Molecular Mechanism of Cannabinoids in Cancer Progression

Cannabinoids are a family of heterogeneous compounds that mostly interact with receptors eliciting several physiological effects both in the central and peripheral nervous systems and in peripheral organs. They exert anticancer action by modulating signaling pathways involved in cancer progression; furthermore, the effects induced by their use depend on both the type of tumor and their action on the components of the endocannabinoid system. This review will explore the mechanism of action of the cannabinoids in signaling pathways involved in cancer proliferation, neovascularisation, migration, invasion, metastasis, and tumor angiogenesis.     

Analysis of the novel flexure parallel micromanipulators based on multi-level displacement amplifier with/without symmetrical design

Conventional flexure-based parallel micromanipulators (FPM) usually suffer from a small stroke. The performance of a FPM is highly related to the stroke of each actuated limb and the associated constraints, including non-actuated joints. To conquer the drawbacks of the small workspace of conventional FPMs, a device for displacement amplification could improve motion ranges when incorporated into the design of the actuated limbs. This research is focused on the development of a group of unique FPMs with/without symmetrical design based on a multi-level displacement amplifier. Firstly, structural modeling based on a compact and modular design is introduced. Then a macro/micro analysis of the displacement amplifier is conducted. Subsequently, a comprehensive finite-element modeling including the strain and total deformation, modal and frequency response is undertaken to examine the mechanical behavior of the proposed mechanism. The developed method and technology provide a promising solution to enhance the performance of generic FPMs.     

Fermentative ability of alginate-prebiotic encapsulated Lactobacillus acidophilus and survival under simulated gastrointestinal conditions

Lactobacillus acidophilus was encapsulated in alginate-inulin-xanthan gum and its ability to grow in carrot juice and survive 8 weeks of storage at 4 °C and subsequent exposure to artificial gastrointestinal conditions were assessed. Encapsulation significantly enhanced cell viability after fermentation and storage (6 × 10¹² and 4 × 10¹⁰ cells/ml versus 4 × 10¹⁰ and 2 × 10⁸ for free cells, respectively). Encapsulation protected L. acidophilus from exposure to simulated gastric conditions; minor alterations in viability and the protein profile occurred after incubation in pancreatic juice. For free cells, viability decreased significantly and the expression of numerous proteins was lost after incubation in gastric and pancreatic juice. Thus, encapsulation preserved probiotic bacterial viability and activity; the addition of inulin as a prebiotic component could enhance the functional properties of food products containing this formulation.     

Density and localization of calcium channels of the L-type in human pulmonary artery

The pharmacological profile and the anatomical localization of Ca2+ channels of the L-type were investigated in the human pulmonary artery to identify possible mechanisms involved in the regulation of the pulmonary vascular tone. Analysis was performed on slide-mounted frozen sections of human pulmonary artery using radioligand binding assay techniques associated with light microscope autoradiography. [3H]-Nicardipine was used as ligand. Human renal and right coronary arteries also were used as systemic reference arteries. Binding of [3H]-nicardipine to sections of human pulmonary artery was time-, temperature- and concentration-dependent, saturable and reversible. In the human pulmonary artery, the apparent equilibrium dissociation constant (Kd) was 0.12+/-0.02 nM and the maximum density of binding sites (Bmax) was 38.15+/-2.25 fmol/mg tissue. Kd values were 0.3+/-0.01 nM and 0.5+/-0.02 in the human renal artery and right coronary artery respectively. Bmax values were 248+/-16 fmol/mg tissue and 173+/-9.5 fmol/mg tissue in the human renal artery and right coronary artery respectively. The pharmacological profile of [3H]-nicardipine binding to sections of human pulmonary artery was consistent with the labeling of Ca2+ channels of the L-type. It was similar in the pulmonary artery and in the human renal and right coronary arteries. Light microscope autoradiography revealed a high density of [3H]-nicardipine binding sites within smooth muscle of the tunica media of human pulmonary artery as well as of human renal and right coronary arteries. A lower accumulation of the radioligand occurred in the tunica adventitia. No specific binding was noticeable in the tunica intima. Our data suggest that human pulmonary artery expresses Ca2+ channels of the L-type sensitive to dihydropyridines. These sites have similar affinity and lower density than those expressed by systemic arteries. The presence of Ca2+ channels of the L-type in human pulmonary artery suggests that their pharmacological manipulation may be considered in the treatment of pulmonary hypertension.     

Study of α-radiation damage in a steel for fusion technology

The status of a joint ENEA-University of Ancona research programme concerning radiation damage analysis in materials for fusion technology is presented. Preliminary results of electron-microscopy observations are presented concerning the analysis of He-bubble coalescence in martensitic steel 1.4914 developed for the Next European Torus (NET) project, and some small-angle neutron scattering (SANS) measurements on non-irradiated reference samples of the same material are discussed.     

Modeling Web Applications by the Multiple Levels of Integrity Policy

We propose a formal method to validate the reliability of a web application, by modeling interactions among its constituent objects. Modeling exploits the recent “Multiple Levels of Integrity” mechanism which allows objects with dynamically changing reliability to cooperate within the application. The novelty of the method is the ability to describe systems where objects can modify their own integrity level, and react to such changes in other objects. The model is formalized with a process algebra, properties are expressed using the ACTL temporal logic, and can be verified by means of a model checker. Any instance of the above model inherits both the established properties and the proof techniques. To substantiate our proposal we consider several case-studies of web applications, showing how to express specific useful properties, and their validation schemata. Examples range from on-line travel agencies, inverted Turing test to detect malicious web-bots, to content cross-validation in peer to peer systems.     

Homocysteine Solution-Induced Response in Aerosol Jet Printed OECTs by Means of Gold and Platinum Gate Electrodes

Homocysteine (Hcy) is a non-protein, sulfur-containing amino acid, which is recognized as a possible risk factor for coronary artery and other pathologies when its levels in the blood exceed the normal range of between 5 and 12 μmol/L (hyperhomocysteinemia). At present, standard procedures in laboratory medicine, such as high-performance liquid chromatography (HPLC), are commonly employed for the quantitation of total Hcy (tHcy), i.e., the sum of the protein-bound (oxidized) and free (homocystine plus reduced Hcy) forms, in biological fluids (particularly, serum or plasma). Here, the response of Aerosol Jet-printed organic electrochemical transistors (OECTs), in the presence of either reduced (free) and oxidized Hcy-based solutions, was analyzed. Two different experimental protocols were followed to this end: the former consisting of gold (Au) electrodes’ biothiol-induced thiolation, while the latter simply used bare platinum (Pt) electrodes. Electrochemical impedance spectroscopy (EIS) analysis was performed both to validate the gold thiolation protocol and to gain insights into the reduced Hcy sensing mechanism by the Au-gated OECTs, which provided a final limit of detection (LoD) of 80 nM. For the OECT response based on Platinum gate electrodes, on the other hand, a LoD of 180 nM was found in the presence of albumin-bound Hcy, with this being the most abundant oxidized Hcy-form (i.e., the protein-bound form) in physiological fluids. Despite the lack of any biochemical functionalization supporting the response selectivity, the findings discussed in this work highlight the potential role of OECT in the development of low-cost point-of-care (POC) electronic platforms that are suitable for the evaluation, in humans, of Hcy levels within the physiological range and in cases of hyperhomocysteinemia.     

Photolithography by a tunable electro-optical lithium niobate phase array

Photolithography experiments are performed by means of an optical phase mask with electrooptically tunable phase step. The phase mask consists of a 2-dimensional hexagonal lattice of inverted ferroelectric domains fabricated on a z-cut lithium niobate substrate. The electro-optically tunable phase step, between inverted domain, is obtained by the application of an external electric field along the z axis of the crystal via transparent electrodes. The collimated beam of an argon laser passes through the phase mask and the near field intensity patterns, at different planes of the Talbot length and for different values of the applied voltage, are used for photolithographic experiments. Preliminary results are shown and further applications are discussed.