EAPP: Gatekeeper at the crossroad of apoptosis and p21-mediated cell-cycle arrest

We previously identified and characterized E2F-associated phospho-protein (EAPP), a nuclear phosphoprotein that interacts with the activating members of the E2F transcription factor family. EAPP levels are frequently elevated in transformed human cells. To examine the biological relevance of EAPP, we studied its properties in stressed and unstressed cells. Overexpression of EAPP in U2OS cells increased the fraction of G1 cells and lead to heightened resistance against DNA damage- or E2F1-induced apoptosis in a p21-dependent manner. EAPP itself becomes upregulated in confluent cells and after DNA damage and stimulates the expression of p21 independently of p53. It binds to the p21 promoter and seems to be required for the assembly of the transcription initiation complex. RNAi-mediated knockdown of EAPP expression brought about increased sensitivity towards DNA damage and resulted in apoptosis even in the absence of stress. Our results indicate that the level of EAPP is critical for cellular homeostasis. Too much of it results in G1 arrest and resistance to apoptosis, which, paradoxically, might favor cellular transformation. Too little EAPP seems to retard the expression not only of the p21 gene, but also of a number of other genes and ultimately results in apoptosis

Towards a public policy of cities and human settlements in the 21st century

Cities and other human settlements are major contributors to climate change and are highly vulnerable to its impacts. They are also uniquely positioned to reduce greenhouse gas emissions and lead adaptation efforts. These compound challenges and opportunities require a comprehensive perspective on the public policy of human settlements. Drawing on core literature that has driven debate around cities and climate over recent decades, we put forward a set of boundary objects that can be applied to connect the knowledge of epistemic communities and support an integrated urbanism. We then use these boundary objects to develop the Goals-Intervention-Stakeholder-Enablers (GISE) framework for a public policy of human settlements that is both place-specific and provides insights and tools useful for climate action in cities and other human settlements worldwide. Using examples from Berlin, we apply this framework to show that climate mitigation and adaptation, public health, and well-being goals are closely linked and mutually supportive when a comprehensive approach to urban public policy is applied

Radiation hardness qualification of PbWO4 scintillation crystals for the CMS Electromagnetic Calorimeter

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2010 IOPEnsuring the radiation hardness of PbWO4 crystals was one of the main priorities during the construction of the electromagnetic calorimeter of the CMS experiment at CERN. The production on an industrial scale of radiation hard crystals and their certification over a period of several years represented a difficult challenge both for CMS and for the crystal suppliers. The present article reviews the related scientific and technological problems encountered

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

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

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

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

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere