Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and beta 1 integrin

Squamous cell carcinoma is a prevalent head and neck tumor with high mortality. We studied the role played by laminin alpha 1 chain peptide AG73 on migration, invasion, and protease activity of cells (OSCC) from human oral squamous cell carcinoma. Immunohistochemistry and immunofluorescence analyzed expression of laminin alpha 1 chain and MMP9 in oral squamous cells carcinoma in vivo and in vitro. Migratory activity of AG73-treated OSCC cells was investigated by monolayer wound assays and in chemotaxis chambers. AG73-induced invasion was assessed in Boyden chambers. Invasion depends on MMPs. Conditioned media from cells grown on AG73 was subjected to zymography. We searched for AG73 receptors related to these activities in OSCC cells. Immunofluorescence analyzed AG73induced colocalization of syndecan-1 and beta 1 integrin. Cells had these receptors silenced by siRNA, followed by treatment with AG73 and analysis of migration, invasion, and protease activity. Oral squamous cell carcinoma expresses laminin alpha 1 chain and MMP9. OSCC cells treated with AG73 showed increased migration, invasion, and protease activity. AG73 induced colocalization of syndecan-1 and beta 1 integrin. Knockdown of these receptors decreased AG73-dependent migration, invasion, and protease activity. Syndecan-1 and beta 1 integrin signaling downstream of AG73 regulate migration, invasion, and MMP production by OSCC cells.

BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients

Tumor necrosis factor-related apoptosis-inducing ligand-TNFSF10 (TRAIL), a member of the TNF-alpha family and a death receptor ligand, was shown to selectively kill tumor cells. Not surprisingly, TRAIL is downregulated in a variety of tumor cells, including BCR-ABL-positive leukemia. Although we know much about the molecular basis of TRAIL-mediated cell killing, the mechanism responsible for TRAIL inhibition in tumors remains elusive because (a) TRAIL can be regulated by retinoic acid (RA); (b) the tumor antigen preferentially expressed antigen of melanoma (PRAME) was shown to inhibit transcription of RA receptor target genes through the polycomb protein, enhancer of zeste homolog 2 (EZH2); and (c) we have found that TRAIL is inversely correlated with BCR-ABL in chronic myeloid leukemia (CML) patients. Thus, we decided to investigate the association of PRAME, EZH2 and TRAIL in BCR-ABL-positive leukemia. Here, we demonstrate that PRAME, but not EZH2, is upregulated in BCR-ABL cells and is associated with the progression of disease in CML patients. There is a positive correlation between PRAME and BCR-ABL and an inverse correlation between PRAME and TRAIL in these patients. Importantly, knocking down PRAME or EZH2 by RNA interference in a BCR-ABL-positive cell line restores TRAIL expression. Moreover, there is an enrichment of EZH2 binding on the promoter region of TRAIL in a CML cell line. This binding is lost after PRAME knockdown. Finally, knocking down PRAME or EZH2, and consequently induction of TRAIL expression, enhances Imatinib sensibility. Taken together, our data reveal a novel regulatory mechanism responsible for lowering TRAIL expression and provide the basis of alternative targets for combined therapeutic strategies for CML. Oncogene (2011) 30, 223-233; doi:10.1038/onc.2010.409; published online 13 September 2010

Evaluation of laccases and melanization in clinical and environmental Cryptococcus neoformans samples by non-denaturing PAGE

The increased incidence of infections caused by the opportunistic pathogen Cryptococcus neoformans, which mainly affects immunocompromised patients but can also infect immunocompetent individuals, has needed additional studies on this micro-organism`s pathogenicity and factors related to virulence, such as enzyme production, for a better understanding of the aetiology of cryptococcosis. The aim of this study was to verify the applicability of non-denaturing PAGE for analysis of laccases by quantification of the amount of melanin pigment produced by clinical and environmental strains of C. neoformans. After incubation of the gel with the substrate L-dopa, strains produced melanin spots of a bright brown to black colour. Quantification of these spots was performed by densitometry analysis and the amount of melanin produced was calculated and compared among the strains. All strains showed laccase activity. Serotype B strains showed a higher melanin intensity than serotype A strains. Over half of the clinical strains (56.2%) showed the lowest melanin intensities, suggesting that melanin production may not be the main virulence factor against host defence. The clinical strain ICB 88 revealed two melanin spots on the gel, indicating the presence of two laccase isoforms. The environmental strains showed the highest values of melanin intensity, which may be related to previous exposure to environmental stress conditions.

Eugenol modifies the excitability of rat sciatic nerve and superior cervical ganglion neurons

Eugenol is a phenylpropene obtained from the essential oils of plants such as clove and basil which has ample use in dentistry. Eugenol possesses analgesic effects that may be related to the inhibition of voltage-dependent Na(+) channels and/or to the activation of TRPV1 receptors or both. In the present study, electrophysiological parameters were taken from the compound action potentials of the isolated rat sciatic nerve and from neurons of the superior cervical ganglion (SCG) impaled with sharp microelectrodes under current-clamp conditions. In the isolated rat sciatic nerve, eugenol inhibited the compound action potential in a concentration-dependent manner. Action potentials recorded from SCG neurons were inhibited by eugenol with an IC(50) of 0.31 mM. At high concentrations (2 mM), during brief applications. eugenol caused significant action potential blockade while it did not interfere with the resting membrane potential or the membrane input resistance. Surprisingly, however, at low eugenol concentrations (0.6 mM), during long time applications, a reversible reduction (by about 50%) in the input membrane resistance was observed, suggesting the possible involvement of a secondary delayed effect of eugenol to reduce neuronal excitability. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Use of Information Visualization Methods Eliminating Cross Talk in Multiple Sensing Units Investigated for a Light-Addressable Potentiometric Sensor

The integration of nanostructured films containing biomolecules and silicon-based technologies is a promising direction for reaching miniaturized biosensors that exhibit high sensitivity and selectivity. A challenge, however, is to avoid cross talk among sensing units in an array with multiple sensors located on a small area. In this letter, we describe an array of 16 sensing units, of a light-addressable potentiometric sensor (LAPS), which was made with layer-by-Layer (LbL) films of a poly(amidomine) dendrimer (PAMAM) and single-walled carbon nanotubes (SWNTs), coated with a layer of the enzyme penicillinase. A visual inspection of the data from constant-current measurements with liquid samples containing distinct concentrations of penicillin, glucose, or a buffer indicated a possible cross talk between units that contained penicillinase and those that did not. With the use of multidimensional data projection techniques, normally employed in information Visualization methods, we managed to distinguish the results from the modified LAPS, even in cases where the units were adjacent to each other. Furthermore, the plots generated with the interactive document map (IDMAP) projection technique enabled the distinction of the different concentrations of penicillin, from 5 mmol L(-1) down to 0.5 mmol L(-1). Data visualization also confirmed the enhanced performance of the sensing units containing carbon nanotubes, consistent with the analysis of results for LAPS sensors. The use of visual analytics, as with projection methods, may be essential to handle a large amount of data generated in multiple sensor arrays to achieve high performance in miniaturized systems.

Comparing machine learning classifiers in potential distribution modelling

Species` potential distribution modelling consists of building a representation of the fundamental ecological requirements of a species from biotic and abiotic conditions where the species is known to occur. Such models can be valuable tools to understand the biogeography of species and to support the prediction of its presence/absence considering a particular environment scenario. This paper investigates the use of different supervised machine learning techniques to model the potential distribution of 35 plant species from Latin America. Each technique was able to extract a different representation of the relations between the environmental conditions and the distribution profile of the species. The experimental results highlight the good performance of random trees classifiers, indicating this particular technique as a promising candidate for modelling species` potential distribution. (C) 2010 Elsevier Ltd. All rights reserved.

Template-based quadrilateral meshing

Generating quadrilateral meshes is a highly non-trivial task, as design decisions are frequently driven by specific application demands. Automatic techniques can optimize objective quality metrics, such as mesh regularity, orthogonality, alignment and adaptivity; however, they cannot make subjective design decisions. There are a few quad meshing approaches that offer some mechanisms to include the user in the mesh generation process; however, these techniques either require a large amount of user interaction or do not provide necessary or easy to use inputs. Here, we propose a template-based approach for generating quad-only meshes from triangle surfaces. Our approach offers a flexible mechanism to allow external input, through the definition of alignment features that are respected during the mesh generation process. While allowing user inputs to support subjective design decisions, our approach also takes into account objective quality metrics to produce semi-regular, quad-only meshes that align well to desired surface features. Published by Elsevier Ltd.

Template-based quadrilateral mesh generation from imaging data

This paper describes a novel template-based meshing approach for generating good quality quadrilateral meshes from 2D digital images. This approach builds upon an existing image-based mesh generation technique called Imeshp, which enables us to create a segmented triangle mesh from an image without the need for an image segmentation step. Our approach generates a quadrilateral mesh using an indirect scheme, which converts the segmented triangle mesh created by the initial steps of the Imesh technique into a quadrilateral one. The triangle-to-quadrilateral conversion makes use of template meshes of triangles. To ensure good element quality, the conversion step is followed by a smoothing step, which is based on a new optimization-based procedure. We show several examples of meshes generated by our approach, and present a thorough experimental evaluation of the quality of the meshes given as examples.

The decline of the world`s energy intensity

Energy intensity of the total primary energy supply (TPES), total final energy consumption (TFC) and LOSSES in the conversion from TPES to TFC were analyzed for the World, OECD and Rest of the World (ROW) countries. LOSSES increased significantly for all groups of countries due to the increase of electricity production from coal in the period studied (1971-2008). Electricity share final consumption almost doubled, increasing from 8.8% to 17.2% in the period studied. However the energy intensity of LOSSES remained practically constant, which reflects the fact that the efficiency of electricity generation from coal (the main source of electricity) remained practically constant in that period. Despite the attractiveness of end-use devices running on electricity such as computers, which is typical of modern societies, the CO(2) emissions are bound to increase unless coal is replaced by less carbon emitting sources such as natural gas, renewables and nuclear energy. (C) 2011 Elsevier Ltd. All rights reserved.

Numerical analysis of an incremented statistical sampling procedure in MCNP

MCNP has stood so far as one of the main Monte Carlo radiation transport codes. Its use, as any other Monte Carlo based code, has increased as computers perform calculations faster and become more affordable along time. However, the use of Monte Carlo method to tally events in volumes which represent a small fraction of the whole system may turn to be unfeasible, if a straight analogue transport procedure (no use of variance reduction techniques) is employed and precise results are demanded. Calculations of reaction rates in activation foils placed in critical systems turn to be one of the mentioned cases. The present work takes advantage of the fixed source representation from MCNP to perform the above mentioned task in a more effective sampling way (characterizing neutron population in the vicinity of the tallying region and using it in a geometric reduced coupled simulation). An extended analysis of source dependent parameters is studied in order to understand their influence on simulation performance and on validity of results. Although discrepant results have been observed for small enveloping regions, the procedure presents itself as very efficient, giving adequate and precise results in shorter times than the standard analogue procedure. (C) 2007 Elsevier Ltd. All rights reserved.

EPR, FT-IR and XRD investigation of soils from Parana, Brazil

Samples of Araucaria area soil from Parana state, Brazil, were separated by particle size fractionation and investigated by electron paramagnetic resonance (EPR) in X-Band of 9.5 GHz at room temperature and 77K, infra-red spectroscopy and X-ray diffractometry. The paramagnetic species in the soil samples were identified by comparison with EPR spectra of some minerals studied recently by our group, several soil types and/or soil components investigated in the literature. The value of g = 2.1 (Delta H = 85 mT) indicated the presence of ferrihydrite. Hematite was identified by g = 2.1 (Delta H = 100 mT) and g = 4.3 for Fe(3+) lines of the concentrated dominium and diluted dominium. Kaolinite was identified by IR and EPR with the resonance at g = 4.3 attributed to Fe(3+) ions in isolated sites of tetrahedral and octahedral symmetry with rhombic distortion. The resonances at g = 3.7 and g = 4.9 were attributed to Fe(3+) in more highly symmetrical environment than rhombic symmetry, but not in axial symmetry. Three signals around g = 2 were attributed to radiation defects, plus additional resonances at g = 2.8 and 9.0. Signals less intense than those at g = 2.1, 3.7, and 6.5, observed for clear grains of soil, were attributed to presence of Fe(3+) in quartz which was identified by IR and XDR. (C) 2011 Elsevier B.V. All rights reserved.

Projectile breakup dynamics for (6)Li+(59)Co: Kinematical analysis of alpha-d coincidences

A study of the kinematics of the alpha-d coincidences in the (6)Li + (59)Co system at a bombarding energy of E(lab) = 29.6MeV is presented. With exclusive measurements performed over different angular intervals it is possible to identify the respective contributions of the sequential and direct projectile breakup components. The angular distributions of both breakup components are fairly well described by the Continuum-Discretized Coupled-Channels framework (CDCC). Furthermore, a careful analysis of these processes using a semiclassical approach provides information on both their lifetime and their distance of occurrence with respect to the target. Breakup to the low-lying (near-threshold) continuum is delayed, and happens at large internuclear distances. This suggests that the influence of the projectile breakup on the complete fusion process can be related essentially to the direct breakup to the (6)Li high-lying continuum spectrum.

(6)Li direct breakup lifetimes

alpha-d coincidence data are studied for the (6)Li + (59)Co reaction at E(lab) = 29.6 MeV. A kinematic analysis is used to identify which process, leading to the same final state, has the major contribution for selected angular regions. The contributions of the (6)Li sequential and direct breakup to the incomplete fusion/transfer process is discussed by considering the corresponding lifetimes obtained by using a semiclassical approach.

Absolute normalization for uncorrelated background with the event mixing technique

We present a method to determine the magnitude of the uncorrelated background distribution obtained with the event mixing technique, through the simultaneous observation of the projectile elastic scattering in different detectors, which correspond to random coincidences. The procedure is tested with alpha-d angular correlation data from the (6)Li + (59)Co reaction at E(lab) = 29.6 MeV. We also show that the method can be applied using the product of singles events, when singles measurements are available. (C) 2009 Elsevier B.V. All rights reserved.

Associating biosensing properties with the morphological structure of multilayers containing carbon nanotubes on field-effect devices

The control of molecular architecture provided by the layer-by-layer (LbL) technique has led to enhanced biosensors, in which advantageous features of distinct materials can be combined. Full optimization of biosensing performance, however, is only reached if the film morphology is suitable for the principle of detection of a specific biosensor. In this paper, we report a detailed morphology analysis of LbL films made with alternating layers of single-walled carbon nanotubes (SWNTs) and polyamidoamine (PAMAM) dendrimers, which were then covered with a layer of penicillinase (PEN). An optimized performance to detect penicillin G was obtained with 6-bilayer SWNT/PAMAM LbL films deposited on p-Si-SiO(2)-Ta(2)O(5) chips, used in biosensors based on a capacitive electrolyte-insulator-semiconductor (EIS) and a light-addressable potentiometric sensor (LAPS) structure, respectively. Field-emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) images indicated that the LbL films were porous, with a large surface area due to interconnection of SWNT into PAMAM layers. This morphology was instrumental for the adsorption of a larger quantity of PEN, with the resulting LbL film being highly stable. The experiments to detect penicillin were performed with constant-capacitance (Con Cap) and constant-current (CC) measurements for EIS and LAPS sensors, respectively, which revealed an enhanced detection signal and sensitivity of ca. 100 mV/decade for the field-effect sensors modified with the PAMAM/SWNT LbL film. It is concluded that controlling film morphology is essential for an enhanced performance of biosensors, not only in terms of sensitivity but also stability and response time. (C) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim