Influence of incoherent scattering on stochastic deflection of high-energy negative particle beams in bent crystals

An investigation on stochastic deflection of high-energy negatively charged particles in a bent crystal was carried out. On the basis of analytical calculation and numerical simulation it was shown that it exists a maximum angle at which most of the beam is deflected. The existence of a maximum, which is taken in the correspondence of the optimal radius of curvature, is a novelty with respect to the case of positively charged particles, for which the deflection angle can be freely increased by increasing the crystal length. This difference has to be ascribed to the stronger contribution of incoherent scattering affecting the dynamics of negative particles that move closer to atomic nuclei and electrons. We therefore identified the ideal parameters for the exploitation of axial confinement for negatively charged particle beam manipulation in future high-energy accelerators, e.g., ILC or muon colliders

Planar channeling and quasichanneling oscillations in a bent crystal

Particles passing through a crystal under planar channeling experience transverse oscillations in their motion. As channeled particles approach the atomic planes of a crystal, they are likely to be dechanneled. This effect was used in ion-beam analysis with MeV energy. We studied this effect in a bent crystal for positive and negative particles within a wide range of energies in sight of application of such crystals at accelerators. We found the conditions for the appearance or not of channeling oscillations. Indeed a new kind of oscillations, strictly related to the motion of over-barrier particles, i.e. quasichanneling particles, has been predicted. Such oscillations, named planar quasichanneling oscillations, possess a different nature than channeling oscillations. Through computer simulation, we studied this effect and provided a theoretical interpretation for them. We show that channeling oscillations can be observed only for positive particles while quasichanneling oscillations can exist for particles with either sign. The conditions for experimental observation of channeling and quasichanneling oscillations at existing accelerators with available crystal has been found and optimized.Comment: 25 pages, 11 figure

IN SILICO APPROACHES IN DRUG DESIGN AND DEVELOPMENT: APPLICATIONS TO RATIONAL LIGAND DESIGN AND METABOLISM PREDICTION

In the last decades, the applications of computational methods in medicinal chemistry have experienced significant changes which have incredibly expanded their approaches, and more importantly their objectives. The overall aim of the present research project is to explore the different fields of the modelling studies by using well-known computational methods as well as different and innovative techniques. Indeed, computational methods traditionally consisted in ligand-based and the structure-based approaches substantially aimed at optimizing the ligand structure in terms of affinity, potency and selectivity. The studies concerning the muscarinic receptors in the present thesis applied these approaches for the rational design of novel improved bioactive molecules, interacting both in the orthosteric (e.g., 1,4-dioxane agonist) and in the allosteric sites. The research includes also the application of a novel method for target optimization, which consists in the generation of the so-called conformational chimeras to explore the flexibility of the modelled GPCR structures. In parallel, computational methods are finding successful applications in the research phase which precedes the ligand design and which is focused on a detailed validation and characterization of the biological target. A proper example of this kind of studies is given by the study regarding the purinergic receptors, which is aimed at the identification and characterization of potential allosteric binding pockets for the already reported inhibitors, exploiting also innovative approaches for binding site predictions (e.g., PELE, SPILLO-PBSS). Over time, computational applications felt a rich extension of their objectives and one of the clearest examples is represented by the ever increasing attempts to optimize the ADME/Tox profile of the novel compounds, so reducing the marked attrition in drug discovery caused by unsuitable pharmacokinetic profiles. Coherently, the first and main project of the present thesis regards the field of metabolism prediction and is founded on the meta-analysis and the corresponding database called MetaSar, manually collected from the recent specialized literature. This ongoing extended project includes different studies which are overall aimed at developing a comprehensive method for metabolism prediction. In detail, this Thesis reports an interesting application of the database which exploits an innovative predictive technique, the Proteochemometric modelling (PCM). This approach is indeed at the forefront of the latest modelling techniques, as it perfectly fits the growing request of new solutions to deal with the incredibly huge amount of data recently produced by the \u201comics\u201d disciplines. In this context, MetaSar represents an alternative and still appropriate source of data for PCM studies, which also enables the extension of its fields of application to a new avenue, such as the prediction of metabolism biotransformation. In the present thesis, we present the first example of these applications, which involves the building of a classification model for the prediction of the glucuronidation reaction. The field of glucuronidation reactions is exhaustively explored also through an homology modelling study aimed at defining the complete three-dimensional structure of the enzyme UGT2B7, the main isoform of glucuronidation enzymes in humans, in complex with the cofactor UDPGA and a typical substrate, such as Naproxen. The paths of the substrate entering to the binding site and the egress of the product have been investigated by performing Steered Molecular Dynamics (SMD) simulations, which were also useful to gain deeper insights regarding the full mechanism of action and the movements of the cofactor

How to make coherent bremsstrahlung circularly polarized

It is shown that if high energy positrons are moving in planar channeling conditions in a bent crystal at a small angle with respect to atomic strings which form the bent channeling planes, the hard part of the spectrum of gamma radiation emitted by the positrons will be highly circularly polarized. This Circularly Polarized String-of-Strings Radiation of Positrons Channeled in Bent Crystal (CPSOSRPCHBC) can be considered as a circularly polarized coherent bremsstrahlung manifesting itself efficiently from sub-GeV up to TeV and higher positron energies. The possibility to observe the CPSOSRPCHBC at the 500MeV positron beam of Frascati National Laboratory is considered

New approaches to the crystal collimation

Possibilities of application of the effects of multiple volume reflection in one crystal and of the channeling efficiency increase by the crystal cut or buried oxide layer are applied for the first time to the problem of crystal collimation. It is demonstrated that both these effects decrease the nuclear reaction rate in the crystal scraper and increase the average impact parameter of collisions of deflected protons with an absorber. However the crystal cut is efficient at precise crystal orientation corresponding to the channeling conditions while the MVROC effect can be applied at relatively rough crystal alignment

Electromagnetic radiation accompanying multiple volume reflection in one crystal

An interpretation of the first experiment on gamma-radiation of 120 GeV positrons experiencing multiple volume reflection from planes of one bent crystal is given. An increase of radiation of 10–20 GeV gamma quanta by multiple reflection from skewed planes is demonstrated. Also a considerable influence of the axial field on both hard and soft parts of the positron radiation spectrum is revealed

Data from docking simulations to develop an efficient strategy able to evaluate the interactions between RAGE and MDA-induced albumin adducts

This data article contains the results of docking simulations performed in order to develop a suitable in silico strategy able to assess the stability of the putative complexes between RAGE and MDA induced adducts on human albumin as experimentally determined doi: 10.1016/j.redox.2016.12.017, (Degani et al., 2017) [1]. The docking simulations involved different approaches to give a simplified yet realistic representation of the protein adducts and their environment. With increasing complexity, simulations involved the corresponding albumin tripeptides and pentapeptides with the modified residue in the central position as well as pseudo-structures which were generated by collecting the albumin residues around the adducted residue within a sphere of 7.5 \uc5 and 5 \uc5 radius. The reliability of the tested approaches was assessed by monitoring the score differences between adducted and unmodified residues. The obtained results revealed the greater predictive power of the spherical pseudo-structures compared to the simple tri- or pentapeptidic sequences thus suggesting that RAGE recognition involves residues which are spatially close to the modified residue even though not necessarily adjacent in the primary sequence

Electromagnetic dipole moments of charged baryons with bent crystals at the LHC

We propose a unique program of measurements of electric and magnetic dipole moments of charm, beauty and strange charged baryons at the LHC, based on the phenomenon of spin precession of channeled particles in bent crystals. Studies of crystal channeling and spin precession of positively- and negatively-charged particles are presented, along with feasibility studies and expected sensitivities for the proposed experiment using a layout based on the LHCb detector.Comment: 19 pages, 13 figure

Experimental evidence of planar channeling in a periodically bent crystal

The usage of a Crystalline Undulator (CU) has been identified as a promising solution for generating powerful and monochromatic $\gamma$-rays. A CU was fabricated at SSL through the grooving method, i.e., by the manufacturing of a series of periodical grooves on the major surfaces of a crystal. The CU was extensively characterized both morphologically via optical interferometry at SSL and structurally via X-ray diffraction at ESRF. Then, it was finally tested for channeling with a 400 GeV/c proton beam at CERN. The experimental results were compared to Monte Carlo simulations. Evidence of planar channeling in the CU was firmly observed. Finally, the emission spectrum of the positron beam interacting with the CU was simulated for possible usage in currently existing facilities