Tunable Device for Long Focusing in the Sub-THz Frequency Range Based on Fresnel Mirrors.

THz radiation has gained great importance due to its potential applications in a wide variety of fields. For this reason, continuous efforts have been made to develop technological tools for use in this versatile band of the electromagnetic spectrum. Here, we propose a reflecting device with long focusing performances in the sub-THz band, using a bimirror device in which the relative angle is mechanically adjusted with the displacement of one of the mirrors. Despite the simplicity of the setup, the performance of this device is satisfactory down to a frequency of 0.1 THz. Theory and experience confirm that the bimirror is capable of focusing 0.1 THz radiation with a 2× magnification of the maximum input intensity while maintaining a longitudinal full width at half maximum (FWHM) of about 6 mm, which is about 12 times the depth of focus of a cylindrical optical element of the same focal length. In the absence of suitable THz equipment, the invariance property of the Fresnel diffraction integral allowed the predicted behavior to be tested in the THz range using conventional equipment operating at visible frequencies.

Long-Focusing Device for Broadband THz Applications Based on a Tunable Reflective Biprism.

THz radiation has assumed great importance thanks to the efforts in the development of technological tools used in this versatile band of the electromagnetic spectrum. Here, we propose a reflective biprism device with wavelength-independent long-focusing performances in the THz band by exploiting the high thermo-mechanical deformation of the elastomer polydimethylsiloxane (PDMS). This deformation allows for achieving significant optical path modulations in the THz band and effective focusing. The surface of a PDMS layer is covered with a gold thin film acting as a heater thanks to its absorption of wavelengths below ~500 nm. An invariance property of the Fresnel integral has been exploited to experimentally verify the THz performances of the device with an ordinary visible laser source, finding excellent agreement with the theoretical predictions at 1 and 3 THz. The same property also allowed us to experimentally verify that the reflective biprism focus has a longitudinal extension much greater than that exhibited by a benchmark convex cylindrical mirror with the same optical power. The device is thermo-mechanically stable up to a heating power of 270 mW, although it might be potentially exploited at higher powers with minor degradation of the optical performances.

Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling.

BACKGROUND: In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the "amoeboid angiogenesis" in the absence of proteases activity. METHODS: We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. RESULTS: Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesn't boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. CONCLUSIONS: We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

Threshold switching in nickel-doped zinc oxide based memristor for artificial sensory applications.

Electronic devices featuring biomimetic behaviour as electronic synapses and neurons have motivated the emergence of a new era in information and humanoid robotics technologies. In the human body, a nociceptor is a unique sensory neuron receptor that is capable of detecting harmful signals, leading to the central nervous system initiating a motor response. Herein, a nickel-doped zinc oxide (NZO)/Au based memristor is fabricated for the first time and characterized for artificial nociceptor application. For this, the introduction of a nickel-doped zinc oxide (NZO) layer between P++-Si and Au electrodes is used to eliminate the surface effects of the NZO layer, resulting in improved volatile threshold switching performance. Depending on the intensity, duration, and repetition rate of the external stimuli, this newly created memristor exhibits various critical nociceptive functions, including threshold, relaxation, allodynia, and hyperalgesia. The electron trapping/detrapping to/from the traps in the NZO layer is responsible for these nociceptive properties. This kind of NZO-based device produces a multifunctional nociceptor performance that is essential for applications in artificial intelligence systems, such as neural integrated devices with nanometer-sized features.

Room temperature dilute magnetic semiconductor response in (Gd, Co) co-doped ZnO for efficient spintronics applications.

The co-precipitation approach was utilized to experimentally synthesize ZnO, Zn0.96Gd0.04O and Zn0.96-x Gd0.04Co x O (Co = 0, 0.01, 0.03, 0.04) diluted magnetic semiconductor nanotubes. The influence of gadolinium and cobalt doping on the microstructure, morphology, and optical characteristics of ZnO was investigated, and the Gd doping and Co co-doping of the host ZnO was verified by XRD and EDX. The structural investigation revealed that the addition of gadolinium and cobalt to ZnO reduced crystallinity while maintaining the preferred orientation. The SEM study uncovered that the gadolinium and cobalt dopants did not affect the morphology of the produced nanotubes, which is further confirmed through TEM. In the UV-vis spectra, no defect-related absorption peaks were found. By raising the co-doping content, the crystalline phase of the doped samples was enhanced. It was discovered that the dielectric response and the a.c. electrical conductivity display a significant dependent relationship. With the decreasing frequency and increasing Co co-dopant concentration, the ε r and ε'' values decreased. It was also discovered that the ε r, ε'', and a.c. electrical conductivity increased when doping was present. Above room temperature, co-doped ZnO nanotubes exhibited ferromagnetic properties. The ferromagnetic behaviour increased as Gd (0.03) doping increased. Increasing the Co content decreased the ferromagnetic behaviour. It was observed that Zn0.96-x Gd0.04Co x O (x = 0.03) nanotubes exhibit superior electrical conductivity, magnetic and dielectric characteristics compared to pure ZnO. This high ferromagnetism is typically a result of a magnetic semiconductor that has been diluted. In addition, these nanoparticles are utilized to design spintronic-based applications in the form of thin-films.

Thermooptical PDMS-Single-Layer Graphene Axicon-like Device for Tunable Submicron Long Focus Beams.

Submicron long focusing range beams are gaining attention due to their potential applications, such as in optical manipulation, high-resolution lithography and microscopy. Here, we report on the theoretical and experimental characterization of an elastomeric polydimethylsiloxane/single layer graphene (PDMS/SLG) axicon-like tunable device, able to generate diffraction-resistant submicrometric spots in a pump and probe configuration. The working principle is based on the phase change of an input Gaussian beam induced in the elastomer via the thermo-optical effect, while the heating power is produced by the optical absorption of the SLG. The phase-modified beam is transformed by an objective into a long focus with submicron diameter. Our foci reach an experimental full width at half maximum (FWHM) spot diameter of 0.59 µm at the wavelength of 405 nm, with the FWHM length of the focal line greater than 90 µm. Moreover, the length of the focal line and the diameter of the focus can be easily tuned by varying the pump power. The proposed thermo-optical device can thus be useful for the simple and cheap improvement of the spatial resolution on long focus lines.

Diluted magnetic semiconductor properties in TM doped ZnO nanoparticles.

The hydrothermal method was used to create dilute magnetic semiconductor nanoparticles of Zn1-x Co x O (x = 0, 0.01, 0.05, 0.09). The effect of cobalt doping on the microstructure, morphological and optical properties of Zn1-x Co x O was also studied and the Co doping to host ZnO was confirmed from XRD and EDX analysis. The structural analysis showed that doping of cobalt into ZnO decreased the crystallinity, but the preferred orientation didn't change. SEM analysis revealed that the cobalt dopant did not have a strong influence on the shape of the synthesized nanoparticles. No defect-related absorption peaks were observed in the UV-Vis spectra. The crystallinity of the doped samples was improved by high growth temperature and long growth time. Ferromagnetic behavior above room temperature was detected in co-doped ZnO nanoparticles. The ferromagnetic behavior increased with increasing Co (up to x = 0.05) doping. The ferromagnetic behavior declined when the Co content was further increased. Related research shows that doped ZnO nanoparticles have better dielectric, electrical conductivity, and magnetic properties than pure ZnO. This high ferromagnetism is usually a response reported for dilute magnetic semiconductors. These semiconductor nanoparticles were further used to designed spintronic based applications.

Enhanced Antitumoral Activity and Photoacoustic Imaging Properties of AuNP-Enriched Endothelial Colony Forming Cells on Melanoma.

Near infrared (NIR)-resonant gold nanoparticles (AuNPs) hold great promise in cancer diagnostics and treatment. However, translating the theranostic potential of AuNPs into clinical applications still remains a challenge due to the difficulty to improve the efficiency and specificity of tumor delivery in vivo as well as the clearance from liver and spleen to avoid off target toxicity. In this study, endothelial colony forming cells (ECFCs) are exploited as vehicles to deliver AuNPs to tumors. It is first demonstrated that ECFCs display a great capability to intake AuNPs without losing viability, and exert antitumor activity per se. Using a human melanoma xenograft mouse model, it is next demonstrated that AuNP-loaded ECFCs retain their capacity to migrate to tumor sites in vivo 1 day after injection and stay in the tumor mass for more than 1 week. In addition, it is demonstrated that ECFC-loaded AuNPs are efficiently cleared by the liver over time and do not elicit any sign of damage to healthy tissue.

Dielectric-Loaded Waveguides as Advanced Platforms for Diagnostics and Application of Transparent Thin Films.

An alternative approach to classical surface plasmon resonance spectroscopy is dielectric-loaded waveguide (DLWG) spectroscopy, widely used in the past decades to investigate bio-interaction kinetics. Despite their wide application, a successful and clear approach to use the DLWGs for the one-step simultaneous determination of both the thickness and refractive index of organic thin films is absent in the literature. We propose here, for the first time, an experimental protocol based on the multimodal nature of DLWGs to be followed in order to evaluate the optical constants and thickness of transparent thin films with a unique measurement. The proposed method is general and can be applied to every class of transparent organic materials, with a resolution and accuracy which depend on the nature of the external medium (gaseous or liquid), the geometrical characteristics of the DLWG, and the values of both the thickness and dielectric constant of the thin film. From the experimental point of view, the method is demonstrated in a nitrogen environment with an accuracy of about 3%, for the special case of electroluminescent thin films of Eu3+ß-diketonate complexes, with an average thickness of about 20 nm. The high value of the refractive index measured for the thin film with the Eu(btfa)3(t-bpete) complex was confirmed by the use of a spectroscopic model based on the Judd-Ofelt theory, in which the magnetic dipole transition 5D0 → 7F1 (Eu3+) for similar films containing Eu3+ complexes is taken as a reference. The DLWGs are finally applied to control the refractive index changes of the organic thin films under UVA irradiation, with potential applications in dosimetry and monitoring light-induced transformation in organic thin films.

Cell-Mediated Release of Nanoparticles as a Preferential Option for Future Treatment of Melanoma.

Targeted and immune therapies have unquestionably improved the prognosis of melanoma patients. However the treatment of this neoplasm still requires approaches with a higher therapeutic index, in order to reduce shortcomings related to toxic effects and aspecific targeting. This means developing therapeutic tools derived with high affinity molecules for tumor components differentially expressed in melanoma cells with respect to their normal counterpart. Nanomedicine has sought to address this problem owing to the high modulability of nanoparticles. This approach exploits not only the enhanced permeability and retention effect typical of the tumor microenvironment (passive targeting), but also the use of specific "molecular antennas" that recognize some tumor-overexpressed molecules (active targeting). This line of research has given rise to the so-called "smart nanoparticles," some of which have already passed the preclinical phase and are under clinical trials in melanoma patients. To further improve nanoparticles partition within tumors, for some years now a line of thought is exploiting the molecular systems that regulate the innate tumor-homing activity of platelets, granulocytes, monocytes/macrophages, stem cells, endothelial-colony-forming cells, and red blood cells loaded with nanoparticles. This new vision springs from the results obtained with some of these cells in regenerative medicine, an approach called "cell therapy." This review takes into consideration the advantages of cell therapy as the only one capable of overcoming the limits of targeting imposed by the increased interstitial pressure of tumors.

Scanning Magnetic Microscope Using a Gradiometric Configuration for Characterization of Rock Samples.

Scanning magnetic microscopy is a tool that has been used to map magnetic fields with good spatial resolution and field sensitivity. This technology has great advantages over other instruments; for example, its operation does not require cryogenic technology, which reduces its operational cost and complexity. Here, we presented a spatial domain technique based on an equivalent layer approach for processing the data set produced by magnetic microscopy. This approach estimated a magnetic moment distribution over a fictitious layer composed by a set of dipoles located below the observation plane. For this purpose, we formulated a linear inverse problem for calculating the magnetic vector and its amplitude. Vector field maps are valuable tools for the magnetic interpretation of samples with a high spatial variability of magnetization. These maps could provide comprehensive information regarding the spatial distribution of magnetic carriers. In addition, this approach might be useful for characterizing isolated areas over samples or investigating the spatial magnetization distribution of bulk samples at the micro and millimeter scales. This technique could be useful for many applications that require samples that need to be mapped without a magnetic field at room temperature, including rock magnetism.

Two-color surface plasmon resonance nanosizer for gold nanoparticles.

We study the potentialities of a two-color Surface Plasmon Resonance (SPR) spectroscopy nanosizer by monitoring the assembling of a colloidal dispersion of citrate stabilized gold nanoparticles (AuNPs) on SiO2 surface. When the AuNPs/water composite's optical density layer is negligible and the electron mean-free path limitation is taken into account in the AuNPs' dielectric constant;s formulation, the surface density σ of the nanoparticle array and the statistical mean size of the nanoparticles can be straightly determined by using two-color SPR spectroscopy in the context of Maxwell's Garnett theory. The optical method, demonstrated experimentally for AuNPs with a nominal mean diameter of 15 nm, can, theoretically, be extended to bigger nanoparticles, based on a simple scaling relation between the extinction cross section of the single nanoparticle σext and the surface density σ. The experimental results, comparable to those obtained by AFM, transmission electron microscopy and dynamic light scattering technique, establish a novel insight on the SPR spectroscopy's potential to accurately characterize nanomaterials.

Limits of the Effective Medium Theory in Particle Amplified Surface Plasmon Resonance Spectroscopy Biosensors.

The resonant wave modes in monomodal and multimodal planar Surface Plasmon Resonance (SPR) sensors and their response to a bidimensional array of gold nanoparticles (AuNPs) are analyzed both theoretically and experimentally, to investigate the parameters that rule the correct nanoparticle counting in the emerging metal nanoparticle-amplified surface plasmon resonance (PA-SPR) spectroscopy. With numerical simulations based on the Finite Element Method (FEM), we evaluate the error performed in the determination of the surface density of nanoparticles σ when the Maxwell-Garnett effective medium theory is used for fast data processing of the SPR reflectivity curves upon nanoparticle detection. The deviation increases directly with the manifestations of non-negligible scattering cross-section of the single nanoparticle, dipole-dipole interactions between adjacent AuNPs and dipolar interactions with the metal substrate. Near field simulations show clearly the set-up of dipolar interactions when the dielectric thickness is smaller than 10 nm and confirm that the anomalous dispersion usually observed experimentally is due to the failure of the effective medium theories. Using citrate stabilized AuNPs with a nominal diameter of about 15 nm, we demonstrate experimentally that Dielectric Loaded Waveguides (DLWGs) can be used as accurate nanocounters in the range of surface density between 20 and 200 NP/µm², opening the way to the use of PA-SPR spectroscopy on systems mimicking the physiological cell membranes on SiO2 supports.

Lipid rafts: integrated platforms for vascular organization offering therapeutic opportunities.

Research on the nanoscale membrane structures known as lipid rafts is relevant to the fields of cancer biology, inflammation and ischaemia. Lipid rafts recruit molecules critical to signalling and regulation of the invasion process in malignant cells, the leukocytes that provide immunity in inflammation and the endothelial cells that build blood and lymphatic vessels, as well as the patterning of neural networks. As angiogenesis is a common denominator, regulation of receptors and signalling molecules critical to angiogenesis is central to the design of new approaches aimed at reducing, promoting or normalizing the angiogenic process. The goal of this review is to highlight some of the key issues that indicate the involvement of endothelial cell lipid rafts at each step of so-called 'sprouting angiogenesis', from stimulation of the vascular endothelial growth factor to the choice of tip cells, activation of migratory and invasion pathways, recruitment of molecules that guide axons in vascular patterning and maturation of blood vessels. Finally, the review addresses opportunities for future studies to define how these lipid domains (and their constituents) may be manipulated to stimulate the so-called 'normalization' of vascular networks within tumors, and be identified as the main target, enabling the development of more efficient chemotherapeutics and cancer immunotherapies.

Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis.

Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis.

Surface-enhanced fluorescence and surface-enhanced Raman scattering of push-pull molecules: sulfur-functionalized 4-amino-7-nitrobenzofurazan adsorbed on Ag and Au nanostructured substrates.

We investigated the chemisorption of self-assembled monolayers of sulfur-functionalized 4-amino-7-nitrobenzofurazan on gold and silver nanoisland films (NIFs) by means of surface-enhanced fluorescence (SEF) and surface-enhanced Raman scattering (SERS). The ligand is a push-pull molecule, where an intramolecular charge transfer occurs between an electron-donor and an electron-acceptor group, thus exhibiting nonlinear optical properties that are related to both SERS and SEF effects. The presence of different heteroatoms in the molecule ensures the possibility of chemical interaction with both silver and gold substrates. The SERS spectra suggest that furazan is bound to silver via lone pairs of the nitrogen atoms, whereas the ligand is linked to gold via a sulfur atom. Silver NIFs provide more efficient enhancement of both fluorescence and Raman scattering in comparison with gold NIFs. The present SEF and SERS investigation could provide useful information for foreseeing changes in the nonlinear responses of this push-pull molecule.

Förster resonance energy transfer (FRET) with a donor-acceptor system adsorbed on silver or gold nanoisland films.

We observed Förster resonance energy transfer (FRET) with a covalently linked donor-acceptor pair D-A consisting of two naphthalene groups acting as the donors and a benzofurazan group acting as the acceptor and adsorbed onto Ag or Au nanoisland films. The use of metal nanoisland films, which caused a strong enhancement of the Raman signal, permitted description of the adsorption mechanism onto the two metals. The intense fluorescence response of molecular adsorbates and the different behavior of the antenna on Ag and Au nanoislands are partly explained in terms of the radiating plasmon model.