Legionella pneumophila macrophage infectivity potentiator protein appendage domains modulate protein dynamics and inhibitor binding

Macrophage infectivity potentiator (MIP) proteins are widespread in human pathogens including Legionella pneumophila, the causative agent of Legionnaires' disease and protozoans such as Trypanosoma cruzi. All MIP proteins contain a FKBP (FK506 binding protein)-like prolyl-cis/trans-isomerase domain that hence presents an attractive drug target. Some MIPs such as the Legionella pneumophila protein (LpMIP) have additional appendage domains of mostly unknown function. In full-length, homodimeric LpMIP, the N-terminal dimerization domain is linked to the FKBP-like domain via a long, free-standing stalk helix. Combining X-ray crystallography, NMR and EPR spectroscopy and SAXS, we elucidated the importance of the stalk helix for protein dynamics and inhibitor binding to the FKBP-like domain and bidirectional crosstalk between the different protein regions. The first comparison of a microbial MIP and a human FKBP in complex with the same synthetic inhibitor was made possible by high-resolution structures of LpMIP with a [4.3.1]-aza-bicyclic sulfonamide and provides a basis for designing pathogen-selective inhibitors. Through stereospecific methylation, the affinity of inhibitors to L. pneumophila and T. cruzi MIP was greatly improved. The resulting X-ray inhibitor-complex structures of LpMIP and TcMIP at 1.49 and 1.34 Å, respectively, provide a starting point for developing potent inhibitors against MIPs from multiple pathogenic microorganisms.</p

Comparison of Geant4 hadron generation with data from the interactions with beryllium nuclei of +8.9 GeV/c protons and pions, and of -8 GeV/c pions

Hadron generation in the Geant4 simulation tool kit is compared with inclusive spectra of secondary protons and pions from the interactions with beryllium nuclei of +8.9 GeV/c protons and pions, and of -8.0 GeV/c pions. The data were taken in 2002 at the CERN Proton Synchrotron with the HARP spectrometer. We report on significant disagreements between data and simulated data especially in the polar-angle distributions of secondary protons and pions.Comment: 15 pages, 13 figure

A large displacement, high frequency, underwater microelectromechanical systems actuator

Here, we demonstrate an in situ electrostatic actuator that can operate underwater across a wide range of displacements and frequencies, achieving a displacement of approximately 10-μm at 500-Hz and 1-μm at 5-kHz; this performance surpasses that of existing underwater physical actuators. To attain these large displacements at such high speeds, we optimized critical design parameters using a computationally efficient description of the physics of low quality (Q) factor underwater electrostatic actuators. Our theoretical model accurately predicts actuator motion profiles as well as limits of bandwidth and displacement

Virtual Compton Scattering off a Spinless Target in AdS/QCD

We study the doubly virtual Compton scattering off a spinless target $\gamma^*P\to\gamma^*P'$ within the Anti-de Sitter(AdS)/QCD formalism. We find that the general structure allowed by the Lorentz invariance and gauge invariance of the Compton amplitude is not easily reproduced with the standard recipes of the AdS/QCD correspondence. In the soft-photon regime, where the semi-classical approximation is supposed to apply best, we show that the measurements of the electric and magnetic polarizabilities of a target like the charged pion in real Compton scattering, can already serve as stringent tests.Comment: 21 pages, version to be published in JHEP

One-step isolation and biochemical characterization of a highlyactive plant PSII monomeric core

We describe a one-step detergent solubilization protocol for isolating a highly active form of Photosystem II (PSII) from Pisum sativum L. Detailed characterization of the preparation showed that the complex was a monomer having no light harvesting proteins attached. This core reaction centre complex had, however, a range of low molecular mass intrinsic proteins as well as the chlorophyll binding proteins CP43 and CP47 and the reaction centre proteins D1 and D2. Of particular note was the presence of a stoichiometric level of PsbW, a low molecular weight protein not present in PSII of cyanobacteria. Despite the high oxygen evolution rate, the core complex did not retain the PsbQ extrinsic protein although there was close to a full complement of PsbO and PsbR and partial level of PsbP. However, reconstitution of PsbP and PsbPQ was possible. The presence of PsbP in absence of LHCII and other chlorophyll a/b binding proteins confirms that LHCII proteins are not a strict requirement for the assembly of this extrinsic polypeptide to the PSII core in contrast with the conclusion of Caffarri et al. (2009)

Interferometry of Direct Photons in Central 280Pb+208Pb Collisions at 158A GeV

Two-particle correlations of direct photons were measured in central 208Pb+208Pb collisions at 158 AGeV. The invariant interferometric radii were extracted for 100<K_T<300 MeV/c and compared to radii extracted from charged pion correlations. The yield of soft direct photons, K_T<300 MeV/c, was extracted from the correlation strength and compared to theoretical calculations.Comment: 5 pages, 4 figure