Determining PTEN Functional Status by Network Component Deduced Transcription Factor Activities

PTEN-controlled PI3K-AKT-mTOR pathway represents one of the most deregulated signaling pathways in human cancers. With many small molecule inhibitors that target PI3K-AKT-mTOR pathway being exploited clinically, sensitive and reliable ways of stratifying patients according to their PTEN functional status and determining treatment outcomes are urgently needed. Heterogeneous loss of PTEN is commonly associated with human cancers and yet PTEN can also be regulated on epigenetic, transcriptional or post-translational levels, which makes the use of simple protein or gene expression-based analyses in determining PTEN status less accurate. In this study, we used network component analysis to identify 20 transcription factors (TFs) whose activities deduced from their target gene expressions were immediately altered upon the re-expression of PTEN in a PTEN-inducible system. Interestingly, PTEN controls the activities (TFA) rather than the expression levels of majority of these TFs and these PTEN-controlled TFAs are substantially altered in prostate cancer mouse models. Importantly, the activities of these TFs can be used to predict PTEN status in human prostate, breast and brain tumor samples with enhanced reliability when compared to straightforward IHC-based or expression-based analysis. Furthermore, our analysis indicates that unique sets of PTEN-controlled TFAs significantly contribute to specific tumor types. Together, our findings reveal that TFAs may be used as “signatures” for predicting PTEN functional status and elucidate the transcriptional architectures underlying human cancers caused by PTEN loss

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Search for the X(5568) State Decaying into B-s(0)pi(+/-) in Proton-Proton Collisions at root s=8 TeV

A search for resonancelike structures in the B-s(0)pi(+/-) invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at root s = 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The B-s(0) mesons are reconstructed in the decay chain B-s(0) -> J/Psi phi, with J/Psi -> mu(+) mu(-) and phi -> K+K-. The B-s(0)pi(+/-) invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B-s(0) and pi(+/-) candidates. Upper limits are set on the relative production rates of the X(5568) and B-s(0) states times the branching fraction of the decay X(5568)(+/-) -> B-s(0)pi(+/-). In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into B-s(0)pi(+/-).Peer reviewe

Measurement of inclusive very forward jet cross sections in proton-lead collisions at \sqrt{sNN} = 5:02 TeV

Measurements of differential cross sections for inclusive very forward jet production in proton-lead collisions as a function of jet energy are presented. The data were collected with the CMS experiment at the LHC in the laboratory pseudorapidity range −6.6 < η < −5.2. Asymmetric beam energies of 4 TeV for protons and 1.58 TeV per nucleon for Pb nuclei were used, corresponding to a center-of-mass energy per nucleon pair of \sqrt{sNN} = 5:02 TeV. Collisions with either the proton (p+Pb) or the ion (Pb+p) traveling towards the negative η hemisphere are studied. The jet cross sections are unfolded to stable-particle level cross sections with p_{T} ≳ 3 GeV, and compared to predictions from various Monte Carlo event generators. In addition, the cross section ratio of p+Pb and Pb+p data is presented. The results are discussed in terms of the saturation of gluon densities at low fractional parton momenta. None of the models under consideration describes all the data over the full jet-energy range and for all beam configurations. Discrepancies between the differential cross sections in data and model predictions of more than two orders of magnitude are observed

Measurement of nuclear modification factors of ϒ(1S), ϒ(2S), and ϒ(3S) mesons in PbPb collisions at √sNN = 5.02 TeV

The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead–lead (PbPb) and proton–proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date

Search for low-mass dilepton resonances in Higgs boson decays to four-lepton final states in proton–proton collisions at √s=13TeV

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: For CMS Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” (https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2).]Copyright © CERN for the benefit of the CMS collaboration 2022. A search for low-mass dilepton resonances in Higgs boson decays is conducted in the four-lepton final state. The decay is assumed to proceed via a pair of beyond the standard model particles, or one such particle and a Z boson. The search uses proton–proton collision data collected with the CMS detector at the CERN LHC, corresponding to an integrated luminosity of 137fb−1, at a center-of-mass energy s√=13TeV. No significant deviation from the standard model expectation is observed. Upper limits at 95% confidence level are set on model-independent Higgs boson decay branching fractions. Additionally, limits on dark photon and axion-like particle production, based on two specific models, are reported.SCOAP3

Measurement of prompt ψ(2S) production cross sections in proton–lead and proton–proton collisions at √sNN = 5.02 TeV

Measurements of prompt ψ(2S) meson production cross sections in proton–lead (pPb) and proton–proton (pp) collisions at a nucleon–nucleon center-of-mass energy of √sNN = 5.02 TeV are reported. The results are based on pPb and pp data collected by the CMS experiment at the LHC, corresponding to integrated luminosities of 34.6 nb−1 and 28.0 pb−1, respectively. The nuclear modification factor RpPb is measured for prompt ψ(2S) in the transverse momentum range 4 < pT < 30 GeV/c and the center-of-mass rapidity range −2.4 < yCM < 1.93. The results on ψ(2S) RpPb are compared to the corresponding modification factor for prompt J/ψ mesons. The results point to different nuclear effects at play in the production of the excited charmonium state compared to the ground state, in the region of backward rapidity and for pT < 10 GeV/c