BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT.

The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied whole-genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single-nucleotide polymorphisms (SNPs) in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong linkage disequilibrium between each other (R2 =0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P<0.00001 for BAT2 SNP rs11538264, and P<0.0001 for BAT3 SNP rs10484558), whereas the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs 2.6%, nominal P=1.15 × 10-8; and adjusted P=0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT

Calibration of centre-of-mass energies at LEP 2 for a precise measurement of the W boson mass

The determination of the centre-of-mass energies for all LEP 2 running is presented. Accurate knowledge of these energies is of primary importance to set the absolute energy scale for the measurement of the W boson mass. The beam energy between 80 and 104 GeV is derived from continuous measurements of the magnetic bending field by 16 NMR probes situated in a number of the LEP dipoles. The relationship between the fields measured by the probes and the beam energy is defined in the NMR model, which is calibrated against precise measurements of the average beam energy between 41 and 61 GeV made using the resonant depolarisation technique. The validity of the NMR model is verified by three independent methods: the flux-loop, which is sensitive to the bending field of all the dipoles of LEP; the spectrometer, which determines the energy through measurements of the deflection of the beam in a magnet of known integrated field; and an analysis of the variation of the synchrotron tune with the total RF voltage. To obtain the centre-of-mass energies, corrections are then applied to account for sources of bending field external to the dipoles, and variations in the local beam energy at each interaction point. The relative error on the centre-of-mass energy determination for the majority of LEP 2 running is 1.2 x 10^{-4}, which is sufficiently precise so as not to introduce a dominant uncertainty on the W mass measurement.Comment: 79 pages, 45 figures, submitted to EPJ

Determination of the Accuracy of Wire Position Sensors

An energy spectrometer has been installed in the LEP accelerator to determine the beam energy with a relative accuracy of 10-4. A precisely calibrated bending magnet is flanked by 6 beam position monitors (BPM). The beam energy is determined by measuring the deflection angle of the LEP beams and the integrated bending field. An accuracy of less than 10-6 m on the beam position is necessary to reach the desired accuracy on the LEP beam energy. Capacitive wire positioning sensors are used to determine the relative mounting stability of each BPM and to calibrate the beam position monitors. Two-dimensional sensors are attached to each side of every BPM support and provide a position measurement with respect to two stretched wires mounted on either side of the LEP beam pipe. The fixing points of each wire are monitored by additional reference sensors. The position information is digitised via a multiplexed high accuracy digital voltmeter and read out continuously during LEP operations. Wire position sensor accuracy was tested in the laboratory with a laser interferometer, while relative accuracy tests are performed in the LEP environment. Systematic effects of synchrotron radiation on the wire position sensor performance were studied

Progress on transverse beam profile measurement using the heterodyne near field speckles method at Alba

We present the recent developments of a study aimed at measuring the transverse beam profile using the Heterodyne Near Field Speckles (HNFS) method. The HNFS technique works by illuminating a suspension of Brownian nanoparticles with synchrotron radiation and studying the resulting interference pattern. The transverse coherence of the source, and therefore, under the conditions of validity of the Van Cittert and Zernike theorem, the transverse electron beam size is retrieved from the interference between the transmitted beam and the spherical waves scattered by each nanoparticle. We here describe the fundamentals of this technique, as well as the recent experimental results obtained with 12 keV undulator radiation at the NCD beamline at the ALBA synchrotron. The applicability of such a technique for future accelerators (e.g. CLIC or FCC) is also discussed

Investigations of the LHC Emittance Blow-Up During the 2012 Proton Run

About 30 % of the potential luminosity performance is lost through the different phases of the LHC cycle, mainly due to transverse emittance blow-up. Measuring the emittance growth is a difficult task with high intensity beams and changing energies. Improvements of the LHC transverse profile instrumentation helped to study various effects. A breakdown of the growth through the different phases of the LHC cycle is given as well as a comparison with the data from the LHC experiments for transverse beam size. In 2012 a number of possible sources and remedies have been studied. Among these are intra beam scattering, 50 Hz noise and the effect of the transverse damper gain. The results of the investigations are summarized in this paper. Requirements for transverse profile instrumentation for post LHC long shutdown operation to finally tackle the emittance growth are given as well

Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4+CD25+FOXP3+ Regulatory T-Cells

OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4+CD25+FOXP3+ T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs

Second hematopoietic SCT in patients with thalassemia recurrence following rejection of the first graft

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