Co-activation of NF-κB and MYC renders cancer cells addicted to IL6 for survival and phenotypic stability

NF-κB and MYC are found co-deregulated in human B and plasma-cell cancers. In physiology, NF-κB is necessary for terminal B-to-plasma cell differentiation, whereas MYC repression is required. It is thus unclear if NF-κB/MYC co-deregulation is developmentally compatible in carcinogenesis and/or impacts cancer cell differentiation state, possibly uncovering unique sensitivities. Using a mouse system to trace cell lineage and oncogene activation we found that NF-κB/MYC co-deregulation originated cancers with a plasmablast-like phenotype, alike human plasmablastic-lymphoma and was linked to t(8;14)[MYC-IGH] multiple myeloma. Notably, in contrast to NF-κB or MYC activation alone, co-deregulation rendered cells addicted to IL6 for survival and phenotypic stability. We propose that conflicting oncogene-driven differentiation pressures can be accommodated at a cost in poorly-differentiated cancers. SIGNIFICANCE: Our studies improve the understanding of cancer pathogenesis by demonstrating that co-deregulation of NF-κB and MYC synergize in forming a cancer with a poorly-differentiated state. The cancers in the mouse system share features with human Plasmablastic lymphoma that has a dismal prognosis and no standard of care, and with t(8;14)[MYC-IGH] Multiple myeloma, which is in overall resistant to standard therapy. Notably, we found that NF-κB and MYC co-deregulation uniquely render cells sensitive to IL6 deprivation, providing a road-map for patient selection. Because of the similarity of the cancers arising in the compound mutant mouse model with that of human Plasmablastic lymphoma and t(8;14)[MYC-IGH] Multiple myeloma, this model could serve in preclinical testing to investigate novel therapies for these hard-to-treat diseases

Advances in light transverse momenta and optical lateral forces

Harnessing linear and angular momenta of light is one of the cornerstones in modern optics and has found tremendous applications in optical circuits, particle manipulation, metrology, quantum information processing, etc. Emerging theoretical protocols and experimental explorations have created a surge of interest in light lateral momenta and forces, which are perpendicular to the light wave propagation direction. However, there is yet a lack of a comprehensive and holistic overview of transverse momenta (both linear and angular) as well as of optical lateral forces (OLFs). In this article, we first review the most recent transverse momenta including the transverse spin angular momentum, optical skyrmions, as well as lateral momenta from directional side scattering, spin-orbit interaction, and surface plasmon polaritons. Since optical forces result from the momentum exchange between light and matter, the transverse momentum consequently gives rise to intriguing OLFs, which is the second topic of this article. Additional non-trivial lateral forces that combine optics with other effects from thermodynamics, electricity, and microfluidics, are also discussed. It should be emphasized that these momenta and forces ubiquitously exist in a broad range of optical phenomena and have often been neglected due to their unpredicted underlying physics and shortage of experimental means, especially prior to the last decade. © 2023 Optica Publishing Group.Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for the associated production of the Higgs boson with a top-quark pair

A search for the standard model Higgs boson produced in association with a top-quark pair t t ¯ H (tt¯H) is presented, using data samples corresponding to integrated luminosities of up to 5.1 fb −1 and 19.7 fb −1 collected in pp collisions at center-of-mass energies of 7 TeV and 8 TeV respectively. The search is based on the following signatures of the Higgs boson decay: H → hadrons, H → photons, and H → leptons. The results are characterized by an observed t t ¯ H tt¯H signal strength relative to the standard model cross section, μ = σ/σ SM ,under the assumption that the Higgs boson decays as expected in the standard model. The best fit value is μ = 2.8 ± 1.0 for a Higgs boson mass of 125.6 GeV

Measurement of prompt Jψ\psi pair production in pp collisions at \sqrt s = 7 Tev

Production of prompt J/ ψ meson pairs in proton-proton collisions at s s√ = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb −1 . The two J/ ψ mesons are fully reconstructed via their decays into μ + μ − pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ ψ pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ ψ transverse momentum ( p T J/ ψ ) and rapidity (| y J/ ψ |): | y J/ ψ | 6.5 GeV/ c ; 1.2 4.5 GeV/ c . The total cross section, assuming unpolarized prompt J/ ψ pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ ψ polarization imply modifications to the cross section ranging from −31% to +27%

Measurements of the t(t)Overbar charge asymmetry using the dilepton decay channel in pp collisions at root s=7 TeV

The tt¯ charge asymmetry in proton-proton collisions at s√ = 7 TeV is measured using the dilepton decay channel (ee, e μ , or μμ ). The data correspond to a total integrated luminosity of 5.0 fb −1 , collected by the CMS experiment at the LHC. The tt and lepton charge asymmetries, defined as the differences in absolute values of the rapidities between the reconstructed top quarks and antiquarks and of the pseudorapidities between the positive and negative leptons, respectively, are measured to be A C = −0 . 010 ± 0 . 017 (stat . ) ± 0 . 008 (syst . ) and AlepC = 0 . 009 ± 0 . 010 (stat . ) ± 0 . 006 (syst . ). The lepton charge asymmetry is also measured as a function of the invariant mass, rapidity, and transverse momentum of the tt¯ system. All measurements are consistent with the expectations of the standard model

Combined pre-supernova alert system with KamLAND and Super-Kamiokande

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance

Charged-particle nuclear modification factors in PbPb and pPb collisions at √=sNN=5.02 TeV

The spectra of charged particles produced within the pseudorapidity window |η| < 1 at √ sNN = 5.02 TeV are measured using 404 µb −1 of PbPb and 27.4 pb−1 of pp data collected by the CMS detector at the LHC in 2015. The spectra are presented over the transverse momentum ranges spanning 0.5 < pT < 400 GeV in pp and 0.7 < pT < 400 GeV in PbPb collisions. The corresponding nuclear modification factor, RAA, is measured in bins of collision centrality. The RAA in the 5% most central collisions shows a maximal suppression by a factor of 7–8 in the pT region of 6–9 GeV. This dip is followed by an increase, which continues up to the highest pT measured, and approaches unity in the vicinity of pT = 200 GeV. The RAA is compared to theoretical predictions and earlier experimental results at lower collision energies. The newly measured pp spectrum is combined with the pPb spectrum previously published by the CMS collaboration to construct the pPb nuclear modification factor, RpA, up to 120 GeV. For pT > 20 GeV, RpA exhibits weak momentum dependence and shows a moderate enhancement above unity