of coumarin derivatives. The investigated compounds contain substituted amidoximes, or substituted heterocycles directly attached to the coumarinic skeleton. The log kwIAM values were compared to previously reported data of octanol-water partition coefficients and extrapolated capacity factors determined by reversed phase HPLC and TLC. The log kwIAM values of the investigated compounds were found to be comparable with the corresponding log P values, although they constitute a lower lipophilicity scale due to the reduced hydrophobic environment of the IAM stationary phase. These features were exemplified in their interrelationship with a slope close to unity and a large negative intercept. In contrast their comparison with the corresponding HPLC and RP-TLC capacity factors revealed differences in the retention mechanism reflected in slopes lower than unity, which were postulated to be due to secondary interactions under the reversed phase chromatographic conditions. However, conformational effects in the molecular structures of the coumarin derivatives were found to have a similar impact in their affinity for the IAM and octadecyl silane stationary phases, while they did not affect their octanol-water partitioning. © 2005 Elsevier B.V. All rights reserved

Electrostatic interactions and ionization effect in immobilized artificial membrane retention. A comparative study with octanol-water partitioning

The present study is a continuation of our efforts to investigate the effect of electrostatic interactions and ionization on immobilized artificial membrane (IAM) retention. The previous set of neutral and basic drugs was extended to include acids and ampholytes and analogous buffer conditions in the mobile phase were used, namely morpholinepropanesulfonic acid and phosphate buffer saline, adjusted at pH 7.4. The important contribution of electrostatic forces in IAM retention of positively charged species was further justified by the results of the present study, while analogous electrostatic interactions for ionized acidic drugs were not found to affect significantly the affinity for the IAM stationary phase. The critical role of shielding or exposure of the charged centers on the IAM surface, as a result of the effect of the aqueous component of the mobile phase, was evaluated by the use of water instead of buffer for a number of drugs. Measurements at pH 5.0 demonstrated the effect of ionization in IAM retention despite the partial compensation by electrostatic interactions in the case of protonated basic drugs. Silanophilic interactions were also found to play a potential role as secondary interactions in IAM retention. IAM chromatographic indices were compared to octanol-water distribution coefficients and the corresponding relationships established. Finally, solvation analysis was applied in the aim to gain insight in the balance of forces between IAM retention and octanol-water partitioning. The results showed that apart from electrostatic interactions, there is no significant differentiation between the two systems. © 2008 Elsevier B.V. All rights reserved

Investigation of the relationships between logP and various chromatographic indices for a series of substituted coumarins. Evaluation of their similarity/dissimilarity using multivariate statistics

High Performance Liquid Chromatography and Reversed Phase Thin Layer Chromatography were applied in a series of substituted coumarins, in the aim to evaluate the conformity of the retention data with octanol water partition coefficients. The investigated compounds contain substituted amidoximes, or substituted heterocycles directly attached to the coumarinic skeleton. The interrelationships between the extrapolated capacity factors logkw and RMw, the corresponding slopes SHPLC, STLC and the Chromatographic Indices φoHPLC. φoTLC, as well as their correlation with logP were established. Conformation effects, concerning particularly molecules with planar structures, were found to interfere in retention, leading to deviations from the partition mechanism in both RP-TLC and HPLC. Moreover, HPLC appeared to be more sensitive to secondary effects in retention. The similarities/dissimilarities between logP and the various chromatographic indices at a more fundamental molecular level were further investigated by means of multivariate data analysis using calculated molecular descriptors. © 2005 WILEY-VCH Verlag GmbH &amp;amp; Co. KGaA

Modelling of aldose reductase inhibitory activity of pyrrol-1-yl-acetic acid derivatives by means of multivariate statistics.

The inhibition of the aldose reductase enzyme (AR) is considered to be a promising approach to control chronic diabetes complications as well as a number of other pathological conditions. Thus considerable efforts are devoted to the development of aldose reductase inhibitors (ARIs) as possible pharmacotherapeutic agents. The establishment of adequate QSAR models would serve to this purpose. In the present study multivariate statistics was applied in order to analyse the AR inhibitory activity data of twenty three pyrrol-1-yl-acetic acid derivatives on the basis of essential molecular descriptors. The compounds contain one or two carbonyl keto groups, which serve as a bridge to link the pyrrole moiety to aromatic nuclei with or without further substitution. An adequate one component model with satisfactory statistics was obtained and validated for its robustness and predictive ability. The influence of the different descriptors in ARI activity is discussed. The derived model was further used to predict the activity of four independent compounds and the contribution of their specific structural characteristics in ARI activity was evaluated