Image Slicer Performances from a Demonstrator for the SNAP/JDEM Mission - Part I: Wavelength Accuracy

A well-adapted visible and infrared spectrograph has been developed for the SNAP (SuperNova/Acceleration Probe) experiment proposed for JDEM. The instrument should have a high sensitivity to see faint supernovae but also a good redshift determination better than 0.003(1+z) and a precise spectrophotometry (2%). An instrument based on an integral field method with the powerful concept of imager slicing has been designed. A large prototyping effort has been performed in France which validates the concept. In particular a demonstrator reproducing the full optical configuration has been built and tested to prove the optical performances both in the visible and in the near infrared range. This paper is the first of two papers. The present paper focus on the wavelength measurement while the second one will present the spectrophotometric performances. We adress here the spectral accuracy expected both in the visible and in the near infrared range in such configuration and we demonstrate, in particular, that the image slicer enhances the instrumental performances in the spectral measurement precision by removing the slit effect. This work is supported in France by CNRS/INSU/IN2P3 and by the French spatial agency (CNES) and in US by the University of California.Comment: Submitted to PAS

Integrating a Global Induction Mechanism into a Sequent Calculus

Most interesting proofs in mathematics contain an inductive argument which requires an extension of the LK-calculus to formalize. The most commonly used calculi for induction contain a separate rule or axiom which reduces the valid proof theoretic properties of the calculus. To the best of our knowledge, there are no such calculi which allow cut-elimination to a normal form with the subformula property, i.e. every formula occurring in the proof is a subformula of the end sequent. Proof schemata are a variant of LK-proofs able to simulate induction by linking proofs together. There exists a schematic normal form which has comparable proof theoretic behaviour to normal forms with the subformula property. However, a calculus for the construction of proof schemata does not exist. In this paper, we introduce a calculus for proof schemata and prove soundness and completeness with respect to a fragment of the inductive arguments formalizable in Peano arithmetic.Comment: 16 page

Spin-to-Orbital Angular Momentum Conversion in Semiconductor Microcavities

We experimentally demonstrate a technique for the generation of optical beams carrying orbital angular momentum using a planar semiconductor microcavity. Despite being isotropic systems, the transverse electric - transverse magnetic (TE-TM) polarization splitting featured by semiconductor microcavities allows for the conversion of the circular polarization of an incoming laser beam into the orbital angular momentum of the transmitted light field. The process implies the formation of topological entities, a pair of optical half-vortices, in the intracavity field

Sub MeV Particles Detection and Identification in the MUNU detector ((1)ISN, IN2P3/CNRS-UJF, Grenoble, France, (2)Institut de Physique, Neuch\^atel, Switzerland, (3) INFN, Padova Italy, (4) Physik-Institut, Z\"{u}rich, Switzerland)

We report on the performance of a 1 m$^{3}$ TPC filled with CF$_{4}$ at 3 bar, immersed in liquid scintillator and viewed by photomultipliers. Particle detection, event identification and localization achieved by measuring both the current signal and the scintillation light are presented. Particular features of $\alpha$ particle detection are also discussed. Finally, the ${54}$Mn photopeak, reconstructed from the Compton scattering and recoil angle is shown.Comment: Latex, 19 pages, 20 figure

The biological effects of bilirubin photoisomers

Although phototherapy was introduced as early as 1950's, the potential biological effects of bilirubin photoisomers (PI) generated during phototherapy remain unclear. The aim of our study was to isolate bilirubin PI in their pure forms and to assess their biological effects in vitro. The three major bilirubin PI (ZE- and EZ-bilirubin and Z-lumirubin) were prepared by photo-irradiation of unconjugated bilirubin. The individual photoproducts were chromatographically separated (TLC, HPLC), and their identities verified by mass spectrometry. The role of Z-lumirubin (the principle bilirubin PI) on the dissociation of bilirubin from albumin was tested by several methods: peroxidase, fluorescence quenching, and circular dichroism. The biological effects of major bilirubin PI (cell viability, expression of selected genes, cell cycle progression) were tested on the SH-SY5Y human neuroblastoma cell line. Lumirubin was found to have a binding site on human serum albumin, in the subdomain IB (or at a close distance to it); and thus, different from that of bilirubin. Its binding constant to albumin was much lower when compared with bilirubin, and lumirubin did not affect the level of unbound bilirubin (Bf). Compared to unconjugated bilirubin, bilirubin PI did not have any effect on either SH-SY5Y cell viability, the expression of genes involved in bilirubin metabolism or cell cycle progression, nor in modulation of the cell cycle phase. The principle bilirubin PI do not interfere with bilirubin albumin binding, and do not exert any toxic effect on human neuroblastoma cells

Applications of nuclear magnetic resonance spectroscopy: from drug discovery to protein structure and dynamics.

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors currently in clinical trials. This work combines screening of an FDA-approved drug panel and the identification of binders by protein-observed NMR. FDA-approved drugs salirasib and candesartan were identified as potent inhibitors in in vitro inhibition and migration assays while a weak inhibitor, olsalazine, was identified by NMR as the first small molecule inhibitor to directly bind PRL3. NMR was also used to validate the binding of additional compounds identified as experimental PRL3 inhibitors. Thienopyridone, a potent experimental inhibitor, did not show direct binding to PRL3 but instead inhibited phosphatase activity via redox mechanism. NMR also revealed that other experimental inhibitors did not engage PRL3. Thus, there remains a need to identify potent PRL3-directed inhibitors. Meanwhile, molecular modeling revealed a putative druggable site that has not been thoroughly explored before. The current study provides some scaffolds such as candesartan and particularly, olsalazine, the only binder identified, that could be the starting point of further drug discovery efforts, as well as a putative site that can be targeted in silico. MDMX, a negative regulator of p53, is another important therapeutic target in cancer, along with the homologous protein, MDM2. Inhibitors that block the MDM2-p53 interaction have been identified and despite similarities in the binding site of these homologous proteins, these inhibitors are ineffective against MDMX. It is hypothesized that the flexibility of MDMX contributes to this significant difference in response to inhibitors, despite comparable affinity to their endogenous target, p53. Examination of available inhibitor-bound structures of MDMX reveal a conserved pharmacophore but the structures adopt distinct conformations away from the binding site. This implies that global motions of the protein might contribute to molecular recognition. The conformational heterogeneity in MDMX was further confirmed by collecting residual dipolar couplings (RDCs). Further investigations on both MDMX and MDM2 are necessary to uncover whether the flexibility of MDMX contributes to the differential binding to inhibitors. Finally, NMR relaxation methods and state-of-the-art high-power Carr-Purcell-Meiboom Gill (CPMG) relaxation dispersion measurements, the first documented application on an enzyme, were used to characterize the solution dynamics of GMPK and the changes in dynamics upon GMP binding. Substrate binding resulted in restricting the amplitudes of motion for backbone amide bonds within the picosecond-nanosecond timescale. Meanwhile, CPMG showed dispersion in both in the absence and presence of GMP, such that substrate binding did not quench dynamics within the microsecond-millisecond timescale. Interestingly, more residues are observed to have dispersion in the bound form, some near the C-terminal of helix 3, which has previously been proposed to be involved in product release. Current studies show that substrate binding affect different timescales of protein motion. Future work shall follow how motions within different timescales are affected as GMPK processes its substrates – such as, for instance, binding of ATP analogs within the ATP binding site or simultaneous occupancy of both substrate binding pockets. This paves the way for a complete picture of the relationship of function and dynamics in the conformational enzymatic cycle of a bi-substrate enzyme using GMPK as a model. The current work illustrates some of the diverse applications of NMR on three unique systems that are also drug targets. Information collected here can be leveraged on future structure and dynamics studies as well as drug discovery efforts targeting any of these proteins

Generalisation through negation and predicate invention

The ability to generalise from a small number of examples is a fundamental challenge in machine learning. To tackle this challenge, we introduce an inductive logic programming (ILP) approach that combines negation and predicate invention. Combining these two features allows an ILP system to generalise better by learning rules with universally quantified body-only variables. We implement our idea in NOPI, which can learn normal logic programs with predicate invention, including Datalog programs with stratified negation. Our experimental results on multiple domains show that our approach can improve predictive accuracies and learning times

Standalone vertex finding in the ATLAS muon spectrometer

A dedicated reconstruction algorithm to find decay vertices in the ATLAS muon spectrometer is presented. The algorithm searches the region just upstream of or inside the muon spectrometer volume for multi-particle vertices that originate from the decay of particles with long decay paths. The performance of the algorithm is evaluated using both a sample of simulated Higgs boson events, in which the Higgs boson decays to long-lived neutral particles that in turn decay to bbar b final states, and pp collision data at √s = 7 TeV collected with the ATLAS detector at the LHC during 2011

Symmetry-breaking Effects for Polariton Condensates in Double-Well Potentials

We study the existence, stability, and dynamics of symmetric and anti-symmetric states of quasi-one-dimensional polariton condensates in double-well potentials, in the presence of nonresonant pumping and nonlinear damping. Some prototypical features of the system, such as the bifurcation of asymmetric solutions, are similar to the Hamiltonian analog of the double-well system considered in the realm of atomic condensates. Nevertheless, there are also some nontrivial differences including, e.g., the unstable nature of both the parent and the daughter branch emerging in the relevant pitchfork bifurcation for slightly larger values of atom numbers. Another interesting feature that does not appear in the atomic condensate case is that the bifurcation for attractive interactions is slightly sub-critical instead of supercritical. These conclusions of the bifurcation analysis are corroborated by direct numerical simulations examining the dynamics of the system in the unstable regime.MICINN (Spain) project FIS2008- 0484