A grid environment for high-throughput proteomics

We connect in a grid-enabled pipeline an ontology-based environment for proteomics spectra management with a machine learning platform for unbiased predictive analysis. We exploit two existing software platforms (MS-Analyzer and BioDCV), the emerging proteomics standards, and the middleware and computing resources of the EGEE Biomed VO grid infrastructure. In the setup, BioDCV is accessed by the MS-Analyzer workflow as a Web service, thus providing a complete grid environment for proteomics data analysis. Predictive classification studies on MALDI-TOF data based on this environment are presented.     

Phenotypic Characterization of Immortalized Chondrocytes from a Desbuquois Dysplasia Type 1 Mouse Model: A Tool for Studying Defects in Glycosaminoglycan Biosynthesis

The complexity of skeletal pathologies makes use of in vivo models essential to elucidate the pathogenesis of the diseases; nevertheless, chondrocyte and osteoblast cell lines provide relevant information on the underlying disease mechanisms. Due to the limitations of primary chondrocytes, immortalized cells represent a unique tool to overcome this problem since they grow very easily for several passages. However, in the immortalization procedure the cells might lose the original phenotype; thus, these cell lines should be deeply characterized before their use. We immortalized primary chondrocytes from a Cant1 knock-out mouse, an animal model of Desbuquois dysplasia type 1, with a plasmid expressing the SV40 large and small T antigen. This cell line, based on morphological and biochemical parameters, showed preservation of the chondrocyte phenotype. In addition reduced proteoglycan synthesis and oversulfation of glycosaminoglycan chains were demonstrated, as already observed in primary chondrocytes from the Cant1 knock-out mouse. In conclusion, immortalized Cant1 knock-out chondrocytes maintained the disease phenotype observed in primary cells validating the in vitro model and providing an additional tool to further study the proteoglycan biosynthesis defect. The same approach might be extended to other cartilage disorders.     

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.     

先进的感应热处理技术和设计方法

概述了用于热处理和表面处理的先进的感应技术以及现代设计方法,尤其是不同金属的感应化学热处理和同步双频淬火等最新技术。论文素材源自有关文献资料和作为Fluxtrol公司研究中心主任的作者的第一手经验。先进的设计方法采用了应用计算机模拟和计算机辅助技术,利用现代软件使感应系统的初步设计及其优化和性能预测成为可能。所制订的解决方案和用来确认被处理材料效果的试样的制备均需通过试验进行验证。感应工艺和工具(感应器、淬火环等)广泛采用模拟技术设计和制作,由于精度高,接近于实际的工艺和设备,可被称作"虚拟试制"。要特别关注感应系统中能改进系统参数、节能和提高热处理质量的磁通量控制。     

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.     

Human therapeutic plasma levels of the selective serotonin reuptake inhibitor (SSRI) sertraline decrease serotonin reuptake transporter binding and shelter-seeking behavior in adult male fathead minnows

Selective serotonin reuptake inhibitors (SSRIs) represent a class of pharmaceuticals previously reported in aquatic ecosystems. SSRIs are designed to treat depression and other disorders in humans, but are recognized to elicit a variety of effects on aquatic organisms, ranging from neuroendocrine disruption to behavioral perturbations. However, an understanding of the relationships among mechanistic responses associated with SSRI targets and ecologically important behavioral responses of fish remains elusive. Herein, linking Adverse Outcomes Pathways (AOP) models with internal dosimetry represent potential approaches for developing an understanding of pharmaceutical risks to aquatic life. We selected sertraline as a model SSRI for a 28-d study with adult male fathead minnows. Binding activity of the serotonin reuptake transporter (SERT), previously demonstrated in mammals and fish models to respond to sertraline exposure, was selected as an endpoint associated with therapeutic activity. Shelter-seeking behavior was monitored using digital tracking software to diagnose behavioral abnormalities. Fish plasma levels of sertraline exceeding human therapeutic doses were accurately modeled from external exposure concentrations when pH influences on ionization and log D were considered. We observed statistically significant decreases in binding at the therapeutic target (SERT) and shelter-seeking behavior when fish plasma levels exceeded human therapeutic thresholds. Such observations highlights the strengths of coupling physiologically based pharmacokinetic modeling and AOP approaches and suggest that internal dosimetry should be monitored to advance an understanding of the ecological consequences of SSRI exposure to aquatic vertebrates.     

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.