Proteolytic processing of human cytomegalovirus glycoprotein B (gpUL55) is mediatedby the human endoprotease furin

AbstractInhibition of endoproteolytic cleavage of glycoprotein B (gB; gpUL55) of human cytomegalovirus was achieved by treatmentof infected fibroblasts with decanoyl peptidyl chloromethyl ketone (decRVKR-CMK), which inhibits the action of cellular subtilisin-like endoproteases with the amino acid recognition motif R × K/R R. Uncleaved gB precusor molecules of 160 kDa that were accumulated were endoglycosidase H resistant, suggesting that correct cellular transport occurred in the presence of the drug. The inhibitor also prevented endoproteolytic gB processing in CV-1 cells infected with a recombinant vaccinia virus-gB construct (VVgB). Evidence for direct involvement of the ubiquitous subtilisin-like endoprotease furin in gB cleavage was obtained from the observation that coinfection of CV-1 cells with WgB and a recombinant vaccinia-human furin construct reestablished endoproteolytic activity which was normally absent late after infection with WgB alone

Design Study of a Superconducting Insertion Quadrupole Magnet for the Large Hadron Collider

The conceptual design study of a high gradient super conducting insertion quadrupole magnet has been carried out in collaboration between KEK and CERN for the Large Hadron Collider (LHC) to be built at CERN. A model magnet design has been optimized to provide a nominal design field gradient of 240 T/m with a bore aperture of 70 mm and an operational field gradient of 225 T/m at 1.9 K under radiation environment with a beam energy deposit of several watts per meter in the superconducting coils. The design and its optimization process are discussed

Test Results of a Variant-Design LHC Twin-Aperture Dipole Magnet

Since 1989, KEK and CERN carried out jointly an experimental program in the frame of the R&D work for the LHC main dipole. The mechanical structure of this design is based on a separate coil/collar and "horizontally split iron" concept. A total of four single aperture and two twin-aperture 1 m long dipole magnets were built. The last twin-aperture magnet was tested at CERN, reaching a maximum field of 9.55 T at 1.9 K. This paper reports the magnet training performance and quench localization at 1.9 K and 4.5 K. The performance as a function of current ramp rate and measurements of the field quality are also reported

Development and Test Results of a low-β\beta Quadrupole Model for the Large Hadron Collider

A 1-m model of the high gradient 70 mm aperture superconducting low-b quadrupoles for the Large Hadron Collider (LHC) has been developed. A field gradient of 250 T/m at 1.9 K has been achieved with a peak field of 10 T in the coil. This paper describes development of the first model magnet and presents the test results

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Observation of B0->pi0pi0

We report the first observation of the decay B0->pi0pi0, using a 253/fb data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e+e- collider. The measured branching fraction is BF(B0->pi0pi0) = {2.32 +0.4-0.5(stat) +0.2-0.3(syst)} x 10^-6, with a significance of 5.8 standard deviations including systematic uncertainties. We also make the first measurement of the direct CP violating asymmetry in this mode.Comment: 6 pages, 2 figures, submitted to ICHEP04, Beijing and Physical Review Letters. v2: a possible pile-up background is checked and a systematic error for it is include