Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection

Epstein-Barr virus (EBV) infects most of the world’s population and is causally associated with several human cancers, but little is known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We have sequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and the first EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents all strains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequenced from one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, defined almost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism (SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. Some T-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive selection, both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombination between strains, which provides a further mechanism for the generation of diversity. Our results provide the first global view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to further understand the genetics of EBV infection

Building a Social Mandate for Climate Action: Lessons from COVID-19

The COVID-19 imposed lockdown has led to a number of temporary environmental side effects (reduced global emissions, cleaner air, less noise), that the climate community has aspired to achieve over a number of decades. However, these benefits have been achieved at a massive cost to welfare and the economy. This commentary draws lessons from the COVID-19 crisis for climate change. It discusses whether there are more sustainable ways of achieving these benefits, as part of a more desirable, low carbon resilient future, in a more planned, inclusive and less disruptive way. In order to achieve this, we argue for a clearer social contract between citizens and the state. We discuss how COVID-19 has demonstrated that behaviours can change abruptly, that these changes come at a cost, that we need a ‘social mandate’ to ensure these changes remain in the long-term, and that science plays an important role in informing this process. We suggest that deliberative engagement mechanisms, such as citizens’ assemblies and juries, could be a powerful way to build a social mandate for climate action post-COVID-19. This would enable behaviour changes to become more accepted, embedded and bearable in the long-term and provide the basis for future climate action

Measuring subjective well-being from a multidimensional and temporal perspective: Italian adaptation of the I COPPE scale

Background: The objective of this study is to present the psychometric and cultural adaptation of the I COPPE scale to the Italian context. The original 21-item I COPPE was developed by Isaac Prilleltensky and colleagues to integrate a multidimensional and temporal perspective into the quantitative assessment of people’s subjective well-being. The scale comprises seven domains (Overall, Interpersonal, Community, Occupation, Psychological, Physical, and Economic well-being), which tap into past, present, and future self-appraisals of well-being. Methods: The Italian adapted version of the I COPPE scale underwent translation and backtranslation procedure. After a pilot study was conducted on a local sample of 683 university students, a national sample of 2432 Italian citizens responded to the final translated version of the I COPPE scale, 772 of whom re-completed the same survey after a period of four months. Respondents from both waves of the national sample were recruited partly through on-line social networks (i.e. Facebook, Twitter, and SurveyMonkey) and partly by university students who had been trained in Computer-Assisted Survey Information Collection. Results: Data were first screened for non-valid cases and tested for multivariate normality and missing data. The correlation matrix revealed highly significant correlation values, ranging from medium to high for nearly all congeneric variables of the I COPPE scale. Results from a series of nested and non-nested model comparisons supported the 7-factor correlated-traits model originally hypothesised, with factor loadings and inter-item reliability ranging from medium to high. In addition, they revealed that the I COPPE scale has strong internal reliability, with composite reliability always higher than .7, satisfactory construct validity, with average variance extracted nearly always higher than .5, and and full strict invariance across time. Conclusions: The Italian adaptation of the I COPPE scale presents appropriate psychometric properties in terms of both validity and reliability, and therefore can be applied to the Italian context. Some limitation and recommendations for future studies are discussed

An Intermediate-mass Black Hole of Over 500 Solar Masses in the Galaxy ESO 243-49

Ultra-luminous X-ray sources are extragalactic objects located outside the nucleus of the host galaxy with bolometric luminosities >10^39 erg s^-1. These extreme luminosities - if the emission is isotropic and below the theoretical (i.e. Eddington) limit, where the radiation pressure is balanced by the gravitational pressure - imply the presence of an accreting black hole with a mass of ~10^2-10^5 times that of the Sun. The existence of such intermediate mass black holes is in dispute, and though many candidates have been proposed, none are widely accepted as definitive. Here we report the detection of a variable X-ray source with a maximum 0.2-10 keV luminosity of up to 1.2 x 10^42 erg s^-1 in the edge-on spiral galaxy ESO 243-49, with an implied conservative lower limit of the mass of the black hole of ~500 Msun. This finding presents the strongest observational evidence to date for the existence of intermediate mass black holes, providing the long sought after missing link between the stellar mass and super-massive black hole populations.Comment: 5 pages, 2 figures, 1 table, published in Natur

E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia

In common with other E2F1 responsive genes such as p14ARF and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one