3,480 research outputs found
Design of a Base-Board for arrays of closely-packed Multi-Anode Photo-Multipliers
We describe the design of a Base-Board to house Multi-Anode Photo-Multipliers
for use in large-area arrays of light sensors. The goals, the design, the
results of tests on the prototypes and future developments are presented.Comment: 16 pages, 5 figures, submitted to Nucl. Instrum. and Meth.
Quantitative system drift compensates for altered maternal inputs to the gap gene network of the scuttle fly Megaselia abdita.
Published onlineJournal ArticleThis is the final version of the article. Available from eLife Sciences Publications via the DOI in this record.The segmentation gene network in insects can produce equivalent phenotypic outputs despite differences in upstream regulatory inputs between species. We investigate the mechanistic basis of this phenomenon through a systems-level analysis of the gap gene network in the scuttle fly Megaselia abdita (Phoridae). It combines quantification of gene expression at high spatio-temporal resolution with systematic knock-downs by RNA interference (RNAi). Initiation and dynamics of gap gene expression differ markedly between M. abdita and Drosophila melanogaster, while the output of the system converges to equivalent patterns at the end of the blastoderm stage. Although the qualitative structure of the gap gene network is conserved, there are differences in the strength of regulatory interactions between species. We term such network rewiring 'quantitative system drift'. It provides a mechanistic explanation for the developmental hourglass model in the dipteran lineage. Quantitative system drift is likely to be a widespread mechanism for developmental evolution.Ministerio de Economía y Competitividad MEC/EMBL Agreement/ BFU2009-10184/ BFU2012-33775/
SEV-2012-0208
Agència de Gestió d'Ajuts Universitaris I de Recerca SGR Grant 406
European Commission FP7-KBBE-2011-5/289434
National Science Foundation IOS-0719445/IOS-112121
The LHCb RICH upgrade for the high luminosity LHC era
The hadron particle identification provided by the RICH system in LHCb over a momentum range of 2.6–100 GeV/c has been a key element of the success of the experiment and will remain equally important for Upgrade II. With luminosities expected up to 7.5 times those expected for Upgrade I and 75 times those realised in the past, maintaining the current excellent particle identification performance demands a substantial improvement in the precision of the measurements of the space and time coordinates of the photons detected in the RICH. It will require a readout strategy with high-resolution timing information and making significant improvements in the resolution of the reconstructed Cherenkov angle
A phorbol ester response element within the human T-cell receptor beta-chain enhancer.
Runx1 orchestrates sphingolipid metabolism and glucocorticoid resistance in lymphomagenesis
The three-membered RUNX gene family includes RUNX1, a major mutational target in human leukemias, and displays hallmarks of both tumour suppressors and oncogenes. In mouse models the Runx genes appear to act as conditional oncogenes, as ectopic expression is growth suppressive in normal cells but drives lymphoma development potently when combined with over-expressed Myc or loss of p53. Clues to underlying mechanisms emerged previously from murine fibroblasts where ectopic expression of any of the Runx genes promotes survival through direct and indirect regulation of key enzymes in sphingolipid metabolism associated with a shift in the ‘sphingolipid rheostat’ from ceramide to sphingosine-1-phosphate (S1P). Testing of this relationship in lymphoma cells was therefore a high priority. We find that ectopic expression of Runx1 in lymphoma cells consistently perturbs the sphingolipid rheostat, while an essential physiological role for Runx1 is revealed by reduced S1P levels in normal spleen after partial Cre-mediated excision. Furthermore we show that ectopic Runx1 expression confers increased resistance of lymphoma cells to glucocorticoid-mediated apoptosis, and elucidate the mechanism of cross-talk between glucocorticoid and sphingolipid metabolism through Sgpp1. Dexamethasone potently induces expression of Sgpp1 in T-lymphoma cells and drives cell death which is reduced by partial knockdown of Sgpp1 with shRNA or direct transcriptional repression of Sgpp1 by ectopic Runx1. Together these data show that Runx1 plays a role in regulating the sphingolipid rheostat in normal development and that perturbation of this cell fate regulator contributes to Runx-driven lymphomagenesis
Test of the photon detection system for the LHCb RICH Upgrade in a charged particle beam
The LHCb detector will be upgraded to make more efficient use of the
available luminosity at the LHC in Run III and extend its potential for
discovery. The Ring Imaging Cherenkov detectors are key components of the LHCb
detector for particle identification. In this paper we describe the setup and
the results of tests in a charged particle beam, carried out to assess
prototypes of the upgraded opto-electronic chain from the Multi-Anode PMT
photosensor to the readout and data acquisition system.Comment: 25 pages, 22 figure
Human Polycomb 2 Protein Is a SUMO E3 Ligase and Alleviates Substrate-Induced Inhibition of Cystathionine β-Synthase Sumoylation
Human cystathionine β-synthase (CBS) catalyzes the first irreversible
step in the transsulfuration pathway and commits homocysteine to the synthesis
of cysteine. Mutations in CBS are the most common cause of severe hereditary
hyperhomocysteinemia. A yeast two-hybrid approach to screen for proteins that
interact with CBS had previously identified several components of the
sumoylation pathway and resulted in the demonstration that CBS is a substrate
for sumoylation. In this study, we demonstrate that sumoylation of CBS is
enhanced in the presence of human polycomb group protein 2 (hPc2), an
interacting partner that was identified in the initial yeast two-hybrid screen.
When the substrates for CBS, homocysteine and serine for cystathionine
generation and homocysteine and cysteine for H2S generation, are
added to the sumoylation mixture, they inhibit the sumoylation reaction, but
only in the absence of hPc2. Similarly, the product of the CBS reaction,
cystathionine, inhibits sumoylation in the absence of hPc2. Sumoylation in turn
decreases CBS activity by ∼28% in the absence of hPc2 and by
70% in its presence. Based on these results, we conclude that hPc2
serves as a SUMO E3 ligase for CBS, increasing the efficiency of sumoylation. We
also demonstrate that γ-cystathionase, the second enzyme in the
transsulfuration pathway is a substrate for sumoylation under in vitro
conditions. We speculate that the role of this modification may be for nuclear
localization of the cysteine-generating pathway under conditions where nuclear
glutathione demand is high
ChPT tests at the NA48 and NA62 experiments at CERN
The NA48/2 Collaboration at CERN has accumulated unprecedented statistics of
rare kaon decays in the Ke4 modes: Ke4(+-) ()
and Ke4(00) () with nearly one percent
background contamination. The detailed study of form factors and branching
rates, based on these data, has been completed recently. The results brings new
inputs to low energy strong interactions description and tests of Chiral
Perturbation Theory (ChPT) and lattice QCD calculations. In particular, new
data support the ChPT prediction for a cusp in the invariant mass
spectrum at the two charged pions threshold for Ke4(00) decay. New final
results from an analysis of about 400 rare
decay candidates collected by the NA48/2 and NA62 experiments at CERN during
low intensity runs with minimum bias trigger configurations are presented. The
results include a model-independent decay rate measurement and fits to ChPT
description.Comment: XIIth International Conference on Heavy Quarks and Leptons 2014,
Mainz, German
Recent NA48/2 and NA62 results
The NA48/2 Collaboration at CERN has accumulated and analysed unprecedented
statistics of rare kaon decays in the modes: () and ()
with nearly one percent background contamination. It leads to the improved
measurement of branching fractions and detailed form factor studies. New final
results from the analysis of 381 rare decay
candidates collected by the NA48/2 and NA62 experiments at CERN are presented.
The results include a decay rate measurement and fits to Chiral Perturbation
Theory (ChPT) description.Comment: Prepared for the Proceedings of "Moriond QCD and High Energy
Interactions. March 22-29 2014." conferenc
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