Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.
Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.
Inclusive jet production in pPb collisions at a nucleon-nucleon (NN) center-of-mass energy of [Formula: see text] is studied with the CMS detector at the LHC. A data sample corresponding to an integrated luminosity of 30.1 nb[Formula: see text] is analyzed. The jet transverse momentum spectra are studied in seven pseudorapidity intervals covering the range [Formula: see text] in the NN center-of-mass frame. The jet production yields at forward and backward pseudorapidity are compared and no significant asymmetry about [Formula: see text] is observed in the measured kinematic range. The measurements in the pPb system are compared to reference jet spectra obtained by extrapolation from previous measurements in pp collisions at [Formula: see text]. In all pseudorapidity ranges, nuclear modifications in inclusive jet production are found to be small, as predicted by next-to-leading order perturbative QCD calculations that incorporate nuclear effects in the parton distribution functions.
Results are reported from a search for the pair production of top squarks, the supersymmetric partners of top quarks, in final states with jets and missing transverse momentum. The data sample used in this search was collected by the CMS detector and corresponds to an integrated luminosity of 18.9[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8[Formula: see text] produced by the LHC. The search features novel background suppression and prediction methods, including a dedicated top quark pair reconstruction algorithm. The data are found to be in agreement with the predicted backgrounds. Exclusion limits are set in simplified supersymmetry models with the top squark decaying to jets and an undetected neutralino, either through a top quark or through a bottom quark and chargino. Models with the top squark decaying via a top quark are excluded for top squark masses up to 755[Formula: see text] in the case of neutralino masses below 200[Formula: see text]. For decays via a chargino, top squark masses up to 620[Formula: see text] are excluded, depending on the masses of the chargino and neutralino.
A measurement of the double-differential inclusive jet cross section as a function of jet transverse momentum [Formula: see text] and absolute jet rapidity [Formula: see text] is presented. The analysis is based on proton-proton collisions collected by the CMS experiment at the LHC at a centre-of-mass energy of 13[Formula: see text]. The data samples correspond to integrated luminosities of 71 and 44[Formula: see text] for [Formula: see text] and [Formula: see text], respectively. Jets are reconstructed with the anti-[Formula: see text] clustering algorithm for two jet sizes, R, of 0.7 and 0.4, in a phase space region covering jet [Formula: see text] up to 2[Formula: see text] and jet rapidity up to [Formula: see text] = 4.7. Predictions of perturbative quantum chromodynamics at next-to-leading order precision, complemented with electroweak and nonperturbative corrections, are used to compute the absolute scale and the shape of the inclusive jet cross section. The cross section difference in R, when going to a smaller jet size of 0.4, is best described by Monte Carlo event generators with next-to-leading order predictions matched to parton showering, hadronisation, and multiparton interactions. In the phase space accessible with the new data, this measurement provides a first indication that jet physics is as well understood at [Formula: see text] as at smaller centre-of-mass energies.
A search for a massive resonance [Formula: see text]decaying into a W and a Higgs boson in the [Formula: see text] ([Formula: see text], [Formula: see text]) final state is presented. Results are based on data corresponding to an integrated luminosity of 19.7[Formula: see text] of proton-proton collisions at [Formula: see text] [Formula: see text], collected using the CMS detector at the LHC. For a high-mass ([Formula: see text]1[Formula: see text]) resonance, the two bottom quarks coming from the Higgs boson decay are reconstructed as a single jet, which can be tagged by placing requirements on its substructure and flavour. Exclusion limits at 95 % confidence level are set on the production cross section of a narrow resonance decaying into WH, as a function of its mass. In the context of a little Higgs model, a lower limit on the [Formula: see text] mass of 1.4[Formula: see text] is set. In a heavy vector triplet model that mimics the properties of composite Higgs models, a lower limit on the [Formula: see text] mass of 1.5[Formula: see text] is set. In the context of this model, the results are combined with related searches to obtain a lower limit on the [Formula: see text] mass of 1.8[Formula: see text], the most restrictive to date for decays to a pair of standard model bosons.
Jet multiplicity distributions in top quark pair ([Formula: see text]) events are measured in pp collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC using a data set corresponding to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton decay channels ([Formula: see text], [Formula: see text], and [Formula: see text]). The absolute and normalized differential cross sections for [Formula: see text] production are measured as a function of the jet multiplicity in the event for different jet transverse momentum thresholds and the kinematic properties of the leading additional jets. The differential [Formula: see text] and [Formula: see text] cross sections are presented for the first time as a function of the kinematic properties of the leading additional [Formula: see text] jets. Furthermore, the fraction of events without additional jets above a threshold is measured as a function of the transverse momenta of the leading additional jets and the scalar sum of the transverse momenta of all additional jets. The data are compared and found to be consistent with predictions from several perturbative quantum chromodynamics event generators and a next-to-leading order calculation.
The cross section for [Formula: see text] production in the all-jets final state is measured in pp collisions at a centre-of-mass energy of 8 [Formula: see text] at the LHC with the CMS detector, in data corresponding to an integrated luminosity of 18.4 [Formula: see text]. The inclusive cross section is found to be [Formula: see text] [Formula: see text]. The normalized differential cross sections are measured as a function of the top quark transverse momenta, [Formula: see text], and compared to predictions from quantum chromodynamics. The results are reported at detector, parton, and particle levels. In all cases, the measured top quark [Formula: see text] spectra are significantly softer than theoretical predictions.
New sets of parameters ("tunes") for the underlying-event (UE) modelling of the pythia8, pythia6 and herwig++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE proton-proton ([Formula: see text]) data at [Formula: see text] and to UE proton-antiproton ([Formula: see text]) data from the CDF experiment at lower [Formula: see text], are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13[Formula: see text]. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan ([Formula: see text] lepton-antilepton+jets) observables at 7 and 8[Formula: see text], as well as predictions for MB and UE observables at 13[Formula: see text].
Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton-proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.
This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.
A search for new physics is performed using events with two isolated same-sign leptons, two or more jets, and missing transverse momentum. The results are based on a sample of proton-proton collisions at a center-of-mass energy of 13[Formula: see text] recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 2.3 [Formula: see text]. Multiple search regions are defined by classifying events in terms of missing transverse momentum, the scalar sum of jet transverse momenta, the transverse mass associated with a [Formula: see text] boson candidate, the number of jets, the number of [Formula: see text] quark jets, and the transverse momenta of the leptons in the event. The analysis is sensitive to a wide variety of possible signals beyond the standard model. No excess above the standard model background expectation is observed. Constraints are set on various supersymmetric models, with gluinos and bottom squarks excluded for masses up to 1300 and 680[Formula: see text], respectively, at the 95 % confidence level. Upper limits on the cross sections for the production of two top quark-antiquark pairs (119[Formula: see text]) and two same-sign top quarks (1.7[Formula: see text]) are also obtained. Selection efficiencies and model independent limits are provided to allow further interpretations of the results.
A measurement of the forward-backward asymmetry [Formula: see text] of oppositely charged lepton pairs ([Formula: see text] and [Formula: see text]) produced via [Formula: see text] boson exchange in pp collisions at [Formula: see text] [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 19.7[Formula: see text] collected with the CMS detector at the LHC. The measurement of [Formula: see text] is performed for dilepton masses between 40[Formula: see text] and 2[Formula: see text] and for dilepton rapidity up to 5. The [Formula: see text] measurements as a function of dilepton mass and rapidity are compared with the standard model predictions.
A measurement of the W boson pair production cross section in proton-proton collisions at [Formula: see text] TeV is presented. The data collected with the CMS detector at the LHC correspond to an integrated luminosity of 19.4[Formula: see text]. The [Formula: see text] candidates are selected from events with two charged leptons, electrons or muons, and large missing transverse energy. The measured [Formula: see text] cross section is [Formula: see text], consistent with the standard model prediction. The [Formula: see text] cross sections are also measured in two different fiducial phase space regions. The normalized differential cross section is measured as a function of kinematic variables of the final-state charged leptons and compared with several perturbative QCD predictions. Limits on anomalous gauge couplings associated with dimension-six operators are also given in the framework of an effective field theory. The corresponding 95 % confidence level intervals are [Formula: see text], [Formula: see text], [Formula: see text], in the HISZ basis.
A search for narrow resonances decaying to an electron and a muon is presented. The [Formula: see text] [Formula: see text] mass spectrum is also investigated for non-resonant contributions from the production of quantum black holes (QBHs). The analysis is performed using data corresponding to an integrated luminosity of 19.7[Formula: see text] collected in proton-proton collisions at a centre-of-mass energy of 8[Formula: see text] with the CMS detector at the LHC. With no evidence for physics beyond the standard model in the invariant mass spectrum of selected [Formula: see text] pairs, upper limits are set at 95 [Formula: see text] confidence level on the product of cross section and branching fraction for signals arising in theories with charged lepton flavour violation. In the search for narrow resonances, the resonant production of a [Formula: see text] sneutrino in R-parity violating supersymmetry is considered. The [Formula: see text] sneutrino is excluded for masses below 1.28[Formula: see text] for couplings [Formula: see text], and below 2.30[Formula: see text] for [Formula: see text] and [Formula: see text]. These are the most stringent limits to date from direct searches at high-energy colliders. In addition, the resonance searches are interpreted in terms of a model with heavy partners of the [Formula: see text] boson and the photon. In a framework of TeV-scale quantum gravity based on a renormalization of Newton's constant, the search for non-resonant contributions to the [Formula: see text] [Formula: see text] mass spectrum excludes QBH production below a threshold mass [Formula: see text] of 1.99[Formula: see text]. In models that invoke extra dimensions, the bounds range from 2.36[Formula: see text] for one extra dimension to 3.63[Formula: see text] for six extra dimensions. This is the first search for QBHs decaying into the [Formula: see text] [Formula: see text] final state.
A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons ([Formula: see text]) in proton-proton collisions collected by the CMS experiment at the LHC at [Formula: see text]. The data correspond to an integrated luminosity of 19.7[Formula: see text]. The search considers [Formula: see text] resonances with masses between 1 and 3[Formula: see text], having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and [Formula: see text] events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 % confidence level for the product of the production cross section and branching fraction [Formula: see text] range from 10 to 1.5[Formula: see text] for the mass of X from 1.15 to 2.0[Formula: see text], significantly extending previous searches. For a warped extra dimension theory with a mass scale [Formula: see text] [Formula: see text], the data exclude radion scalar masses between 1.15 and 1.55[Formula: see text].
A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to-largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text].
Measurements of the [Formula: see text][Formula: see text] production cross sections in proton-proton collisions at center-of-mass energies of 7 and 8[Formula: see text] are presented. Candidate events for the leptonic decay mode [Formula: see text], where [Formula: see text] denotes an electron or a muon, are reconstructed and selected from data corresponding to an integrated luminosity of 5.1 (19.6)[Formula: see text] at 7 (8)[Formula: see text] collected with the CMS experiment. The measured cross sections, [Formula: see text] at 7[Formula: see text], and [Formula: see text] at 8[Formula: see text], are in good agreement with the standard model predictions with next-to-leading-order accuracy. The selected data are analyzed to search for anomalous triple gauge couplings involving the [Formula: see text][Formula: see text] final state. In the absence of any deviation from the standard model predictions, limits are set on the relevant parameters. These limits are then combined with the previously published CMS results for [Formula: see text][Formula: see text] in 4[Formula: see text] final states, yielding the most stringent constraints on the anomalous couplings.