Preliminary Evidence on the Diagnostic and Molecular Role of Circulating Soluble EGFR in Non-Small Cell Lung Cancer

Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies.     

Structure−Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents

Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.     

Modelling of effects of ultrastructural morphology on the hygroelastic properties of wood fibres

Wood fibres constitute the structural framework of e.g. wood, paper, board and composites, where stiffness and dimensional stability are of importance. An analytical modelling approach has been used for prediction of hygroelastic response, and assessment of the stresses in thick-walled cylinder models of wood fibres. A wood fibre was idealised as a multilayered hollow cylinder made of orthotropic material with helical orientation. The hygroelastic response of the layered assembly due to axisymmetric loading and moisture content changes was obtained by solving the corresponding boundary value problem of elasticity. A simple solution scheme based on the state space approach and the transfer matrix method was employed. This was combined with an analytical ultrastructural homogenisation method, used to link hygroelastic properties of constituent wood polymers to properties of each layer. Predicted hygroelastic response captured experimentally measured behaviour. Fibres that were constrained not to twist showed a stiffer response than fibres allowed twisting under uniaxial loading. It was also shown that the ultrastructure, i.e. the microfibril angle, will control the hygroexpansion in the same way as it controls the compliance of the cell wall. Qualitative failure trends comparable with experimental observations could be established with stress analysis and a simple plane-stress failure criterion.     

Polyimide foams from powder: Experimental analysis of competitive diffusion phenomena

In the present study, various diffusive processes have been investigated during foaming of powdered precursors of polyimide. A detailed analysis of the powdered precursor's characteristics allows for an enhanced morphological understanding of the resulting microstructures and foam unit cell. Parameters that are central to the foaming process such as particle morphology, volatile concentration and sorption-desorption processes are evaluated. Isothermal and non-isothermal desorption experiments have been carried out by thermogravimetric analysis (TGA), and specific diffusive processes have been correlated to thermodynamic and kinetic transitions by means of modulated differential scanning calorimetry (MDSC) of the corresponding materials. It was found that two primary fluxes of volatiles, one out of the external surface of the particles (responsible for volatile desorption) and the other into the growing bubble (responsible for vapor supersaturation inside the bubble) compete against each other creating a competitive scenario that becomes the controlling factor for potential inflation within the precursor particles.     

Stochastic molecular descriptors for polymers. 4. Study of complex mixtures with topological indices of mass spectra spiral and star networks: The blood proteome case

The Quantitative Structure-Property Relationships (QSPRs) based on Graph or Network Theory are important for predicting the properties of polymeric systems. In the three previous papers of this series (Polymer 45 (2004) 3845-3853; Polymer 46 (2005) 2791-2798; and Polymer 46 (2005) 6461-6473) we focused on the uses of molecular graph parameters called topological indices (TIs) to link the structure of polymers with their biological properties. However, there has been little effort to extend these TIs to the study of complex mixtures of artificial polymers or biopolymers such as nucleic acids and proteins. In this sense, Blood Proteome (BP) is one of the most important and complex mixtures containing protein polymers. For instance, outcomes obtained by Mass Spectrometry (MS) analysis of BP are very useful for the early detection of diseases and drug-induced toxicities. Here, we use two Spiral and Star Network representations of the MS outcomes and defined a new type of TIs. The new TIs introduced here are the spectral moments (π_k) of the stochastic matrix associated to the Spiral graph and describe non-linear relationships between the different regions of the MS characteristic of BP. We used the MARCH-INSIDE approach to calculate the π_k(SN) of different BP samples and S2SNet to determine several Star graph TIs. In the second step, we develop the corresponding Quantitative Proteome-Property Relationship (QPPR) models using the Linear Discriminant Analysis (LDA). QPPRs are the analogues of QSPRs in the case of complex biopolymer mixtures. Specifically, the new QPPRs derived here may be used to detect drug-induced cardiac toxicities from BP samples. Different Machine Learning classification algorithms were used to fit the QPPRs based on π_k(SN), showing J48 decision tree classifier to have the best performance. These results suggest that the present approach captures important features of the complex biopolymers mixtures and opens new opportunities to the application of the idea supporting classic QSPRs in polymer sciences.     

Vitamin D3 inhibits proliferation and increases c-myc expression in fibroblasts from psoriatic patients

Fibroblast cultures were established from the skin of normal and psoriatic subjects. The response to 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] of each kind of cells was assessed by measuring tritiated thymidine incorporation into DNA as an index of cell proliferation. We found that both types of cells responded with a similar dose- and time-dependent inhibition of thymidine incorporation. We also studied the response of the mRNA encoding the proto-oncogene c-myc, since its level is associated to the proliferative state in many cell types. Psoriatic fibroblasts contained higher basal amounts of c-myc RNA than control fibroblasts. Addition of 1,25-(OH)2D3 to the culture medium induced a time-dependent increase of c-myc RNA in psoriatic fibroblasts but not in controls. As a control, retinoic acid had no effect in any of the two cell types. It is concluded that in primary normal human fibroblasts, c-myc RNA levels are not correlated with the proliferative state, and that there is an altered expression of this proto-oncogene in psoriasis.     

A survey on approaches to gridification

The Grid shows itself as a globally distributed computing environment, in which hardware and software resources are virtualized to transparently provide applications with vast capabilities. Just like the electrical power grid, the Grid aims at offering a powerful yet easy‐to‐use computing infrastructure to which applications can be easily ‘plugged’ and efficiently executed. Unfortunately, it is still very difficult to Grid‐enable applications, since current tools force users to take into account many details when adapting applications to run on the Grid. In this paper, we survey some of the recent efforts in providing tools for easy gridification of applications and propose several taxonomies to identify approaches followed in the materialization of such tools. We conclude this paper by describing common features among the proposed approaches, and by pointing out open issues and future directions in the research and development of gridification methods. Copyright © 2007 John Wiley & Sons, Ltd.