Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

The symmetry of M-theories

We consider the Cartan subalgebra of any very extended algebra Script G+++ where Script G is a simple Lie algebra and let the parameters be space-time fields. These are identified with diagonal metrics and dilatons. Using the properties of the algebra, we find that for all very extensions Script G+++ of simple Lie algebras there are theories of gravity and matter, which admit classical solutions carrying representations of the Weyl group of Script G+++. We also identify the T and S-dualities of superstrings and of the bosonic string with Weyl reflections and outer automorphisms of well-chosen very extended algebras and we exhibit specific features of the very extensions. We take these results as indication that very extended algebras underlie symmetries of any consistent theory of gravity and matter, and might encode basic information for the construction of such theory

JET experiments with tritium and deuterium–tritium mixtures

Extensive preparations are now underway for an experiment in the Joint European Torus (JET) using tritium and deuterium–tritium mixtures. The goals of this experiment are described as well as the progress that has been made in developing plasma operational scenarios and physics reference pulses for use in deuterium–tritium and full tritium plasmas. At present, the high performance plasmas to be tested with tritium are based on either a conventional ELMy H-mode at high plasma current and magnetic field (operation at up to 4 MA and 4 T is being prepared) or the so-called improved H-mode or hybrid regime of operation in which high normalised plasma pressure at somewhat reduced plasma current results in enhanced energy confinement. Both of these regimes are being re-developed in conjunction with JET's ITER-like Wall (ILW) of beryllium and tungsten. The influence of the ILW on plasma operation and performance has been substantial. Considerable progress has been made on optimising performance with the all-metal wall. Indeed, operation at the (normalised) ITER reference confinement and pressure has been re-established in JET albeit not yet at high current. In parallel with the physics development, extensive technical preparations are being made to operate JET with tritium. The state and scope of these preparations is reviewed, including the work being done on the safety case for DT operation and on upgrading machine infrastructure and diagnostics. A specific example of the latter is the planned calibration at 14 MeV of JET neutron diagnostics

ITER-like antenna capacitors voltage probes: Circuit/electromagnetic calculations and calibrations

The analyses illustrated in this manuscript have been performed in order to provide the required data for the amplitude-and-phase calibration of the D-dot voltage probes used in the ITER-like antenna at the Joint European Torus tokamak. Their equivalent electrical circuit has been extracted and analyzed, and it has been compared to the one of voltage probes installed in simple transmission lines. A radio-frequency calibration technique has been formulated and exact mathematical relations have been derived. This technique mixes in an elegant fashion data extracted from measurements and numerical calculations to retrieve the calibration factors. The latter have been compared to previous calibration data with excellent agreement proving the robustness of the proposed radio-frequency calibration technique. In particular, it has been stressed that it is crucial to take into account environmental parasitic effects. A low-frequency calibration technique has been in addition formulated and analyzed in depth. The equivalence between the radio-frequency and low-frequency techniques has been rigorously demonstrated. The radio-frequency calibration technique is preferable in the case of the ITER-like antenna due to uncertainties on the characteristics of the cables connected at the inputs of the voltage probes. A method to extract the effect of a mismatched data acquisition system has been derived for both calibration techniques. Finally it has been outlined that in the case of the ITER-like antenna voltage probes can be in addition used to monitor the currents at the inputs of the antenna