Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies

The ALICE silicon pixel detector read-out electronics

The ALICE silicon pixel detector (SPD) constitutes the two innermost layers of the ALICE inner tracker system. The SPD contains 10 million pixels segmented in 120 detector modules (half staves), which are connected to the offdetector electronics with bidirectional optical links. Raw data from the on-detector electronics are sent to 20 FPGA-based processor cards (Routers) each carrying three 2-channel linkreceiver daughter-cards. The routers process the data and send them to the ALICE DAQ system via the ALICE detector data link (DDL). The SPD control, configuration and data monitoring is performed via the VME interface of the routers. This paper describes the detector readout and control via the off-detector electronics

Synthetic Aβ peptides acquire prion-like properties in the brain

In transmission studies with Alzheimer's disease (AD) animal models, the formation of Aβ plaques is proposed to be initiated by seeding the inoculated amyloid β (Aβ) peptides in the brain. Like the misfolded scrapie prion protein (PrP(Sc)) in prion diseases, Aβ in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aβ remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aβ peptides and Aβ isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aβ species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aβ immunoreactivity after digestion with PK. In contrast, synthetic Aβ40 and Aβ42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aβ40 and Aβ42 synthetic peptides shows that both species of Aβ form mature fibrils. Those generated from Aβ40 are longer but less numerous than those made of Aβ42. When spiked into human brain homogenates, both Aβ40 and Aβ42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aβ peptides PrP(Sc)-like physicochemical properties

Performance of ALICE pixel prototypes in high energy beams

The two innermost layers of the ALICE inner tracking system are instrumented with silicon pixel detectors. Single chip assembly prototypes of the ALICE pixels have been tested in high energy particle beams at the CERN SPS. Detection efficiency and spatial precision have been studied as a function of the threshold and the track incidence angle. The experimental method, data analysis and main results are presented.Comment: 10 pages, 9 figures, contribution to PIX2005 Workshop, Bonn (Germany), 5-8 September 200

Beam Test Performance and Simulation of Prototypes for the ALICE Silicon Pixel Detector

The silicon pixel detector (SPD) of the ALICE experiment in preparation at the Large Hadron Collider (LHC) at CERN is designed to provide the precise vertex reconstruction needed for measuring heavy flavor production in heavy ion collisions at very high energies and high multiplicity. The SPD forms the innermost part of the Inner Tracking System (ITS) which also includes silicon drift and silicon strip detectors. Single assembly prototypes of the ALICE SPD have been tested at the CERN SPS using high energy proton/pion beams in 2002 and 2003. We report on the experimental determination of the spatial precision. We also report on the first combined beam test with prototypes of the other ITS silicon detector technologies at the CERN SPS in November 2004. The issue of SPD simulation is briefly discussed.Comment: 4 pages, 5 figures, prepared for proceedings of 7th International Position Sensitive Detectors Conference, Liverpool, Sept. 200

Run 2 Upgrades to the CMS Level-1 Calorimeter Trigger

The CMS Level-1 calorimeter trigger is being upgraded in two stages to maintain performance as the LHC increases pile-up and instantaneous luminosity in its second run. In the first stage, improved algorithms including event-by-event pile-up corrections are used. New algorithms for heavy ion running have also been developed. In the second stage, higher granularity inputs and a time-multiplexed approach allow for improved position and energy resolution. Data processing in both stages of the upgrade is performed with new, Xilinx Virtex-7 based AMC cards.Comment: 10 pages, 7 figure