The static potential between an infinitely heavy quark and antiquark is derived in the framework of perturbative QCD to three loops by performing a full calculation of the two-loop diagrams and using the renormalization group. The contribution of massless fermions is included.The force law between infinitely heavy quarks has been investigated since more than 20 years because of its importance for a deeper understanding of the strong interactions. The static quark-antiquark potential is a very fundamental concept, constituting the non-abelian analog to the Coulomb potential of electrodynamics, and also enters as a vital ingredient in the description of non-relativistic bound states like quarkonia. It is widely believed to consist of two parts: a Coulombic term at short distances which can be derived from field theory by using perturbative QCD, and a long-ranged confining term whose derivation from first principles presumably requires much more advanced methods. Although an analysis based on perturbation theory

We describe the physics potential of e + e − linear colliders in this report. These machines are planned to operate in the first phase at a center-of-mass energy of 500 GeV, before being scaled up to about 1 TeV. In the second phase of the operation, a final energy of about 2 TeV is expected. The machines will allow us to perform precision tests of the heavy particles in the Standard Model, the top quark and the electroweak bosons. They are ideal facilities for exploring the properties of Higgs particles, in particular in the intermediate mass range. New vector bosons and novel matter particles in extended gauge theories can be searched for and studied thoroughly. The machines provide unique opportunities for the discovery of particles in supersymmetric extensions of the Standard Model, the spectrum of Higgs particles, the supersymmetric partners of the electroweak gauge and Higgs bosons, and of the matter particles. High precision analyses of their properties and interactions will allow for extrapolations to energy scales close to the Planck scale where gravity becomes significant. In alternative scenarios, like compositeness models, novel matter particles and interactions can be discovered and investigated in the energy range above the existing colliders up to the TeV scale. Whatever scenario is realized in Nature, the discovery potential of e + e − linear colliders and the high-precision with which the properties of particles and their interactions can be analysed, define an exciting physics programme complementary to hadron machines.

Toll-like receptor 9 (TLR-9) recognizes unmethylated CpG dinucleotides which are abundant in prokaryotic DNA and yet are rare in eukaryotic DNA. Little is known about the significance of TLR-9 in terms of recognition of different bacterial DNA species. In this study HEK293 cells stably transfected with human TLR-9 were used to analyze the immunostimulatory properties of 15 bacterial DNA preparations. In addition, bacterial genome data were analyzed for the frequency of unmethylated cytosine-guanosine ([CG]) dinucleotides. We observed that DNA samples of different bacteria showed considerable differences in their potential to stimulate TLR-9. This correlated with the frequency of [CG] dinucleotides. Based upon data from our experiments the estimate of immunostimulatory bacterial DNA concentrations translated to as high as 10 9 bacteria/ml. Application of the transfection reagent DOTAP resulted in a more efficient delivery of DNA into the cell, and this went along with increased TLR-9 activation. The data indicate that bacterial DNA preparations from different species differ in their capacity to activate TLR-9, which is dependent on the individual [CG] content. Moreover, increased intracellular delivery results in a marked enhancement of immunostimulation.Innate immunity recognizes conserved microbial structures that are referred to as pathogen-associated molecular patterns (15). This is achieved by use of pattern recognition receptors, of which Toll-like receptors have been identified to play a crucial role. Prototypical substances constituting microbial patterns are components of the prokaryotic cell wall, e.g., lipopolysaccharide or lipoteichoic acid. However, it has been recognized early that also DNA possesses immunostimulatory potential when Tokunaga et al. identified DNA-containing fractions of mycobacteria to mediate immune modulation (23,25). Later it was shown that this is due to the relative abundance of unmethylated cytosine-guanosine ([CG]) dinucleotides (11). Indeed, vertebrate DNA shows a suppression of [CG] dinucleotide frequency and, moreover, is characterized by an increased rate of C-5 methylation of cytosine residues (24). TLR-9 has been identified as the DNA-recognizing receptor (7).It was noted early that stimulation by bacterial DNA could be mimicked by the use of [CG]-containing synthetic oligodesoxynucleotides (CpG-ODNs) (11). Since CpG-ODNs turned out to possess a considerable potential for immune modulation and since these compounds were easy to synthesize, subsequent work in the TLR-9 field has mainly focused on the use synthetic ODNs. It is intriguing that, despite the fact that basic principles in bacterial DNA/TLR-9 recognition have been known for years, information concerning the meaning of TLR-9 for infections or for the recognition of bacteria is still extremely limited.Differences in the C/G composition (implying differences in [CG] content) are typical for different genera of bacteria. Since TLR-9 recognizes [CG]-containing DNA motifs, it can be speculated that DNA from differen...

Magnesium reduces vascular smooth muscle cell (VSMC) calcification in vitro but the mechanism has not been revealed so far. This work used only slightly increased magnesium levels and aimed at determining: a) whether inhibition of magnesium transport into the cell influences VSMC calcification, b) whether Wnt/β-catenin signaling, a key mediator of osteogenic differentiation, is modified by magnesium and c) whether magnesium can influence already established vascular calcification. Human VSMC incubated with high phosphate (3.3 mM) and moderately elevated magnesium (1.4 mM) significantly reduced VSMC calcification and expression of the osteogenic transcription factors Cbfa-1 and osterix, and up-regulated expression of the natural calcification inhibitors matrix Gla protein (MGP) and osteoprotegerin (OPG). The protective effects of magnesium on calcification and expression of osteogenic markers were no longer observed in VSMC cultured with an inhibitor of cellular magnesium transport (2-aminoethoxy-diphenylborate [2-APB]). High phosphate induced activation of Wnt/β-catenin pathway as demonstrated by the translocation of β-catenin into the nucleus, increased expression of the frizzled-3 gene, and downregulation of Dkk-1 gene, a specific antagonist of the Wnt/β-catenin signaling pathway. The addition of magnesium however inhibited phosphate-induced activation of Wnt/β-catenin signaling pathway. Furthermore, TRPM7 silencing using siRNA resulted in activation of Wnt/β-catenin signaling pathway. Additional experiments were performed to test the ability of magnesium to halt the progression of already established VSMC calcification in vitro. The delayed addition of magnesium decreased calcium content, down-regulated Cbfa-1 and osterix and up-regulated MGP and OPG, when compared with a control group. This effect was not observed when 2-APB was added. In conclusion, magnesium transport through the cell membrane is important to inhibit VSMC calcification in vitro. Inhibition of Wnt/β-catenin by magnesium is one potential intracellular mechanism by which this anti-calcifying effect is achieved.