Lipid Cubic Mesophases Combined with Superparamagnetic Iron Oxide Nanoparticles: A Hybrid Multifunctional Platform with Tunable Magnetic Properties for Nanomedical Applications

Hybrid materials composed of superparamagnetic iron oxide nanoparticles (SPIONs) and lipid self-assemblies possess considerable applicative potential in the biomedical field, specifically, for drug/nutrient delivery. Recently, we showed that SPIONs-doped lipid cubic liquid crystals undergo a cubic-to-hexagonal phase transition under the action of temperature or of an alternating magnetic field (AMF). This transition triggers the release of drugs embedded in the lipid scaffold or in the water channels. In this contribution, we address this phenomenon in depth, to fully elucidate the structural details and optimize the design of hybrid multifunctional carriers for drug delivery. Combining small-angle X-ray scattering (SAXS) with a magnetic characterization, we find that, in bulk lipid cubic phases, the cubic-to-hexagonal transition determines the magnetic response of SPIONs. We then extend the investigation from bulk liquid-crystalline phases to colloidal dispersions, i.e., to lipid/SPIONs nanoparticles with cubic internal structure (“magnetocubosomes”). Through Synchrotron SAXS, we monitor the structural response of magnetocubosomes while exposed to an AMF: the magnetic energy, converted into heat by SPIONs, activates the cubic-to-hexagonal transition, and can thus be used as a remote stimulus to spike drug release “on-demand”. In addition, we show that the AMF-induced phase transition in magnetocubosomes steers the realignment of SPIONs into linear string assemblies and connect this effect with the change in their magnetic properties, observed at the bulk level. Finally, we assess the internalization ability and cytotoxicity of magnetocubosomes in vitro on HT29 adenocarcinoma cancer cells, in order to test the applicability of these smart carriers in drug delivery applications.     

In situ optical control and stabilization of the curing process of holographic gratings with a nematic film-polymer-slice sequence structure

We report on the realization of what we believe to be a new holographic setup for the fabrication of polymer liquid-crystal polymer-slice diffraction gratings, which utilizes an optical-feedback-driven nanopositioning technique. We have increased the stability of the interference pattern by means of a simple piezomirror used in a feedback configuration to keep constant the phase of the interferometer. The feedback system is driven by a proportional, integral, derivative control software, and the stability degree is controlled by the reference signal coming from a standard test grating. A preliminary experimental characterization indicates that good control and stabilization of parasitic fluctuations of the interference pattern are obtained.     

Microstructure and Nanoindentation Properties of Surface Textures Obtained by Laser Machining and Molding in Silicon Carbide

A surface texture consisting of an array of holes in SiC components was obtained by either conventional molding in the green state or post sintering laser machining. According to microstructural analysis, very regular holes were obtained by laser machining with minimal microstructural damage. Irregular holes with defects and voids were instead found for the surface textures obtained via molding. Nanoindentation tests were performed in the areas close to the holes and no significant alteration of the mechanical properties was found after laser machining.     

Progress in control and data acquisition for the ITER neutral beam test facility

SPIDER, the ion source test bed in the ITER neutral beam test facility, is under construction and its operation is expected to start in 2014. Control and data acquisition for SPIDER are undergoing final design. SPIDER CODAS, as the control and data acquisition system is referred to, is requested to manage 25 plant units, to acquire 1000 analogue signals with sampling rates ranging from a few S/s to 10 MS/s, to acquire images with up to 100 frames per second, to operate with long pulses lasting up to 1 h, and to sustain 200 MB/s data throughput into the data archive with an annual data storage amount of up to 50 TB. SPIDER CODAS software architecture integrates three open-source software frameworks each addressing specific system requirements. Slow control exploits the synergy among EPICS and Siemens S7 programmable controllers. Data handling is by MDSplus a data-centric framework that is geared towards the collection and organization of scientific data. Diagnostics based on imaging drive the design of data throughput and archive size. Fast control is implemented by using MARTe, a data-driven, object-oriented, real-time environment. The paper will describe in detail the progress of the system hardware and software architecture and will show how the software frameworks interact to provide the functions requested by SPIDER CODAS. The paper will focus on how the performance requirements can be met with the described SPIDER CODAS architecture, describing the progress achieved by carrying out prototyping activities.     

Synthesis and biological evaluation of isosteric analogues of FK866, an inhibitor of NAD salvage

One of the great challenges of medicinal chemistry is to create novel, effective, chemotherapeutic agents that show specificity for cancer cells combined with low systemic toxicity. A novel idea is to target the enzymes of the NAD biosynthesis and recycling pathways given that cancer cells display a higher NAD turnover rate than healthy cells. To this end, the compound FK866 (APO866; (E)-N-[4-(1-benzoylpiperidin-4-yl) butyl]-3-(pyridin-3-yl) acrylamide), which blocks nicotinamide phosphoribosyltransferase (NMPRTase) has entered clinical trials as a potential chemotherapeutic agent. Here we report the synthesis of analogues of FK866 synthesized by click chemistry.     

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: a multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1beta and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1beta and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal-Wallis analysis of variance with Dunn's multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences ( P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1beta determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface.     

A Virtual Instrument for the Measurement of IEEE Std. 1459-2000 Power Quantities

In this paper, the authors present a PC-based instrument for the measurement of electrical-power quantities defined in IEEE Std. 1459. The instrument is based on a time-domain technique for the detection of the fundamental and harmonic components of voltages and currents. The time-domain strategy was originally developed by the authors for three-phase, three-wire systems. In that paper, the strategy had been extended to both three-phase, four-wire and single-phase systems. Simulation tests were carried out to assess the uncertainty contribution of the proposed strategy in the absence of the measurement transducers. Moreover, the accuracy of the PC-based instrument with its transducers was evaluated; the experimental tests were carried out by using a power calibrator.     

Transport layer enhancements on a satellite‐based mobile broadband system for high‐speed trains

The great diffusion of wireless portable and handheld devices, along with the growing availability of applications on the Internet, led to a significant increase in the demand of access. Users require to continue business or private activities when moving, with performance at least comparable with that experienced over fixed networks. A very interesting scenario encompasses broadband and uninterrupted access over high‐speed trains. Developments of new telecommunication standards as well as innovative network architectures give the potential to fully match the aforementioned requirements. Nevertheless, there is a significant number of issues, especially related to system integration, mobility management, and propagation channel conditions, that need a careful analysis with the aim to support the design of real systems. This paper deals with this challenging scenario proposing a satellite‐based architecture in which DVB‐S2 and DVB‐RCS standards, MIPv6 at layer 3 (for handover management), and an enhanced TCP version at layer 4, named TCP Noordwijk, allow to achieve good performance. An NS‐2 enhanced simulator has supported the whole analysis. Results show the effectiveness of the proposed scheme against different modulation and coding configurations and compared with a selected set of TCP‐enhanced versions. Copyright © 2012 John Wiley & Sons, Ltd.     

Prevalence of Listeria monocytogenes in fresh and fermented Italian sausages and ribotyping of contaminating strains

Listeria monocytogenes has been detected in fresh as well as dry and semidry fermented sausages, rendering preparation and consumption of these products as a potential risk to human health. The aims of this study were (1) to evaluate the L. monocytogenes prevalence in 288 fresh and 237 fermented sausages produced in northern Italy; (2) to quantify the average pathogen Most Probable Number (MPN) per g of sausage; (3) to evaluate the sausage strain genetic diversity by automated PvuII ribotyping; and (4) to predict the pathogenicity lineage of these isolates determining their DuPont Identification Library Codes (DUP-IDs) by EcoRI ribotyping. The overall prevalence of L. monocytogenes in the sampled sausages was 28.2%. The percentage of L. monocytogenes positive fresh sausages was significantly higher than that of fermented sausages (i.e. 38.9 vs 15.2%), which had a pathogen load always lower than 10 MPN/g. In contrast, 16.1% of fresh sausages were contaminated by 10 to 100 MPN/g and 20.5% had more than 100 MPN/g. PvuII successfully discriminated sausage isolates with a Simpson's numerical index of discrimination of 0.637. A total of 12 and 9 different PvuII ribogroups were identified among 47 fresh and 24 fermented randomly selected sausage strains, respectively. Six of those ribogroups were shared between strains contaminating both kinds of sausages. According to the evaluation of the strain DUP-IDs, the majority of the isolates investigated in this study were part of the type II L. monocytogenes pathogenicity lineage, but type I lineage strains were identified among fermented sausage isolates. In conclusion, L. monocytogenes prevalence in Italian sausages was estimated to be around 28.2%. However, 84.2% of the samples were contaminated by less than 100 MPN of L. monocytogenes per g and the majority of L. monocytogenes contaminating strains would be classified in the type II pathogenicity lineage, including serotypes 1/2a, 1/2c and 3a.