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 first search for pair production of dark matter candidates through vector boson fusion in proton-proton collisions at sqrt[s]=8 TeV is performed with the CMS detector. The vector boson fusion topology enhances missing transverse momentum, providing a way to probe supersymmetry, even in the case of a compressed mass spectrum. The data sample corresponds to an integrated luminosity of 18.5 fb^{-1}, recorded by the CMS experiment. The observed dijet mass spectrum is consistent with the standard model expectation. In an effective field theory, dark matter masses are explored as a function of contact interaction strength. The most stringent limit on bottom squark production with mass below 315 GeV is also reported, assuming a 5 GeV mass difference with respect to the lightest neutralino.
A search for the resonant production of high-mass photon pairs is presented. The analysis is based on samples of proton-proton collision data collected by the CMS experiment at center-of-mass energies of 8 and 13 TeV, corresponding to integrated luminosities of 19.7 and 3.3 fb^{-1}, respectively. The interpretation of the search results focuses on spin-0 and spin-2 resonances with masses between 0.5 and 4 TeV and with widths, relative to the mass, between 1.4×10^{-4} and 5.6×10^{-2}. Limits are set on scalar resonances produced through gluon-gluon fusion, and on Randall-Sundrum gravitons. A modest excess of events compatible with a narrow resonance with a mass of about 750 GeV is observed. The local significance of the excess is approximately 3.4 standard deviations. The significance is reduced to 1.6 standard deviations once the effect of searching under multiple signal hypotheses is considered. More data are required to determine the origin of this excess.
Results on two-particle angular correlations for charged particles produced in pp collisions at a center-of-mass energy of 13 TeV are presented. The data were taken with the CMS detector at the LHC and correspond to an integrated luminosity of about 270 nb^{-1}. The correlations are studied over a broad range of pseudorapidity (|η|<2.4) and over the full azimuth (ϕ) as a function of charged particle multiplicity and transverse momentum (p_{T}). In high-multiplicity events, a long-range (|Δη|>2.0), near-side (Δϕ≈0) structure emerges in the two-particle Δη-Δϕ correlation functions. The magnitude of the correlation exhibits a pronounced maximum in the range 1.0
A search for narrow resonances decaying into dijet final states is performed on data from proton-proton collisions at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 18.8 fb^{-1}. The data were collected with the CMS detector using a novel technique called data scouting, in which the information associated with these selected events is much reduced, permitting collection of larger data samples. This technique enables CMS to record events containing jets at a rate of 1 kHz, by collecting the data from the high-level-trigger system. In this way, the sensitivity to low-mass resonances is increased significantly, allowing previously inaccessible couplings of new resonances to quarks and gluons to be probed. The resulting dijet mass distribution yields no evidence of narrow resonances. Upper limits are presented on the resonance cross sections as a function of mass, and compared with a variety of models predicting narrow resonances. The limits are translated into upper limits on the coupling of a leptophobic resonance Z_{B}^{'} to quarks, improving on the results obtained by previous experiments for the mass range from 500 to 800 GeV.
A measurement of the top quark pair production ([Formula: see text]) cross section in proton-proton collisions at the centre-of-mass energy of 8[Formula: see text] is presented using data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 19.6[Formula: see text]. This analysis is performed in the [Formula: see text] decay channels with one isolated, high transverse momentum electron or muon and at least four jets, at least one of which is required to be identified as originating from hadronization of a b quark. The calibration of the jet energy scale and the efficiency of b jet identification are determined from data. The measured [Formula: see text] cross section is [Formula: see text]. This measurement is compared with an analysis of 7[Formula: see text] data, corresponding to an integrated luminosity of 5.0[Formula: see text], to determine the ratio of 8[Formula: see text] to 7[Formula: see text] cross sections, which is found to be [Formula: see text]. The measurements are in agreement with QCD predictions up to next-to-next-to-leading order.
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.
Measurements of the associated production of a Z boson with at least one jet originating from a b quark in proton-proton collisions at
s
= 8
TeV
are presented. Differential cross sections are measured with data collected by the CMS experiment corresponding to an integrated luminosity of 19.8
fb
- 1
. Z bosons are reconstructed through their decays to electrons and muons. Cross sections are measured as a function of observables characterizing the kinematics of the b jet and the Z boson. Ratios of differential cross sections for the associated production with at least one b jet to the associated production with any jet are also presented. The production of a Z boson with at least two b jets is investigated, and differential cross sections are measured for the dijet system. Results are compared to theoretical predictions, testing two different flavour schemes for the choice of initial-state partons.
The WZ production cross section is measured by the CMS experiment at the CERN LHC in proton-proton collision data samples corresponding to integrated luminosities of 4.9[Formula: see text] collected at [Formula: see text], and 19.6[Formula: see text] at [Formula: see text]. The measurements are performed using the fully-leptonic WZ decay modes with electrons and muons in the final state. The measured cross sections for [Formula: see text] are [Formula: see text] [Formula: see text] and [Formula: see text] [Formula: see text]. Differential cross sections with respect to the [Formula: see text] boson [Formula: see text], the leading jet [Formula: see text], and the number of jets are obtained using the [Formula: see text] data. The results are consistent with standard model predictions and constraints on anomalous triple gauge couplings are obtained.
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].
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.
DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement.
The cladded conductor is broadly utilized in engineering fields, such as aerospace, energy, and petrochemical; however, it is vulnerable to thickness loss occurring in the clad layer and nonconductive protection coating due to abrasive and corrosive environments. Such a flaw severely undermines the integrity and safety of the mechanical structures. Therefore, evaluating the thickness loss hidden inside cladded conductors via reliable nondestructive evaluation techniques is imperative. This paper intensively investigates the pulse-modulation eddy current technique (PMEC) for the assessment of thickness loss in a cladded conductor. An analytical model of the ferrite-cored probe is established for analyzing PMEC signals and characteristics of lift-off intersection (LOI) in testing signals. Experiments are conducted for evaluation of the thickness loss in cladded conductors. An inverse scheme based on LOI for estimation of the thickness-loss depth is proposed and further verified. Through simulations and experiments, it is found that the influences of the thickness loss in the clad layer and protective coating on the PMEC signals can be decoupled in virtue of the LOI characteristics. Based on LOI, the hidden thickness loss can be efficiently evaluated without much of a reduction in accuracy by using the PMEC probe for dedicated inspection of the cladded conductor.