Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

Search for CP Violation in the Decay Z -> b (b bar) g

About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z -> b \bar{b} g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, ${\hat{h}}_b = {\hat{h}}_{Ab}g_{Vb}-{\hat{h}}_{Vb}g_{Ab}$ and $h^{\ast}_b = \sqrt{\hat{h}_{Vb}^{2}+\hat{h}_{Ab}^{2}}$, limits of \hat{h}_b < 0.59$and$h^{\ast}_{b} < 3.02$ are given at 95\% CL.Comment: 8 pages, 1 postscript figure, uses here.sty, epsfig.st

The large area detector onboard the eXTP mission

The Large Area Detector (LAD) is the high-throughput, spectral-timing instrument onboard the eXTP mission, a flagship mission of the Chinese Academy of Sciences and the China National Space Administration, with a large European participation coordinated by Italy and Spain. The eXTP mission is currently performing its phase B study, with a target launch at the end-2027. The eXTP scientific payload includes four instruments (SFA, PFA, LAD and WFM) offering unprecedented simultaneous wide-band X-ray timing and polarimetry sensitivity. The LAD instrument is based on the design originally proposed for the LOFT mission. It envisages a deployed 3.2 m2 effective area in the 2-30 keV energy range, achieved through the technology of the large-area Silicon Drift Detectors - offering a spectral resolution of up to 200 eV FWHM at 6 keV - and of capillary plate collimators - limiting the field of view to about 1 degree. In this paper we will provide an overview of the LAD instrument design, its current status of development and anticipated performance

Production of excited beauty states in Z decays

A data sample of about 3.0 million hadronic Z decays collected by the ALEPH experiment at LEP in the years 1991 through 1994, is used to make an inclusive selection of B~hadron events. In this event sample 4227 \pm 140 \pm 252 B^* mesons in the decay B^* \to B \gamma and 1944 \pm 108 \pm 161 B^{**} mesons decaying into a B~meson and a charged pion are reconstructed. For the well established B^* meson the following quantities areobtained: \Delta M = M_{B^*} - M_{B} = (45.30\pm 0.35\pm 0.87)~\mathrm{MeV}/c^2 and N_{B^*}/(N_B+N_{B^*}) = (77.1 \pm 2.6 \pm 7.0)\%. The angular distribution of the photons in the B^* rest frame is used to measure the relative contribution of longitudinal B^* polarization states to be \sigma_L/(\sigma_L + \sigma_T)= (33 \pm 6 \pm 5)\%. \\ Resonance structure in the M(B\pi)-M(B) mass difference is observed at (424 \pm 4 \pm 10)~\mathrm{MeV}/c^2. Its shape and position is in agreement with the expectation for B^{**}_{u,d} states decaying into B_{u,d}^{(*)} \pi^\pm. The signal is therefore interpreted as arising from them. The relative production rate is determined to be \frac{BR(Z \to b \to B_{u,d}^{**})}{BR(Z \to b \to B_{u,d})} = [27.9 \pm 1.6(stat) \pm 5.9(syst) \phantom{a}^{+3.9}_{-5.6}(model)]\%. where the third error reflects the uncertainty due to different production and decay models for the broad B_{u,d}^{**} states

Tau hadronic branching ratios

From 64492 selected \tau-pair events, produced at the Z^0 resonance, the measurement of the tau decays into hadrons from a global analysis using 1991, 1992 and 1993 ALEPH data is presented. Special emphasis is given to the reconstruction of photons and \pi^0's, and the removal of fake photons. A detailed study of the systematics entering the \pi^0 reconstruction is also given. A complete and consistent set of tau hadronic branching ratios is presented for 18 exclusive modes. Most measurements are more precise than the present world average. The new level of precision reached allows a stringent test of \tau-\mu universality in hadronic decays, g_\tau/g_\mu \ = \ 1.0013 \ \pm \ 0.0095, and the first measurement of the vector and axial-vector contributions to the non-strange hadronic \tau decay width: R_{\tau ,V} \ = \ 1.788 \ \pm \ 0.025 and R_{\tau ,A} \ = \ 1.694 \ \pm \ 0.027. The ratio (R_{\tau ,V} - R_{\tau ,A}) / (R_{\tau ,V} + R_{\tau ,A}), equal to (2.7 \pm 1.3) \ \%, is a measure of the importance of QCD non-perturbative contributions to the hadronic \tau decay widt

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008