IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis

CNS-resident cells, in particular microglia and macrophages, are a source of inflammatory cytokines during inflammation within the CNS. Expression of IL-23, a recently discovered cytokine, has been shown to be critical for the development of experimental autoimmune encephalomyelitis (EAE) in mice. Expression of the p40 subunit of IL-12 and IL-23 by microglia has been shown in situ and in vitro, but direct evidence for a functional significance of p40 expression by CNS cells during an immune response in vivo is still lacking. Here we report that p40 plays a critical role in maintaining encephalitogenicity during the disease course. By using irradiation bone marrow chimeras, we have generated mice in which p40 is deleted from the CNS parenchyma but not the systemic immune compartment. Our studies show that p40 expressed by CNS-endogenous cells is critical for the development of myelin oligodendrocyte glycoprotein-induced EAE. In spite of the reduced clinical disease, the absence of p40 from the CNS has little impact on the degree of inflammation. Expression profiles of the CNS lesions show an increase in Th2 cytokines when compared with mice that develop EAE in the presence of CNS IL-12 and/or IL-23. Taken together, our data demonstrate that p40 expression by CNS-resident cells forms the basis for the Th1 bias of the CNS

The oxygen-independent metabolism of cyclic monoterpenes in Castellaniella defragrans 65Phen

BACKGROUND: The facultatively anaerobic betaproteobacterium Castellaniella defragrans 65Phen utilizes acyclic, monocyclic and bicyclic monoterpenes as sole carbon source under oxic as well as anoxic conditions. A biotransformation pathway of the acyclic β-myrcene required linalool dehydratase-isomerase as initial enzyme acting on the hydrocarbon. An in-frame deletion mutant did not use myrcene, but was able to grow on monocyclic monoterpenes. The genome sequence and a comparative proteome analysis together with a random transposon mutagenesis were conducted to identify genes involved in the monocyclic monoterpene metabolism. Metabolites accumulating in cultures of transposon and in-frame deletion mutants disclosed the degradation pathway. RESULTS: Castellaniella defragrans 65Phen oxidizes the monocyclic monoterpene limonene at the primary methyl group forming perillyl alcohol. The genome of 3.95 Mb contained a 70 kb genome island coding for over 50 proteins involved in the monoterpene metabolism. This island showed higher homology to genes of another monoterpene-mineralizing betaproteobacterium, Thauera terpenica 58Eu(T), than to genomes of the family Alcaligenaceae, which harbors the genus Castellaniella. A collection of 72 transposon mutants unable to grow on limonene contained 17 inactivated genes, with 46 mutants located in the two genes ctmAB (cyclic terpene metabolism). CtmA and ctmB were annotated as FAD-dependent oxidoreductases and clustered together with ctmE, a 2Fe-2S ferredoxin gene, and ctmF, coding for a NADH:ferredoxin oxidoreductase. Transposon mutants of ctmA, B or E did not grow aerobically or anaerobically on limonene, but on perillyl alcohol. The next steps in the pathway are catalyzed by the geraniol dehydrogenase GeoA and the geranial dehydrogenase GeoB, yielding perillic acid. Two transposon mutants had inactivated genes of the monoterpene ring cleavage (mrc) pathway. 2-Methylcitrate synthase and 2-methylcitrate dehydratase were also essential for the monoterpene metabolism but not for growth on acetate. CONCLUSIONS: The genome of Castellaniella defragrans 65Phen is related to other genomes of Alcaligenaceae, but contains a genomic island with genes of the monoterpene metabolism. Castellaniella defragrans 65Phen degrades limonene via a limonene dehydrogenase and the oxidation of perillyl alcohol. The initial oxidation at the primary methyl group is independent of molecular oxygen

On the Structure of Infrared Singularities of Gauge-Theory Amplitudes

A closed formula is obtained for the infrared singularities of dimensionally regularized, massless gauge-theory scattering amplitudes with an arbitrary number of legs and loops. It follows from an all-order conjecture for the anomalous-dimension matrix of n-jet operators in soft-collinear effective theory. We show that the form of this anomalous dimension is severely constrained by soft-collinear factorization, non-abelian exponentiation, and the behavior of amplitudes in collinear limits. Using a diagrammatic analysis, we demonstrate that these constraints imply that to three-loop order the anomalous dimension involves only two-parton correlations, with the possible exception of a single color structure multiplying a function of conformal cross ratios depending on the momenta of four external partons, which would have to vanish in all two-particle collinear limits. We argue that such a function does not appear at three-loop order, and that the same is true in higher orders. Our formula predicts Casimir scaling of the cusp anomalous dimension to all orders in perturbation theory, and we explicitly check that the constraints exclude the appearance of higher Casimir invariants at four loops. Using known results for the quark and gluon form factors, we derive the three-loop coefficients of the 1/epsilon^n pole terms (with n=1,...,6) for an arbitrary n-parton scattering amplitude in massless QCD. This generalizes Catani's two-loop formula proposed in 1998.Comment: 46 pages, 9 figures; v2: improved treatment of collinear limits, references added; v3: improved discussion of non-abelian exponentiation, references updated; v4: typo in eq. (17) fixed, references updated; v5: additional term in (17

Chromosomal Gains and Losses in Uveal Melanomas Detected by Comparative Genomic Hybridization

Eleven uveal melanomas were analyzed using comparative genomic hybridization (CGH). The most abundant genetic changes were loss of chromosome 3, overrepresentation of 6p, loss of 6q, and multiplication of 8q. The smallest overrepresented regions on 6p and 8q were 6pterp21 and 8q24qter, respectively. Several additional gains and losses of chromosome segments were repeatedly observed, the most frequent one being loss of 9p (three cases). Monosomy 3 appeared to be a marker for ciliary body involvement. CGH data were compared with the results of chromosome banding. Some alterations, e.g., gains of 6p and losses of 6q, were observed with higher frequencies after CGH, while others, e.g., 9p deletions, were detected only by CGH. The data suggest some similarities of cytogenetic alterations between cutaneous and uveal melanoma. In particular, the 9p deletions are of interest due to recent reports about the location of a putative tumor-suppressor gene for cutaneous malignant melanoma in this region

The relativistic self-energy in nuclear dynamics

It is a well known fact that Dirac phenomenology of nuclear forces predicts the existence of large scalar and vector mean fields in matter. To analyse the relativistic self-energy in a model independent way, modern high precision nucleon-nucleon ($NN$) potentials are mapped on a relativistic operator basis using projection techniques. This allows to compare the various potentials at the level of covariant amplitudes were a remarkable agreement is found. It allows further to calculate the relativistic self-energy in nuclear matter in Hartree-Fock approximation. Independent of the choice of the nucleon-nucleon interaction large scalar and vector mean fields of several hundred MeV magnitude are generated at tree level. In the framework of chiral EFT these fields are dominantly generated by contact terms which occur at next-to-leading order in the chiral expansion. Consistent with Dirac phenomenology the corresponding low energy constants which generate the large fields are closely connected to the spin-orbit interaction in $NN$ scattering. The connection to QCD sum rules is discussed as well.Comment: 49 pages, 13 figure

Electroweak Gauge-Boson Production at Small q_T: Infrared Safety from the Collinear Anomaly

Using methods from effective field theory, we develop a novel, systematic framework for the calculation of the cross sections for electroweak gauge-boson production at small and very small transverse momentum q_T, in which large logarithms of the scale ratio M_V/q_T are resummed to all orders. These cross sections receive logarithmically enhanced corrections from two sources: the running of the hard matching coefficient and the collinear factorization anomaly. The anomaly leads to the dynamical generation of a non-perturbative scale q_* ~ M_V e^{-const/\alpha_s(M_V)}, which protects the processes from receiving large long-distance hadronic contributions. Expanding the cross sections in either \alpha_s or q_T generates strongly divergent series, which must be resummed. As a by-product, we obtain an explicit non-perturbative expression for the intercept of the cross sections at q_T=0, including the normalization and first-order \alpha_s(q_*) correction. We perform a detailed numerical comparison of our predictions with the available data on the transverse-momentum distribution in Z-boson production at the Tevatron and LHC.Comment: 34 pages, 9 figure

Step-wedge cluster-randomised community-based trials: An application to the study of the impact of community health insurance

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.BACKGROUND: We describe a step-wedge cluster-randomised community-based trial which has been conducted since 2003 to accompany the implementation of a community health insurance (CHI) scheme in West Africa. The trial aims at overcoming the paucity of evidence-based information on the impact of CHI. Impact is defined in terms of changes in health service utilisation and household protection against the cost of illness. Our exclusive focus on the description and discussion of the methods is justified by the fact that the study relies on a methodology previously applied in the field of disease control, but never in the field of health financing. METHODS: First, we clarify how clusters were defined both in respect of statistical considerations and of local geographical and socio-cultural concerns. Second, we illustrate how households within clusters were sampled. Third, we expound the data collection process and the survey instruments. Finally, we outline the statistical tools to be applied to estimate the impact of CHI. CONCLUSION: We discuss all design choices both in relation to methodological considerations and to specific ethical and organisational concerns faced in the field. On the basis of the appraisal of our experience, we postulate that conducting relatively sophisticated trials (such as our step-wedge cluster-randomised community-based trial) aimed at generating sound public health evidence, is both feasible and valuable also in low income settings. Our work shows that if accurately designed in conjunction with local health authorities, such trials have the potential to generate sound scientific evidence and do not hinder, but at times even facilitate, the implementation of complex health interventions such as CHI

Nucleon mass and pion loops: Renormalization

Using Dyson--Schwinger equations, the nucleon propagator is analyzed nonperturbatively in a field--theoretical model for the pion--nucleon interaction. Infinities are circumvented by using pion--nucleon form factors which define the physical scale. It is shown that the correct, finite, on--shell nucleon renormalization is important for the value of the mass--shift and the propagator. For physically acceptable forms of the pion--nucleon form factor the rainbow approximation together with renormalization is inconsistent. Going beyond the rainbow approximation, the full pion--nucleon vertex is modelled by its bare part plus a one--loop correction including an effective $\Delta$. It is found that a consistent value for the nucleon mass--shift can be obtained as a consequence of a subtle interplay between wave function and vertex renormalization. Furthermore, the bare and renormalized pion--nucleon coupling constant are approximately equal, consistent with results from the Cloudy Bag Model.Comment: 14 pages, 6 figure

Coupling a single atomic quantum bit to a high finesse optical cavity

The quadrupole S$_{1/2}$ -- D$_{5/2}$ optical transition of a single trapped Ca$^+$ ion, well suited for encoding a quantum bit of information, is coherently coupled to the standing wave field of a high finesse cavity. The coupling is verified by observing the ion's response to both spatial and temporal variations of the intracavity field. We also achieve deterministic coupling of the cavity mode to the ion's vibrational state by selectively exciting vibrational state-changing transitions and by controlling the position of the ion in the standing wave field with nanometer-precision

πΞ\pi\Xi phase shifts and CP Violation in Ω→πΞ{\Omega\to\pi\Xi} Decay

In the study of CP violation signals in {\O}\to\pi\Xi nonleptonic decays, the strong $J$=3/2 $P$ and $D$ phase shifts for the $\pi\Xi$ final-state interactions are needed. These phases are calculated using an effective Lagrangian model, including $\Xi$, $\Xi^*$(1530), $\rho$ and the $\sigma$-term, in the intermediate states. The $\sigma$-term is calculated in terms of the scalar form factor of the baryon.Comment: 6 pages, 2 figure