Supramolecular modification of ABC triblock terpolymers in confinement assembly

The self-assembly of AB diblock copolymers in three-dimensional (3D) soft confinement of nanoemulsions has recently become an attractive bottom up route to prepare colloids with controlled inner morphologies. In that regard, ABC triblock terpolymers show a more complex morphological behavior and could thus give access to extensive libraries of multicompartment microparticles. However, knowledge about their self-assembly in confinement is very limited thus far. Here, we investigated the confinement assembly of polystyrene-block-poly(4-vinylpyridine)-block-poly(tert-butyl methacrylate) (PS-b-P4VP-b-PT or SVT) triblock terpolymers in nanoemulsion droplets. Depending on the block weight fractions, we found spherical microparticles with concentric lamella–sphere (ls) morphology, i.e., PS/PT lamella intercalated with P4VP spheres, or unusual conic microparticles with concentric lamella–cylinder (lc) morphology. We further described how these morphologies can be modified through supramolecular additives, such as hydrogen bond (HB) and halogen bond (XB) donors. We bound donors to the 4VP units and analyzed changes in the morphology depending on the binding strength and the length of the alkyl tail. The interaction with the weaker donors resulted in an increase in volume of the P4VP domains, which depends upon the molar fraction of the added donor. For donors with a high tendency of intermolecular packing, a visible change in the morphology was observed. This ultimately caused a shape change in the microparticle. Knowledge about how to control inner morphologies of multicompartment microparticles could lead to novel carbon supports for catalysis, nanoparticles with unprecedented topologies, and potentially, reversible shape changes by light actuation

Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysis

The antitumor agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (1) is a potent inhibitor of GSTP1-1, a glutathione S-transferase capable of inhibiting apoptosis by binding to JNK1 and TRAF2. We recently demonstrated that, unlike its parent compound, the benzoyl ester of 1 (compound 3) exhibits negligible reactivity towards GSH, and has a different mode of interaction with GSTP1-1. Unfortunately, 3 is susceptible to rapid metabolic hydrolysis. In an effort to improve the metabolic stability of 3, its ester group has been replaced by an amide, leading to N-(6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexyl)benzamide (4). Unlike 3, compound 4 was stable to human liver microsomal carboxylesterases, but retained the ability to disrupt the interaction between GSTP1-1 and TRAF2 regardless of GSH levels. Moreover, 4 exhibited both a higher stability in the presence of GSH and a greater cytotoxicity towards cultured A375 melanoma cells, in comparison with 1 and its analog 2. These findings suggest that 4 deserves further preclinical testing

Quantifying the unknown: issues in simulation validation and their experimental impact

The assessment of the reliability of Monte Carlo simulations is discussed, with emphasis on uncertainty quantification and the related impact on experimental results. Methods and techniques to account for epistemic uncertainties, i.e. for intrinsic knowledge gaps in physics modeling, are discussed with the support of applications to concrete experimental scenarios. Ongoing projects regarding the investigation of epistemic uncertainties in the Geant4 simulation toolkit are reported.Comment: To be published in the Proceedings of the 13th ICATPP Conference on Astroparticle, Particle, Space Physics and Detectors for Physics Applications, Villa Olmo, Como, 3-7 October 201

Research in Geant4 electromagnetic physics design, and its effects on computational performance and quality assurance

The Geant4 toolkit offers a rich variety of electromagnetic physics models; so far the evaluation of this Geant4 domain has been mostly focused on its physics functionality, while the features of its design and their impact on simulation accuracy, computational performance and facilities for verification and validation have not been the object of comparable attention yet, despite the critical role they play in many experimental applications. A new project is in progress to study the application of new design concepts and software techniques in Geant4 electromagnetic physics, and to evaluate how they can improve on the current simulation capabilities. The application of a policy-based class design is investigated as a means to achieve the objective of granular decomposition of processes; this design technique offers various advantages in terms of flexibility of configuration and computational performance. The current Geant4 physics models have been re-implemented according to the new design as a pilot project. The main features of the new design and first results of performance improvement and testing simplification are presented; they are relevant to many Geant4 applications, where computational speed and the containment of resources invested in simulation production and quality assurance play a critical role.Comment: 4 pages, 4 figures and images, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

New models for PIXE simulation with Geant4

Particle induced X-ray emission (PIXE) is a physical effect that is not yet adequately modelled in Geant4. The current status as in Geant4 9.2 release is reviewed and new developments are described. The capabilities of the software prototype are illustrated in application to the shielding of the X-ray detectors of the eROSITA telescope on the upcoming Spectrum-X-Gamma space mission.Comment: To be published in the Proceedings of the CHEP (Computing in High Energy Physics) 2009 conferenc

Diltiazem downregulates IL-12 production by human dendritic cells

It is well known that IL-12 plays a central role in the initiation and control of allogeneic immune response. It promotes the proliferation of lymphocytes and NK cells, cytotoxic activity of NK cells, and CTL. It was recently shown that IL-12 is involved in the regulation of T helper Th1-Th2 responses by exerting stimulatory effects on Th1 and inhibitory effects on Th2. This regulatory role is believed to result from the ability of IL-12 to induce IFN-γ production in activated T cells and NK cells.[1 and 2] Th1 cytokines (IL-2 and IFN-γ) promote both CTL and delayed-type hypersensitivity (DTH) responses, which are considered the principal effector mechanisms of allograft rejection. Diltiazem, a calcium channel blocker used in organ transplantation, is often included in clinical protocols in association with cyclosporin A and corticosteroids.[3] It was used initially because of its antinephrotoxic and antihypertensive effects, so that the undesirable side effects induced by immunosuppressive therapy could be reduced. We previously studied the effect of diltiazem on human mixed lymphocyte reactions (MLR) and on isolated human monocytes, showing the capacity of this drug to affect proinflammatory cytokine production.[4 and 5] Since dendritic cells (DCs) are the most effective antigen-presenting cells (APCs) to prime naive T cells, we were interested in determining the influence of diltiazem on human DCs. Human DCs generated from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) have been characterised as immature DCs. To become fully potent APCs, DCs must undergo maturation induced either by a proinflammatory signal such as lipopolysaccharide (LPS) or by interaction with CD40L expressed on activated T lymphocytes. [6] The ability of mature DCs to act as potent APCs is due to their high expression of MHC and costimulatory molecules and also to their production of cytokines, especially IL-12. Therefore, we determined the effect of diltiazem on cytokine production by human DCs with a particular interest in IL-1β, IL-6, TNF-α, and IL-12 production

Geant4-related R&D for new particle transport methods

A R&D project has been launched in 2009 to address fundamental methods in radiation transport simulation and revisit Geant4 kernel design to cope with new experimental requirements. The project focuses on simulation at different scales in the same experimental environment: this set of problems requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. An exploration is also foreseen about exploiting and extending already existing Geant4 features to apply Monte Carlo and deterministic transport methods in the same simulation environment. An overview of this new R&D associated with Geant4 is presented, together with the first developments in progress.Comment: 4 pages, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland

Status of the Cylindical-GEM project for the KLOE-2 Inner Tracker

The status of the R&D on the Cylindrical-GEM (CGEM) detector foreseen as Inner Tracker for KLOE-2, the upgrade of the KLOE experiment at the DAFNE phi-factory, will be presented. The R&D includes several activities: i) the construction and complete characterization of the full-size CGEM prototype, equipped with 650 microns pitch 1-D longitudinal strips; ii) the study of the 2-D readout with XV patterned strips and operation in magnetic field (up to 1.5T), performed with small planar prototypes in a dedicated test at the H4-SPS beam facility; iii) the characterization of the single-mask GEM technology for the realization of large-area GEM foils.Comment: 4 pages, 10 figures, Presented at Vienna Conference on Instrumentation (Feb 15-20, 2010, Vienna, Austria). Submitted to the Proceeding

Inter-Comparison and Validation of Geant4 Photon Interaction Models

A R&D project, named Nano5, has been recently launched to study an architectural design in view of addressing new experimental issues related to particle transport in high energy physics and other related physics disciplines with Geant4. In this frame, the first step has involved the redesign of the photon interaction models currently available in Geant4; this task has motivated a thorough investigation of the physics and computational features of these models, whose first results are presented here.Comment: 4 pages, 7 figures and images, 2 tables, to appear in proceedings of the Nuclear Science Symposium and Medical Imaging Conference 2009, Orland