Measurement of residual nucleus cross sections and recoil energies in p + Fe collisions at 300, 500, 750, 1000 and 1500 MeV

The production of residual nuclei in p + Fe collisions has been measured at GSI on the FRS facility by means of the reverse kinematic techniques at 300, 500, 750, 1000 and 1500 MeV/A. The cross-sections larger than 0.01 mb of all isotopes with Z larger than 8 have been obtained. Velocity distributions were also measured. Comparisons to models describing spallation reactions and some empirical formulae often used in astrophysics are presented. These data are directly used to calculate impurety production and DPAs in a thin window as foreseen in spallation sources or accelerator-driven systems

Spallation Residues in the Reaction 56Fe + p at 0.3, 0.5, 0.75, 1.0 and 1.5 A GeV

The spallation residues produced in the bombardment of 56}Fe at 1.5, 1.0, 0.75, 0.5 and 0.3 A GeV on a liquid-hydrogen target have been measured using the reverse kinematics technique and the Fragment Separator at GSI (Darmstadt). This technique has permitted the full identification in charge and mass of all isotopes produced with cross-sections larger than 10^{-2} mb down to Z=8. Their individual production cross-sections and recoil velocities at the five energies are presented. Production cross-sections are compared to previously existing data and to empirical parametric formulas, often used in cosmic-ray astrophysics. The experimental data are also extensively compared to different combinations of intra-nuclear cascade and de-excitation models. It is shown that the yields of the lightest isotopes cannot be accounted for by standard evaporation models. The GEMINI model, which includes an asymmetric fission decay mode, gives an overall good agreement with the data. These experimental data can be directly used for the estimation of composition modifications and damages in materials containing iron in spallation sources. They are also useful for improving high precision cosmic-ray measurements.Comment: Submited to Phys. Rev. C (10/2006

Potent Inhibition of HIV-1 Replication by a Tat Mutant

Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection

Dynamic Measurements of Membrane Insertion Potential of Synthetic Cell Penetrating Peptides

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Langmuir, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/la403370p.Cell penetrating peptides (CPPs) have been established as excellent candidates for mediating drug delivery into cells. When designing synthetic CPPs for drug delivery applications, it is important to understand their ability to penetrate the cell membrane. In this paper, anionic or zwitterionic phospholipid monolayers at the air-water interface are used as model cell membranes to monitor the membrane insertion potential of synthetic CPPs. The insertion potential of CPPs having different cationic and hydrophobic amino acids were recorded using a Langmuir monolayer approach that records peptide adsorption to model membranes. Fluorescence microscopy was used to visualize alterations in phospholipid packing due to peptide insertion. All CPPs had the highest penetration potential in the presence of anionic phospholipids. In addition, two of three amphiphilic CPPs inserted into zwitterionic phospholipids, but none of the hydrophilic CPPs did. All the CPPs studied induced disruptions in phospholipid packing and domain morphology, which were most pronounced for amphiphilic CPPs. Overall, small changes to amino acids and peptide sequences resulted in dramatically different insertion potentials and membrane reorganization. Designers of synthetic CPPs for efficient intracellular drug delivery should consider small nuances in CPP electrostatic and hydrophobic properties

CNS Delivery Via Adsorptive Transcytosis

Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics

The SIde-Looking Coronagraph for the solar orbiter mission: Optical and mechanical designs

The SIde-Looking Coronagraph (SILC) is intented to be proposed as part of the payload of the Solar Orbiter mission of the European Space Agency. Solar Orbiter will follow elliptic orbits with a large range of heliocentric distance, from 0.21 to 0.6 AU, and will reach heliographic latitudes as high as 38°. Furthermore, the spacecraft will have an offset pointing capability so as to target any point of the solar disk. These characteristics, in addition to the severe thermal environment, are very restrictive for a coronagraph and lead us to propose an externally occulted coronagraph entirely protected from direct sunlight by remaining in the shadow of the spacecraft and looking sideways. The optical design follows the general principles of an externally occulted coronagraph adapted to the side-looking concept. Although SILC loses the full spatial coverage of the corona, it can observe the inner part of the corona (down to 1.5 solar radii) during the whole mission and compensate the off-pointing of the spacecraft. The optical and mechanical designs of SILC are presented in detail

ASPIICS, a giant externally occulted coronagraph for the PROBA-3 formation flying mission

International audienceFormation flying opens new perspectives for coronal physics, and allow to conceive giant, externally occulted coronagraphs using a two-component space system with the external occulter on one spacecraft and the optical instrument on the other spacecraft. ASPIICS (Association de Satellites Pour l'Imagerie et l'Interférométrie de la Couronne Solaire) is a mission proposed to ESA in the framework of the PROBA-3 program of formation flying which is presently in phase A, to exploit this technique for coronal observations. ASPIICS is composed of a single coronagraph which performs high spatial resolution imaging of the corona as well as 2-dimensional spectroscopy of several emission lines from the coronal base out to 3 R⊙. The selected lines allow to address different coronal regions: the forbidden line of Fe XIV at 530.285 nm (coronal matter), Fe IX/X at 637.4 nm (coronal holes), HeI at 587.6 nm (cold matter). An additional broad spectral channel will image the white light corona so as to derive electron densities. The classical design of an externally occulted coronagraph is adapted to the detection of the very inner corona as close as 1.01 R⊙ and the addition of a Fabry-Perot interferometer using a so-called " étalon". This paper is dedicated to the description of the optical design and its critical components: the entrance optics and the Fabry-Pérot interferometer. ASPIICS will address the question of coronal heating and of the role of waves by characterizing propagating fluctuations (waves and turbulence) in the solar wind acceleration region and by looking for oscillations in the intensity and Doppler shift of spectral lines. The combined imaging and spectral diagnostics capabilities available with ASPIICS will allow to map the velocity field of the corona both in the sky plane (directly on the images) and along the line-of-sight by measuring the Doppler shifts of emission lines. We will attempt to determine how the different components of the solar wind, slow and fast are accelerated. ASPIICS will observe the corona during the maximum of solar activity, insuring the detection of many Coronal Mass Ejections (CMEs). By rapidly alternating high resolution imaging and spectroscopy, CMEs will be thoroughly characterized. In addition, ASPIICS will attempt to characterize the topology of the magnetic field in the corona