Use of functional imaging across clinical phases in CNS drug development

The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases across all clinical phases (I–IV) of drug development. The evolution of functional imaging and the promise it holds to contribute to drug development will require the development of standards (including good imaging practice), but, if well integrated into drug development, functional imaging can define markers of CNS penetration, drug dosing and target engagement (even for drugs that are not amenable to positron emission tomography imaging) in phase I; differentiate objective measures of efficacy and side effects and responders vs non-responders in phase II, evaluate differences between placebo and drug in phase III trials and provide insights into disease modification in phase IV trials

A hardware implementation of Region-of-Interest selection in LAr-TPC for data reduction and triggering

Large Liquid Argon TPC detectors in the range of multikton mass for neutrino and astroparticle physics require the extraction and treatment of signals from some 105 wires. In order to enlarge the throughtput of the DAQ system an on-line lossless data compression has been realized reducing almost a factor 4 the data flow. Moreover a trigger system based on a new efficient on-line identification algorithm of wire hits was studied, implemented on the actual ICARUS digital read- out boards and fully tested on the ICARINO LAr-TPC facility operated at LNL INFN Laboratory with cosmic-rays. Capability to trigger isolated low energy events down to 1 MeV visible energy was also demonstrated.Comment: 26 pages, 26 Figure; to be submitted to JINS

Operation of a LAr-TPC equipped with a multilayer LEM charge readout

A novel detector for the ionization signal in a single phase LAr-TPC, based on the adoption of a multilayer Large Electron Multiplier (LEM) replacing the traditional anodic wire arrays, has been experimented in the ICARINO test facility at the INFN Laboratories in Legnaro. Cosmic muon tracks were detected allowing the measurement of energy deposition and a first determination of the signal to noise ratio. The analysis of the recorded events demonstrated the 3D reconstruction capability of ionizing events in this device in liquid Argon, collecting a fraction of about 90% of the ionization signal with signal to noise ratio similar to that measured with more traditional wire chambersComment: 9 pages, 7 Figure

The Lie derivative of spinor fields: theory and applications

Starting from the general concept of a Lie derivative of an arbitrary differentiable map, we develop a systematic theory of Lie differentiation in the framework of reductive G-structures P on a principal bundle Q. It is shown that these structures admit a canonical decomposition of the pull-back vector bundle i_P^*(TQ) = P\times_Q TQ over P. For classical G-structures, i.e. reductive G-subbundles of the linear frame bundle, such a decomposition defines an infinitesimal canonical lift. This lift extends to a prolongation Gamma-structure on P. In this general geometric framework the concept of a Lie derivative of spinor fields is reviewed. On specializing to the case of the Kosmann lift, we recover Kosmann's original definition. We also show that in the case of a reductive G-structure one can introduce a "reductive Lie derivative" with respect to a certain class of generalized infinitesimal automorphisms, and, as an interesting by-product, prove a result due to Bourguignon and Gauduchon in a more general manner. Next, we give a new characterization as well as a generalization of the Killing equation, and propose a geometric reinterpretation of Penrose's Lie derivative of "spinor fields". Finally, we present an important application of the theory of the Lie derivative of spinor fields to the calculus of variations.Comment: 28 pages, 1 figur

Spin-polarized oxygen hole states in cation deficient La(1-x)CaxMnO(3+delta)

When holes are doped into a Mott-Hubbard type insulator, like lightly doped manganites of the La(1-x)CaxMnO3 family, the cooperative Jahn-Teller distortions and the appearance of orbital ordering require an arrangement of Mn(3+)/Mn(4+) for the establishment of the insulating canted antiferromagnetic (for x<=0.1), or of the insulating ferromagnetic (for 0.1<x<= 0.2) ground state. In the present work we provide NMR evidence about a novel and at the same time puzzling effect in La(1-x)CaxMnO(3+delta) systems with cation deficience. We show that in the low Ca-doping regime, these systems exhibit a very strong hyperfine field at certain La nuclear sites, which is not present in the stoichiometric compounds. Comparison of our NMR results with recent x-ray absorption data at the Mn K edge, suggests the formation of a spin-polarized hole arrangement on the 2p oxygen orbitals as the origin of this effect.Comment: 10 pages, 4 Figures, submitted to PR

Free electron lifetime achievements in Liquid Argon Imaging TPC

A key feature for the success of the liquid Argon imaging TPC (LAr-TPC) technology is the industrial purification against electro-negative impurities, especially Oxygen and Nitrogen remnants, which have to be continuously kept at an exceptionally low level by filtering and recirculating liquid Argon. Improved purification techniques have been applied to a 120 liters LAr-TPC test facility in the INFN-LNL laboratory. Through-going muon tracks have been used to determine the free electron lifetime in liquid Argon against electro-negative impurities. The short path length here observed (30 cm) is compensated by the high accuracy in the observation of the specific ionization of cosmic ray muons at sea level as a function of the drift distance. A free electron lifetime of (21.4+7.3-4.3) ms, namely > 15.8 ms at 90 % C.L. has been observed over several weeks under stable conditions, corresponding to a residual Oxygen equivalent of about 15 ppt (part per trillion). At 500 V/cm, the free electron speed is 1.5 m/ms. In a LAr-TPC a free electron lifetime in excess of 15 ms corresponds for instance to an attenuation of less than 15 % after a drift path of 5 m, opening the way to the operation of the LAr-TPC with exceptionally long drift distances.Comment: 15 pages, 10 figures; Accepted for publication in JINS

Molecular dynamics study of the fragmentation of silicon doped fullerenes

Tight binding molecular dynamics simulations, with a non orthogonal basis set, are performed to study the fragmentation of carbon fullerenes doped with up to six silicon atoms. Both substitutional and adsorbed cases are considered. The fragmentation process is simulated starting from the equilibrium configuration in each case and imposing a high initial temperature to the atoms. Kinetic energy quickly converts into potential energy, so that the system oscillates for some picoseconds and eventually breaks up. The most probable first event for substituted fullerenes is the ejection of a C2 molecule, another very frequent event being that one Si atom goes to an adsorbed position. Adsorbed Si clusters tend to desorb as a whole when they have four or more atoms, while the smaller ones tend to dissociate and sometimes interchange positions with the C atoms. These results are compared with experimental information from mass abundance spectroscopy and the products of photofragmentation.Comment: Seven two-column pages, six postscript figures. To be published in Physical Review