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Comment: 22 pages, Lectures given at the 2009 European School of High-Energy Physics, Bautzen, Germany, 14-27 Jun 2009
Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFP[Delta]6PLY) indicated that while the toxic activity of ...
Streptoccocus pneumoniae infection can result in local and systemic diseases such as otitis media, pneumonia and meningitis. Sensorineural hearing loss associated with this infection is mediated by the release of an exotoxin, pneumolysin. The goal of the present study was to characterize the mechanisms of pneumolysin toxicity in cochlear hair cells in vitro. Pneumolysin induced severe damage in cochlear hair cells, ranging from stereocilia disorganization to total cell loss. Surprisingly, pneumolysin-induced cell death preferentially targeted inner hair cells. Pneumolysin triggered in vitro cell death by an influx of calcium. Extracellular calcium appeared to enter the cell through a pore formed by the toxin. Buffering intracellular calcium with BAPTA improved hair cell survival. The mitochondrial apoptotic pathway involved in p...
This paper presents a novel approach to estimate the Standard Model backgrounds based on modifying Monte Carlo predictions within their systematic uncertainties. The improved background model is obtained by altering the original predictions with successively more complex correction functions in signal-free control selections. Statistical tests indicate when sufficient compatibility with data is reached. In this way, systematic effects are absorbed into the new background model. The same correction is then applied on the Monte Carlo prediction in the signal region. Comparing this method to other background estimation techniques shows improvements with respect to statistical and systematical uncertainties. The proposed method can also be applied in other fields beyond high energy physics.
We show results for the B meson decay constant calculated both for B mesons at rest and those with non-zero momentum and using both the temporal and spatial components of the axial vector current. It is an important check of lattice systematic errors that all these determinations of f(B) should agree. We also describe how well different smearings for the B meson work at non-zero momentum - the optimal smearing has a narrow smearing on the b quark.
Restriction-modification systems can protect bacteria against viral infection. Sequences of the hsdM gene, encoding one of the three subunits of type I restriction-modification systems, have been determined for four strains of enterobacteria. Comparison with the known sequences of EcoK and EcoR124 indicates that all are homologous, though they fall into three families (exemplified by EcoK, EcoA, and EcoR124), the first two of which are apparently allelic. The extent of amino acid sequence identity between EcoK and EcoA is so low that the genes encoding them might be better termed pseudoalleles; this almost certainly reflects genetic exchange among highly divergent species. Within the EcoK family the ratio of intra- to interspecific divergence is very high. The extent of divergence between the genes from Escherichia coli K-12 and Salmon...
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