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This paper focuses on numerical strategies to predict the behavior of piezoelectric materials and devices characterized by heterogenous microstructural features. Several of these materials are attractive for technological applications including mechanical energy harvesting and pressure/force sensors. After a general introduction on the linear piezoelastic problem, two multiscale strategies are presented and applied to the solution of simple but significant problems frequently encountered in nanotechnology test setups. The first strategy consists in classical homogenization based on the choice of a representative volume element and on the classical micro-macro work equality known as Hill’s lemma. The second strategy is based on the so called FE2 method, where the microscale average response resulting from an homogenization procedure is directly used as a constitutive model at each quadrature point at the macroscale. Both strategies have been implemented within an advanced numeric framework based on the authomatic differentiation technique.

In recent years it has been hypothesized that cancer stem cells (CSCs) are the actual driving force of tumor formation, highlighting the need to specifically target CSCs to successfully eradicate cancer growth and recurrence. Particularly, the deregulation of physiological signaling pathways controlling stem cell proliferation, self-renewal, differentiation, and metabolism is currently considered as one of the leading determinants of cancer formation. Given their peculiar, slow-dividing phenotype and their ability to respond to multiple microenvironmental stimuli, stem cells appear to be more susceptible to genetic and epigenetic carcinogens, possibly undergoing mutations resulting in tumor formation. In particular, some animal-derived bioactive nutrients and metabolites known to affect the hormonal milieu, and also chemicals derived from food processing and cooking, have been described as possible carcinogenic factors. Here, we review most recent literature in this field, highlighting how some environmental toxicants, some specific nutrients and their secondary products can induce carcinogenesis, possibly impacting stem cells and their niches, thus causing tumor growth. © Mary Ann Liebert, Inc. 2015.

In this Full Paper, the possibility of reversibly changing the diffraction efficiency of gratings, fabricated by soft molding lithography on polymer films, containing photochromic molecules, is demonstrated. In particular, alternating UV and visible laser irradiation of the gratings causes the doped photochromic molecules to undergo transformations, which induce reversible dimensional changes to the samples. As a result, reversible changes are monitored in the intensity of the beams of a diode laser, transmitted and diffracted from the gratings. These changes affect the diffraction efficiency, which is increased upon irradiation with UV and decreased after irradiation with visible laser light. Such gratings are promising candidates for the fabrication of modern optical components such as optical switching devices.

We report on the wettability properties of silicon surfaces, simultaneously structured on the micrometre-scale and the nanometre-scale by femtosecond (fs) laser irradiation to render silicon hydrophobic. By varying the laser fluence, it was possible to control the wetting properties of a silicon surface through a systematic and reproducible variation of the surface roughness. In particular, the silicon - water contact angle could be increased from 66 degrees to more than 130 degrees. Such behaviour is described by incomplete liquid penetration within the silicon features, still leaving partially trapped air inside. We also show how controllable design and tailoring of the surface microstructures by wettability gradients can drive the motion of the drop's centre of mass towards a desired direction ( even upwards).

Realizing active, light-emitting fibers made of conjugated polymers by the electrospinning method is generally challenging. Electrospinning of plasma-treated conjugated polymer solutions is here developed for the production of light-emitting microfibers and nanofibers. Active fibers from conjugated polymer solutions rapidly processed by a cold atmospheric argon plasma are electrospun in an effective way, and they show a smoother surface and bead-less morphology, as well as preserved optical properties in terms of absorption, emission, and photoluminescence quantum yield. In addition, the polarization of emitted light and more notably photon waveguiding along the length of individual fibers are remarkably enhanced by electrospinning plasma-treated solutions. These properties come from a synergetic combination of favorable intermolecular coupling in the solutions, increased order of macromolecules on the nanoscale, and resulting fiber morphology. Such findings make the coupling of the electrospinning method and cold atmospheric plasma processing on conjugated polymer solutions a highly promising and possibly general route to generate light-emitting and conductive micro- and nanostructures for organic photonics and electronics.

Radio frequency (RF) signals propagate through most materials that we are surrounded by while light is blocked by many of these materials. This feature makes wireless networks based on light (which are also referred to as LiFi networks) inherently more secure. However, it can also lead to sudden link failure if the legitimate data link is blocked because of user movements or changes in device orientation. In this paper, the secrecy capacity has been analysed with the consideration of imperfect channel state information, random device orientation and probability of link blockage for the case of a single eavesdropper. It has been found that the secrecy capacity almost doubles in a standing activity as opposed to a sitting activity and that the density of blocking objects degrades the secrecy capacity in single access point networks. It is evident that environmental factors and user behaviour have a significant impact on the secrecy performance and, thus, need to be considered for robust physical layer security (PLS) design in LiFi networks.

International audience; (M.M.) † These authors contributed equally to this work. Abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite the progress of new treatments, the risk of recurrence, morbidity, and death remains significant and the long-term adverse effects in survivors are substantial. The fraction of cancer stem-like cells (CSCs) because of their self-renewal ability and multi-lineage differentiation potential is critical for tumor initiation, growth, and resistance to therapies. For the development of new CSC-targeted therapies, further in-depth studies are needed using enriched and stable MB-CSCs populations. This work, aimed at identifying the amount of CSCs in three available human cell lines (DAOY, D341, and D283), describes different approaches based on the expression of stemness markers. First, we explored potential differences in gene and protein expression patterns of specific stem cell markers. Then, in order to identify and discriminate undifferentiated from differentiated cells, MB cells were characterized using a physical characterization method based on a high-frequency dielectrophoresis approach. Finally, we compared their tumorigenic potential in vivo, through engrafting in nude mice. Concordantly, our findings identified the D283 human cell line as an ideal model of CSCs, providing important evidence on the use of a commercial human MB cell line for the development of new strategic CSC-targeting therapies.

We report on the investigation of the influence of the molecular packing and film morphology on the field-effect charge mobility in 2,3-thienoimide-based oligothiophenes semiconductors (Cn-NT4N). Organic field-effect transistors are realized by implementing both vacuum and solution methods in order to control the solid-state phase of the active layer. Thermal sublimation in a high vacuum chamber and supersonic molecular beam deposition were used as vacuum-based fabrication approaches for preparing thin films, while lithographically controlled wetting was used, as a solution-deposition technique, for the fabrication of the microstructured films. Thermal sublimation leads to thin films with a phase packing showing ambipolar behaviour, while supersonic molecular beam deposition enables, by varying the deposition rate, the formation of two different crystal phases, showing ambipolar and unipolar field-effect behaviours. On the other hand, lithographically controlled wetting enables the formation of Cn-NT4N microstructured active layers and their implementation in field-effect transistors.

We report on a comprehensive study of the unique adhesive properties of mats of polymethylmethacrylate (PMMA) nanofibers produced by electrospinning. Fibers are deposited on glass, varying the diameter and the relative orientation of the polymer filaments (random vs aligned configuration). While no significant variation is observed in the static contact angle (about 130{\deg}) of deposited water drops upon changing the average fiber diameter up to the micrometer scale, fibers are found to exhibit unequalled water adhesion. Placed vertically, they can hold up water drops as large as 60 microL, more than twice the values typically obtained with hairy surfaces prepared by different methods. For aligned fibers with anisotropic wetting behavior, the maximum volume measured in the direction perpendicular to the fibers goes up to 90 {\mu}L. This work suggests new routes to tailor the wetting behavior on extended areas by nanofiber coatings, with possible applications in adsorbing and catalytic surfaces, microfluidic devices, and filtration technologies., Comment: 17 pages, 5 figures, 2 tables

Random optical media (ROM) are a novel class of photonic materials characterized by a disordered assembly of the elementary constituents (such as particles, wires and fibers), that determines unique scattering, absorption and emission properties. The propagation of light in ROM is affected by the size and optical properties (refractive index, absorption and emission wavelengths) of their components, as well as by the overall 3-dimensional architecture. So far, most of the investigated ROM have been realized using liquid dispersions or bulk samples embedding colloidal nanoparticles or porous systems. While nanowire-based ROM are poorly investigated, such materials can feature new optical effects related to the elongated shape of their building blocks and to their light-transport properties. Here we report on the fabrication and on the morphological and spectroscopic characterization of hybrid organic-inorganic nanowires, realized by doping polymers with dielectric nanoparticles. We investigate light diffusion and multi-scattering properties of 3- dimensional ROM formed by organic and hybrid nanowires, as well as field localization in 2-dimensional networks. The influence of nanowire geometry and composition on the scattering properties is also discussed.

Active nanowires and nanofibers can be realized by the electric-field induced stretching of polymer solutions with sufficient molecular entanglements. The resulting nanomaterials are attracting an increasing attention in view of their application in a wide variety of fields, including optoelectronics, photonics, energy harvesting, nanoelectronics, and microelectromechanical systems. Realizing nanocomposite nanofibers is especially interesting in this respect. In particular, methods suitable for embedding inorganic nanocrystals in electrified jets and then in active fiber systems allow for controlling light-scattering and refractive index properties in the realized fibrous materials. We here report on the design, realization, and morphological and spectroscopic characterization of new species of active, composite nanowires and nanofibers for nanophotonics. We focus on the properties of light-confinement and photon transport along the nanowire longitudinal axis, and on how these depend on nanoparticle incorporation. Optical losses mechanisms and their influence on device design and performances are also presented and discussed., Comment: 7 pages, 3 figures, 29 references. Invited contribution. Copyright (2016) Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited

Hypoxia Inducible Factor (HIF)-2? protein expression in solid tumors promotes stem-like phenotype in cancer stem cells and increases tumorigenic potential in non-stem cancer cells. Recently, we have shown HIF-1/2? gene expression is correlated to neuroblastoma (NB) poor survival and to undifferentiated tumor state; HIF-2? protein was demonstrated to enhance aggressive features of the disease. In this study, we used proteomic experiments on NB cells to investigate HIF-2? downstream-regulated proteins and/or pathways with the aim of providing novel therapeutic targets and/or bad prognosis markers. We verified that pathways mostly altered by HIF-2? perturbation are involved in tumor progression. In particular, HIF-2? induces alteration of central metabolism and splicing control pathways. Simultaneously, WNT, RAS/MAPK and PI3K/AKT activity and/or expression are affected and may impact on the sensitivity and the intensity of HIF-2?-regulated pathways. Furthermore, genes coding the identified HIF-2?-related markers built a signature able to stratify NB patients with unfavorable outcome. Taken together, our findings underline the relevance of dissecting the downstream effects of a poor survival marker in developing targeted therapy and improving patient stratification. Future prospective studies are needed to translate the use of these data into the clinical practice.

Electrospinning technologies for the realization of active polymeric nanomaterials can be easily up-scaled, opening perspectives to industrial exploitation, and due to their versatility they can be employed to finely tailor the size, morphology and macroscopic assembly of fibers as well as their functional properties. Light-emitting or other active polymer nanofibers, made of conjugated polymers or of blends embedding chromophores or other functional dopants, are suitable for various applications in advanced photonics and sensing technologies. In particular, their almost one-dimensional geometry and finely tunable composition make them interesting materials for developing novel lasing devices. However, electrospinning techniques rely on a large variety of parameters and possible experimental geometries, and they need to be carefully optimized in order to obtain suitable topographical and photonic properties in the resulting nanostructures. Targeted features include smooth and uniform fiber surface, dimensional control, as well as filament alignment, enhanced light emission, and stimulated emission. We here present various optimization strategies for electrospinning methods which have been implemented and developed by us for the realization of lasing architectures based on polymer nanofibers. The geometry of the resulting nanowires leads to peculiar light-scattering from spun filaments, and to controllable lasing characteristics., Comment: Comments: 7 pages, 4 figures, 20 references. Invited contribution. Copyright (2016) Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited

The chemokine receptor CXCR4 plays a central role in organ-specific homing and tumor spreading and is induced by hypoxia. B lymphocytes are exposed to low oxygen tensions during their development, but the influence of hypoxia on their physiology is poorly understood. Here, we show that hypoxia is associated with up-regulation of CXCR4 expression in human normal and malignant B cells, through both transcriptional and posttranslational mechanisms. However, a dichotomic functional response to CXCR4 triggering was observed: both peripheral B cells and lymphomas arising from mature B cells displayed increased responses to CXCR4 triggering under hypoxia, whereas germinal center (GC) B cells as well as GC-derived lymphomas showed CXCR4 receptor desensitization. This phenomenon was associated with differential modulation of key signal-transducing molecules, including mitogen-activated protein kinase phosphatase-1 and regulator of G protein signaling molecule-1. The unresponsiveness of GC-derived lymphomatous B cells to CXCR4 triggering under hypoxia may have implications for the development and pathogenesis of GC-derived lymphoid tumors. [Cancer Res 2007;67(18):8605–14]

Anti-VEGF therapy perturbs tumor metabolism, severely impairing oxygen, glucose, and ATP levels. In this study, we investigated the effects of anti-VEGF therapy in multiple experimental tumor models that differ in their glycolytic phenotypes to gain insights into optimal modulation of the metabolic features of this therapy. Prolonged treatments induced vascular regression and necrosis in tumor xenograft models, with highly glycolytic tumors becoming treatment resistant more rapidly than poorly glycolytic tumors. By PET imaging, prolonged treatments yielded an increase in both hypoxic and proliferative regions of tumors. A selection for highly glycolytic cells was noted and this metabolic shift was stable and associated with increased tumor aggressiveness and resistance to VEGF blockade in serially transplanted mice. Our results support the hypothesis that the highly glycolytic phenotype of tumor cells studied in xenograft models, either primary or secondary, is a cell-autonomous trait conferring resistance to VEGF blockade. The finding that metabolic traits of tumors can be selected by antiangiogenic therapy suggests insights into the evolutionary dynamics of tumor metabolism. Cancer Res; 75(1); 120–33. ©2014 AACR.

The nanopatterning of light-emitting molecular crystals with semiconducting properties can be crucial for the development of future optoelectronic and nanoelectronic devices based on organic materials. In this respect, electron-beam writing is a powerful tool to realize patterns at the nanoscale, but it is still rarely applied to active organic materials. Here, sub-100-nm-scale nanopatterning is performed on the surface of quaterthiophene monocrystals by direct maskless electron-beam writing. Gratings are produced on organic crystals with periods ranging from 80 nm to 1 μm and single-line lateral dimensions ranging from 20 to 500 nm, with electron-beam exposure doses between 100 and 1500 μC/cm2. The morphological and texturing properties of the pattern are discussed, together with the interaction mechanisms between the electron beam and the crystal. The resulting modulation of the light emission is consistent with Bragg scattering from the patterned periodic features. © 2014 American Chemical Society.

The Notch ligand DII4 has a recognized role during both physiologic and tumor angiogenesis, as it contributes to regulate Notch activity in endothelial cells (EC). The effects of DII4 on Notch signaling in tumor cells expressing Notch receptors remain, however, largely unknown. Here, we report that escape of human T-cell acute lymphoblastic leukemia (T-ALL) cells or colorectal cancer cells from dormancy is associated with DII4 expression in the tumor microenvironment and increased Notch3 signaling in tumor cells. DII4 was expressed at early time points during the angiogenic process, and its expression preceded perfusion of the newly established vessels. Treatment of EC with angiogenic factors induced DII4 expression and increased Notch3 activation in cocultured T-ALL cells. Neutralization of DII4 greatly reduced EC-mediated activation of Notch 3 signaling in T-ALL cells and blocked tumorigenesis. Moreover, silencing Notch3 by RNA interference had marked antiproliferative and proapoptotic effects on T-ALL cells in vitro and reduced tumorigenicity in vivo. Our results elucidate a novel mechanism by which a direct interplay between endothelial and tumor cells promotes survival and triggers tumor growth. [Cancer Res 2009;69(4):1314-23] The Notch ligand DII4 has a recognized role during both physiologic and tumor angiogenesis, as it contributes to regulate Notch activity in endothelial cells (EC). The effects of DII4 on Notch signaling in tumor cells expressing Notch receptors remain, however, largely unknown. Here, we report that escape of human T-cell acute lymphoblastic leukemia (T-ALL) cells or colorectal cancer cells from dormancy is associated with DII4 expression in the tumor microenvironment and increased Notch3 signaling in tumor cells. DII4 was expressed at early time points during the angiogenic process, and its expression preceded perfusion of the newly established vessels. Treatment of EC with angiogenic factors induced DII4 expression and increased Notch3 activation in cocultured T-ALL cells. Neutralization of DII4 greatly reduced EC-mediated activation of Notch 3 signaling in T-ALL cells and blocked tumorigenesis. Moreover, silencing Notch3 by RNA interference had marked antiproliferative and proapoptotic effects on T-ALL cells in vitro and reduced tumorigenicity in vivo. Our results elucidate a novel mechanism by which a direct interplay between endothelial and tumor cells promotes survival and triggers tumor growth. [Cancer Res 2009;69(4):1314-23]

The authors report on monolithic, light-emitting vertical microcavities based on an organic semiconductor single crystal. The devices are realized by reactive electron-beam deposition of dielectric mirrors and growth of tetracene crystals by physical vapor transport. The microcavities exhibit optical cavity modes in the visible range (550-580 nm) with full width at half maximum down to 2-3 nm, corresponding to a Q factor of about 200, and polarization-induced modal splitting up to 20 meV. These results open perspectives for the realization of polarized-emitting optoelectronic devices based on organic crystals. (c) 2008 American Institute of Physics.

The authors demonstrate direct electron-beam writing on conjugated polymers as patterning route to realize plastic optoelectronic devices. Lithography was carried out by a 20 kV electron beam dose in the range of 0-360 mu C/cm(2), with no need for masking or development/etching processes. The features could be employed for the fabrication of polymer distributed feedback lasers, exhibiting optically pumped lasing in the range of 607-620 nm, with a spectral linewidth around 1 nm and a threshold excitation fluence of 34 mu J/cm(2). (c) 2007 American Institute of Physics.