Transfected poly(I:C) activates different dsRNA receptors leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells

Background: Castration-resistant prostate cancer (CRPC) is refractory to chemo-radiotherapy. Results: Transfection of the synthetic analog of dsRNA poly(I:C) simultaneously stimulates apoptosis and IFN- expression through different pathways in androgen-independent prostate cancer (PCa) cells. Conclusion: Dual parallel pathways triggered by distinct receptors activate direct and immunologically mediated antitumor effects in advanced PCa. Significance: The proapoptotic/immunoadjuvant poly(I:C)-Lipofectamine complex may offer new therapeutic insights into CRPC

A multifunctional, synthetic Gaussia princeps luciferase reporter for live imaging of Candida albicans infections

Peer reviewedPublisher PD

Modeling Subgrid Viscosity for Advection--Diffusion Problems

We analyse the effect of the subgrid viscosity on a finite element discretisation, with piecewise linear elements, of a linear advection-diffusion scalar equation. We point out the importance of a proper tune-up of the viscosity coefficient, and we propose a heuristic method for obtaining reasonable values for it. The extension to more general problems is then hinted in the last section

Reconfigurable Computing and Hardware/Software Codesign

none3Article ID 731830 - EditorialPLAKS T. P; SANTAMBROGIO M. D; D. SCIUTOPLAKS T., P; Santambrogio, MARCO DOMENICO; Sciuto, Donatell

4-(3-Nitrophenyl)thiazol-2-ylhydrazone derivatives as antioxidants and selective hMAO-B inhibitors: synthesis, biological activity and computational analysis

A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesised, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure–activity relationships. The results of the biological testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a phenyl ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. In addition, the most potent and selective MAO-B inhibitors were evaluated in silico as potential cholinesterase (AChE/BuChE) inhibitors and in vitro for antioxidant activities. The results obtained from molecular modelling studies provided insight into the multiple interactions and structural requirements for the reported MAO inhibitory properties

Detection, characterization and sizing of hydrogen induced cracking in pressure vessels using phased array ultrasonic data processing

Pressure vessels operating in sour service conditions in refinery environments can be subject to the risk of H₂S cracking resulting from the hydrogen entering into the material. This risk, which is related to the specific working conditions and to the quality of the steel used, shall be properly managed in order to maintain the highest safety at a cost-effective level. Nowadays the typical management strategy is based on a risk based inspection (RBI) evaluation to define the inspection plan used in conjunction with a fitness for service (FFS) approach in defining if the vessel, although presenting dangerous defects such as cracks, can still be considered “fit for purpose” for a given time window based on specific fracture mechanics analysis. These vessels are periodically subject to non-destructive evaluation, typically ultrasonic testing. Phased Array (PA) ultrasonic is the latest technology more and more used for this type of application. This paper presents the design and development of an optimized Phased Array ultrasonic inspection technique for the detection and sizing of hydrogen induced cracking (HIC) type flaws used as reference for comparison. Materials used, containing natural operational defects, were inspected in “as-service” conditions. Samples have then been inspected by means of a “full matrix capture” (FMC) acquisition process followed by “total focusing method” (TFM) data post processing. FCM-TFM data have been further post-processed and then used to create a 3D geometrical reconstruction of the volume inspected. Results obtained show the significant improvement that FMC/TFM has over traditional PA inspection techniques both in terms of sensitivity and resolution for this specific type of defect. Moreover, since the FMC allows for the complete time domain signal to be captured from every element of a linear array probe, the full set of data is available for post-processing. Finally, the possibility to reconstruct the geometry of the component from the scans, including the defects present in its volume, represents the ideal solution for a reliable data transferring process to the engineering function for the subsequent FFS analysi

Benzo[b]tiophen-3-ol derivatives as effective inhibitors of human monoamine oxidase: design, synthesis, and biological activity

A series of benzo[b]thiophen-3-ols were synthesised and investigated as potential human monoamine oxidase (hMAO) inhibitors in vitro as well as ex vivo in rat cortex synaptosomes by means of evaluation of 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio and lactate dehydrogenase (LDH) activity. Most of these compounds possessed high selectivity for the MAO-B isoform and a discrete antioxidant and chelating potential. Molecular docking studies of all the compounds underscored potential binding site interactions suitable for MAO inhibition activity, and suggested structural requirements to further improve the activity of this scaffold by chemical modification of the aryl substituents. Starting from this heterocyclic nucleus, novel lead compounds for the treatment of neurodegenerative disease could be developed

Design and Characterization of Glyceryl Monooleate-Nanostructures Containing Doxorubicin Hydrochloride

Glyceryl monooleate (GMO) is one of the most popular amphiphilic lipids, which, in the presence of dierent amounts of water and a proper amount of stabilizer, can promote the development of well defined, thermodynamically stable nanostructures, called lyotropic liquid crystal dispersions. The aim of this study is based on the design, characterization, and evaluation of the cytotoxicity of lyotropic liquid crystal nanostructures containing a model anticancer drug such as doxorubicin hydrochloride. The drug is eciently retained by the GMO nanosystems by a remote loading approach. The nanostructures prepared with dierent non-ionic surfactants (poloxamers and polysorbates) are characterized by dierent physico-chemical features as a function of several parameters, i.e., serum stability, temperature, and dierent pH values, as well as the amount of cryoprotectants used to obtain suitable freeze-dried systems. The nanostructures prepared with poloxamer 407 used as a stabilizer show an increased toxicity of the entrapped drug on breast cancer cell lines (MCF-7 and MDA-MB-231) due to their ability to sensitize multidrug-resistant (MDR) tumor cells through the inhibition of specific drug eux transporters. Moreover, the interaction between the nanostructures and the cells occurs after just a few hours, evidencing a huge cellular uptake of the nanosystems