The Interplay between HGF/c-met Axis and Nox4 in BRAF Mutated Melanoma

Background: Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have a role in the development and progression of melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor (HGF)/c-met axis is emerging as a critical player because it can play a role in drug resistance. Indeed, 50% of melanoma patients present BRAF mutations, however, all responders develop resistance to the inhibitors typically within one year of treatment. Interestingly, BRAF inhibitors induce reactive oxygen species (ROS) in melanoma cells, therefore, the aim of this study was to investigate a possible interplay between HGF/c-met and ROS sources, such as NADPH oxidases (Nox). Methods: The expression of c-met and Nox were quantified in 60 patients with primary cutaneous melanoma. In vitro experiments on melanoma primary cells and the cell line were performed to dissect the underpinned molecular mechanism. Results: The outcome of interest was the correlation between the high positivity for both Nox4 and c-met and metastasis occurring at least 1 year later than melanoma diagnosis in BRAF mutated patients, in contrast to nonmutated. In vitro experiments demonstrated that the axis HGF/c-met/Nox4/ROS triggers the epithelial-mesenchymal transition. Conclusions: The observed correlation suggests an interplay between c-met and Nox4 in promoting the onset of metastasis. This study suggests that Nox4 inhibitors could be associated to the current therapy used to treat melanoma patients with BRAF mutations.     

Spatial choice behaviour: logit models and neural network analysis

Neural networks are becoming popular analysis tools in spatial research, as is witnessed by various applications in recent years. The performance of neural network analysis needs to be carefully judged, however, since the theoretical underpinning of neuro-computing is still weakly enveloped. In the present paper we will use the logit model as a benchmark for evaluating the result of neural network models, based on an empirical case study from Italy. The present paper aims to assess the foreseeable impact of the high-speed train in Italy, by investigating competition effects between rail and road transport modes. Two statistical models will then be compared, viz. the traditional logit model and a new technique for information processing, viz. the feedforward neural network model. In the study two different cases – corresponding to a different set of attributes – are investigated, namely by using only ‘time’ attributes and by using both ‘time’ and ‘cost’ attributes. From an economic viewpoint, both models appear to highlight the advantage of introducing the high-speed train system in that they show high probabilities of choosing the improved rail transport mode. The feedforward neural net model seems to provide reasonable predictions compared to those obtained by means of a logit model. An important lesson however, is that it is important to define properly the neural network architecture and to train sufficiently the network during the learning phase. Received: June 1996 / Accepted: February 1997     

Discordance Rate of HER2 Status in Primary Gastric Carcinomas and Synchronous Lymph Node Metastases: A Multicenter Retrospective Analysis

Background: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. Materials and Methods: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. Results: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. Conclusions: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.     

Synthesis and characterization of polyurethane cationomer/MMT hybrid composite

BACKGROUND: The development of polymeric nanocomposites incorporating intercalated or exfoliated layered silicate clays into the organic matrix has been substantially motivated by the significant improvements induced by the presence of the inorganic component. Moreover, understanding and controlling the dispersion of inorganic layers into segmented polyurethane matrices by means of ionic interactions, and exploiting these interactions to enhance physicomechanical behaviour, could be of great interest in the field of polymer nanocomposites. RESULTS: New cationic polyurethane elastomers were prepared starting from poly(butylene adipate)diol (M_n = 1000 g mol^?1), 4,4′‐diphenylmethane diisocyanate, 1,4‐butanediol and N‐methyldiethanolamine or N,N′‐β‐hydroxyethylpiperazine, used as potential quaternizable moieties. The characterization of the polymers was achieved using specific analyses employed for the macromolecular samples (Fourier transform infrared and ¹H NMR spectroscopy, thermogravimetric analysis (TGA), gel permeation chromatography). An extension of our research on polymers reinforced with organically modified montmorillonite (OM‐MMT) in order to prepare hybrid composites with improved properties was performed and the resulting materials were characterized using TGA, X‐ray diffraction, atomic force microscopy and scanning electron microscopy. Also, the mechanical properties of the cationic polyurethane/OM‐MMT composites were investigated in comparison with the pristine ionic/non‐ionic polymers and their composites containing non‐ionic polymer blended with OM‐MMT or ionic polymer and unmodified MMT. CONCLUSION: The insertion of the organically modified clay into the polymeric matrix gave an improvement of the mechanical properties of the polyurethane composites, especially the tensile strength and stiffness of the hybrid materials. Copyright © 2009 Society of Chemical Industry     

The role of creep and fatigue in determining the high-temperature behaviour of AISI H11 tempered steel for aluminium extrusion dies

The present study was aimed to analyze the effect of loading cycles on the behaviour of the AISI H11 tool steel commonly used for aluminium extrusion dies working at high temperatures and under high, cyclic stresses. A technological test method in which the specimen geometry resembled the mandrel of a hollow extrusion die was developed. Finite element analyses were performed to aid in determining specimen geometry and dimensions as well as the levels of stress to be applied to the specimen so as to replicate the conditions typically encountered by industrial hollow extrusion dies. Tests were performed on a Gleeble thermomechanical simulator by heating the specimen using Joule's effect and by applying loading for up to 6.30 h or till specimen failure. Displacements during the tests at 380, 490, 540 and 580 °C and under the average stresses of 400, 600 and 800 MPa were determined. The specimens were tested under creep (with the load held at a fixed value), fatigue (cyclic loading) and creep–fatigue (cyclic loading with a 3 min dwell-time) loading, thereby allowing a direct comparison between different deforming mechanisms. The results showed that the test could physically simulate the cyclic loading on the hollow die during aluminium extrusion and that the creep condition represented the most severe working condition. In addition, the tests could reveal the interaction between creep and fatigue mechanisms.     

A compact double-gate MOSFET model comprising quantum-mechanicaland nonstatic effects

In this work, we investigate the electrical properties of the Double-Gate MOSFET (DG-MOSFET), which turn out to be very promising for device miniaturization below 0.1 μm. A compact model which accounts for charge quantization within the channel, Fermi statistics, and nonstatic effects in the transport model is worked out. The main results of this investigation are: (1) the ideality factor in subthreshold is equal to unity, i.e., the slope of the turn-on characteristic is 60 mV/decade at room temperature; (2) the drain-induced barrier lowering is minimized by the shielding effect of the double gate, which allows us to reduce the channel length below 30 nm; and (3) the device transconductance per unit width is maximized by the combination of the double gate and by a strong velocity overshoot which occurs in response to the sudden variation of the electric field at the source end of the channel, and which can be further strengthened near the drain in view of the short device length. As a result, a sustained electron velocity of nearly twice the saturation velocity is achievable. The above results prove that the potential performance advantages of the double-gate device architecture may be worth the development effort     

Effect of itaconic acid on the wet scrub resistance of highly pigmented paints for architectural coatings

This study investigates the influence of carboxylic monomers, such as itaconic acid (IA), on the colloidal properties of the latexes made by semi-continuous emulsion copolymerization of styrene (STy) with n-butyl acrylate (BA). A number of copolymerization runs were carried out with different IA concentrations. The effect of functional monomer on the overall conversion, the colloidal properties of the latexes, and the distribution of the carboxylic groups (buried, particle surface and aqueous phase) were examined. The carboxylic groups present in the latexes were analyzed using conductimetric and potentiometric titrations. The behavior of the IA on the wet scrub resistance of highly pigmented paints for architectural coatings was examined and correlated with the distribution of the carboxylic groups. The results obtained showed that the properties of highly pigmented paints are greatly dependent on the amount and distribution of the carboxylic groups. The carboxylic acid distributed in the aqueous phase has a strong influence on the wet scrub resistance and on the characteristics of the final products.     

Some Polyamides,Polyesters, and Polyurethanes Containing AZO Groups

The paper discusses the synthesis of the N,N,′-azobis(formamidopropionic) acid (AFP), along with some characteristics determined from NMR spectrum, differential thermal analysis, and DSC. The behavior of AFP acid—as well as of its analogue, N,N′-azobis(formamidoacetic) acid (AFA)—has been studied in the reaction with aromatic diamine and with bis(glycol)terephthalate, leading to azopolymers of the azopolyamide, or azopolyester, type. On employing N,N′-bis(β-hydroxyethyl) azobis-formamide (HEAF) as the azo bifunctional compound in the reaction with diphenylmethane diisocyanate, a polyurethane possessing azo groups was obtained. The structure of the azopolymers has been spectroscopically confirmed.     

A simple model for the photocurrent density of a graded band gap CIGS thin film solar cell

A simple model for the photocurrent density of a linearly graded band gap Cu(In,Ga)Se₂ solar cell is presented. Both generation and recombination mechanisms in the space charge region and absorber region of the cell are considered. The carrier collection function and effective absorption coefficient are introduced in the calculations to obtain a more realistic model. The results show that photocurrent density of the graded band-gap solar cell is higher than that with a constant averaged band gap. There is an optimum for grading strength or band gap widening of the absorber region. Recombination current reduces the photocurrent density with a lower reduction in the absorber material than in the depletion region. For longer diffusion lengths (or greater values of carrier collection factor), a higher photocurrent density is obtained except where collection probability is already unity everywhere in the absorber.