The balanced Voronoi formulas for GL(n)

In this paper we show how the GL(N) Voronoi summation formula of [MiSc2] can be rewritten to incorporate hyper-Kloosterman sums of various dimensions on both sides. This generalizes a formula for GL(4) with ordinary Kloosterman sums on both sides that was considered by Xiaoqing Li and the first-named author, and later by the second-named author in [Zho]

Coupled Oscillator Model for Nonlinear Gravitational Perturbations

Motivated by the gravity/fluid correspondence, we introduce a new method for characterizing nonlinear gravitational interactions. Namely we map the nonlinear perturbative form of the Einstein equation to the equations of motion of a collection of nonlinearly-coupled harmonic oscillators. These oscillators correspond to the quasinormal or normal modes of the background spacetime. We demonstrate the mechanics and the utility of this formalism within the context of perturbed asymptotically anti-de Sitter black brane spacetimes. We confirm in this case that the boundary fluid dynamics are equivalent to those of the hydrodynamic quasinormal modes of the bulk spacetime. We expect this formalism to remain valid in more general spacetimes, including those without a fluid dual. In other words, although borne out of the gravity/fluid correspondence, the formalism is fully independent and it has a much wider range of applicability. In particular, as this formalism inspires an especially transparent physical intuition, we expect its introduction to simplify the often highly technical analytical exploration of nonlinear gravitational dynamics.Comment: 17 pages, 3 figures. Minor fix to match published versio

A no-ghost theorem for the bosonic Nappi-Witten string

We prove a no-ghost theorem for a bosonic string propagating in Nappi-Witten spacetime. This is achieved in two steps. We first demonstrate unitarity for a class of NW/U(1) modules: the norm of any state which is primary with respect to a chosen timelike U(1) is non-negative. We then show that physical states - states satisfying the Virasoro constraints - in a class of modules of an affinisation of the Nappi-Witten algebra are contained in the NW/U(1) modules. Similar to the case of strings on $AdS_3$, in order to saturate the spectrum obtained in light-cone quantization we are led to include modules with energy not bounded from below, which are related to modules with energy bounded from below by spectral flow automorphisms.Comment: 24 pages, 1 figur

Structural and Functional Analysis of BipA, a Regulator of Virulence in Enteropathogenic Escherichia coli.

The translational GTPase BipA regulates the expression of virulence and pathogenicity factors in several eubacteria. BipA-dependent expression of virulence factors occurs under starvation conditions, such as encountered during infection of a host. Under these conditions, BipA associates with the small ribosomal subunit. BipA also has a second function to promote the efficiency of late steps in biogenesis of large ribosomal subunits at low temperatures, presumably while bound to the ribosome. During starvation, the cellular concentration of stress alarmone guanosine-3', 5'-bis pyrophosphate (ppGpp) is increased. This increase allows ppGpp to bind to BipA and switch its binding specificity from ribosomes to small ribosomal subunits. A conformational change of BipA upon ppGpp binding could explain the ppGpp regulation of the binding specificity of BipA. Here, we present the structures of the full-length BipA from Escherichia coli in apo, GDP-, and ppGpp-bound forms. The crystal structure and small-angle x-ray scattering data of the protein with bound nucleotides, together with a thermodynamic analysis of the binding of GDP and of ppGpp to BipA, indicate that the ppGpp-bound form of BipA adopts the structure of the GDP form. This suggests furthermore, that the switch in binding preference only occurs when both ppGpp and the small ribosomal subunit are present. This molecular mechanism would allow BipA to interact with both the ribosome and the small ribosomal subunit during stress response

Ethanol inhibits LPS-induced signaling and modulates cytokine production in peritoneal macrophages in vivo in a model for binge drinking

<p>Abstract</p> <p>Background</p> <p>Previous reports indicate that ethanol, in a binge drinking model in mice, inhibits the production of pro-inflammatory cytokines in vivo. However, the inhibition of signaling through TLR4 has not been investigated in this experimental model in vivo. Considering evidence that signaling can be very different in vitro and in vivo, the present study was conducted to determine if effects of ethanol on TLR4 signaling reported for cells in culture or cells removed from ethanol treated mice and stimulated in culture also occur when ethanol treatment and TLR4 activation occur in vivo.</p> <p>Results</p> <p>Phosphorylated p38, ERK, and c-Jun (nuclear) were quantified with kits or by western blot using samples taken 15, 30, and 60 min after stimulation of peritoneal macrophages with lipopolysaccharide in vivo. Effects of ethanol were assessed by administering ethanol by gavage at 6 g/kg 30 min before administration of lipopolysaccharide (LPS). Cytokine concentrations in the samples of peritoneal lavage fluid and in serum were determined at 1, 2, and 6 hr after lipopolysaccharide administration. All of these data were used to measure the area under the concentration vs time curve, which provided an indication of the overall effects of ethanol in this system. Ethanol suppressed production of most pro-inflammatory cytokines to a similar degree as it inhibited key TLR4 signaling events. However, NF-κB (p65) translocation to the nucleus was not inhibited by ethanol. To determine if NF-κB composed of other subunits was inhibited, transgenic mice with a luciferase reporter were used. This revealed a reproducible inhibition of NF-κB activity, which is consistent with the observed inhibition of cytokines whose expression is known to be NF-κB dependent.</p> <p>Conclusion</p> <p>Overall, the effects of ethanol on signalling in vivo were similar to those reported for in vitro exposure to ethanol and/or lipopolysaccharide. However, inhibition of the activation of NF-κB was not detected as translocation of p65 to the nucleus but was detected using transgenic reporter mice. The observation that ethanol given 24 hr before dosing with LPS modulated production of some cytokines indicates a persistent effect which does not require continued presence of ethanol.</p

Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H.

BackgroundOnly Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed.MethodsWe therefore evaluated our existing monoclonal antibodies (mAbs) to BoNT/A and BoNT/F for BoNT/H binding, created yeast-displayed mutants to select for higher-affinity-binding mAbs by using flow cytometry, and evaluated the mAbs' ability to neutralize BoNT/H in the standard mouse bioassay.ResultsAnti-BoNT/A HCC-binding mAbs RAZ1 and CR2 bound BoNT/H with high affinity. However, only 1 of 6 BoNT/F mAbs (4E17.2A) bound BoNT/H but with an affinity &gt;800-fold lower (equilibrium dissociation binding constant [KD] = 7.56 × 10(-8)M) than its BoNT/F affinity (KD= 9.1 × 10(-11)M), indicating that the N-terminal two-thirds of BoNT/H is immunologically unique. The affinity of 4E17.2A for BoNT/H was increased &gt;500-fold to KD= 1.48 × 10(-10)M (mAb 4E17.2D). A combination of mAbs RAZ1, CR2, and 4E17.2D completely protected mice challenged with 280 mouse median lethal doses of BoNT/H at a mAb dose as low as 5 µg of total antibody.ConclusionsThis 3-mAb combination potently neutralized BoNT/H and represents a potential human antitoxin that could be developed for the prevention and treatment of type H botulism