The tumour-suppressive function of CLU is explained by its localisation and interaction with HSP60

The product of the CLU gene promotes or inhibits tumourigenesis in a context-dependent manner. It has been hypothesised that different CLU isoforms have different and even opposing biological functions, but this theory has not been experimentally validated. Here we show that molecules involved in survival pathways are differentially modulated by the intracellular or secreted forms of CLU. Secreted CLU, which is selectively increased after transformation, activates the survival factor AKT, whereas intracellular CLU inhibits the activity of the oncogenic transcription factor nuclear factor kappa B. Furthermore, intracellular CLU is inactivated by the pro-proliferative and pro-survival activity of the chaperone protein HSP60 in neuroblastoma cells by forming a physical complex. Thus, localisation is key for CLU physiology, explaining the wide range of effects in cell survival and transformation

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth

Search for anomalous Wtb couplings and flavour-changing neutral currents in t-channel single top quark production in pp collisions at root s=7 and 8 TeV

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Search for massive resonances decaying in to WW,WZ or ZZ bosons in proton-proton collisions at root s=13 TeV

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Search for massive resonances in dijet systems containing jets tagged as W or Z boson decays in pp collisions at √s=8 TeV

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Calibration of the CMS Drift Tube Chambers and Measurement of the Drift Velocity with Cosmic Rays

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Measurement of differential cross sections for top quark pair production using the lepton plus jets final state in proton-proton collisions at 13 TeV

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Measurement of the production cross section of a W boson in association with two b jets in pp collisions at root s=8TeV

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