Patients who recover from pneumonia subsequently have elevated rates of death after hospital discharge as a result of secondary organ damage, the causes of which are unknown. We used the bacterium , a common cause of hospital-acquired pneumonia, as a model for investigating this phenomenon. We show that infection of pulmonary endothelial cells by induces production and release of a cytotoxic amyloid molecule with prion characteristics, including resistance to various nucleases and proteases. This cytotoxin was self-propagating, was neutralized by anti-amyloid Abs, and induced death of endothelial cells and neurons. Moreover, the cytotoxin induced edema in isolated lungs. Endothelial cells and isolated lungs were protected from cytotoxin-induced death by stimulation of signal transduction pathways that are linked to prion protein. Analysis of bronchoalveolar lavage fluid collected from human patients with pneumonia demonstrated cytotoxic activity, and lavage fluid contained amyloid molecules, including oligomeric τ and Aβ. Demonstration of long-lived cytotoxic agents after infection may establish a molecular link to the high rates of death as a result of end-organ damage in the months after recovery from pneumonia, and modulation of signal transduction pathways that have been linked to prion protein may provide a mechanism for intervention.-Balczon, R., Morrow, K. A., Zhou, C., Edmonds, B., Alexeyev, M., Pittet, J.-F., Wagener, B. M., Moser, S. A., Leavesley, S., Zha, X., Frank, D. W., Stevens, T. infection liberates transmissible, cytotoxic prion amyloids.

Determination of the ligand conformation on gold nanoparticle (AuNP) is of fundamental importance in nanoparticle research and applications. Using a combination of surface-enhanced Raman spectroscopy (SERS), density function calculation, and normal Raman spectroscopy, the pH dependence of mercaptobenzimadazole (MBI) adsorption onto AuNP was systematically studied. Structures and conformations of MBI adsorbates on AuNP were determined together with their binding constants, and saturation packing densities were determined at three different pHs (1.4, 7.9, and 12.5). While MBI thione is the predominant tautomer in solution with a pH value lower than 10.3, MBI thiolate is the main adsorbate on AuNP surface in solution with pH > 2. MBI thiones dominate the AuNP surface only in solutions with pH < 2. While MBI thione has a higher saturation packing density (∼632 pmol/cm 2 ) than MBI thiolate (∼540 pmol/cm 2 ), its binding constant (2.14 × 10 6 M -1 ) is about five times smaller than that for MBI thiolate (10.12 × 10 6 M -1 ). Using the MBI footprint deduced from its saturation packing density on AuNP, the conformation of MBI was determined. While the MBI thione binds monodentately to the AuNP with a perfectly upright orientation, MBI thiolate binds bidentately to AuNP with a tilt angle that allows interaction of AuNP with both the sulfur and the nitrogen atoms in MBI thiolate. In addition to the new insights provided on MBI binding onto gold nanoparticle, the methodology employed in this study can be particularly useful for studying AuNP interactions with other imidazole-thiol compounds, a class of heterocylic compounds that can exist in different tautomeric forms.

A synergistic approach combining the experimental photoelectron spectroscopy and theoretical electronic structure studies is used to probe the geometrical structure and the spin magnetic moment of Co(n)(pyridine)(m) (-) clusters. It is predicted that the ground state of Co(pyridine)(-) is a structure where the Co atom is inserted in a CH bond. However, the insertion is marked by a barrier of 0.33 eV that is not overcome under the existing experimental conditions resulting in the formation of a structure where Co occupies a site above the pyridine plane. For Co(2)(pyridine)(-), a ground-state structure is predicted in which the Co(2) diametric moiety is inserted in one of the CH bonds, but again because of a barrier, the structure which matches the photoelectron spectrum is a higher-energy isomer in which the Co(2) moiety is bonded directly to nitrogen on the pyridine ring. In all cases, the Co sites have finite magnetic moments suggesting that the complexes may provide ways of making cluster-based magnetic materials.

New boundary conditions are imposed on the familiar cylindrical gravitational wave vacuum spacetimes. The new spacetime family represents cylindrical waves in a flat expanding (Kasner) universe. Space sections are flat and nonconical where the waves have not reached and wave amplitudes fall off more rapidly than they do in Einstein-Rosen solutions, permitting a more regular null inifinity.This paper shows how to construct exact solutions for compact cylindrical gravitational wave pulses spreading in an expanding universe that is spatially flat at large cylindrical radius, where the waves have not reached. The universal expansion is restricted to the translation-direction (or z-axis) of cylindrical symmetry. The remaining directions show gravitational waves spreading in a three-dimensional spacetime that can be exactly Minkowskian before the wave pulse. The effective three dimensional spacetime has a completely regular conformal compactification so that a radiation zone at future null infinity is well defined without any rescaling of fields. This simple behavior makes these solutions ideal for testing the numerical simulation codes that are used to predict gravitational waves from compact sources. Because they have the simplicity of Einstein-Rosen solutions but are compatible with the boundary conditions of the real universe, these new solutions may model localized inhomogeneities in Big Bang cosmologies and may also provide an interesting restricted framework for testing formal ideas such as quantum gravity.The original Einstein-Rosen cylindrical wave solutions of Einstein's vacuum field equations[1, 2] inhabit a universe that is conical rather than flat at infinite cylindrical radius [3] and which, apart from the oscillations of the waves, does not evolve in time. Thus, they are not good models for inhomogeneities in our own universe, which is thought to be spatially flat and expanding and do not make convenient test cases for numerical simulations of gravitational waves from compact sources. However, the boundary conditions can be changed. Cylindrically symmetric (G 2 ) exact solutions with closed space sections of S 3 , S 1 × S 2 and S 1 × S 1 × S 1 (three-torus) topologies are known and have proven useful as toy models of inhomogeneous cosmologies.[4, 5, 6] The three-torus solutions, in particular, can be regarded as standing-gravitational-wave inhomogeneous generalizations of spatially flat Kasner universes [7,8,9,10] and have provided useful test cases for validating numerical simulations of Einstein's field equations. [11,12] Here, we will change the boundary conditions again.We will use the notation of earlier papers [4,5,6] on these spacetimes, but with some changes in coordinate names to fit the new circumstances. The isometry group coordinates are z and ϕ (instead of σ and δ used in the earlier papers), with z ranging from −∞ to +∞ and ϕ ranging from 0 to 2π. The remaining coordinates t, r each range from 0 to ∞. The isometry group consists of translations of z and of ϕ modulo 2π. Thus, each group orb...