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| 13. |
- Chen, DS, et al.
(author)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Journal article (peer-reviewed)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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| 16. |
- He, YQ, et al.
(author)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Journal article (peer-reviewed)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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| 17. |
- Hu, XH, et al.
(author)
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Neogenin suppresses tumor progression and metastasis via inhibiting Merlin/YAP signaling
- 2023
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In: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 9:1, s. 47-
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Journal article (peer-reviewed)abstract
- From in situ growth to invasive dissemination is the most lethal attribute of various tumor types. This transition is majorly mediated by the dynamic interplay between two cancer hallmarks, EMT and cell cycle. In this study, we applied nonlinear association analysis in 33 cancer types and found that most signaling receptors simultaneously associating with EMT and cell cycle are potential tumor suppressors. Here we find that a top co-associated receptor, Neogenin (NEO1), inhibits colorectal cancer (CRC) and Glioma in situ growth and metastasis by forming a complex with Merlin (NF2), and subsequent simultaneous promoting the phosphorylation of YAP. Furthermore, Neogenin protein level is associated with good prognosis and correlates with Merlin status in CRC and Glioma. Collectively, our results define Neogenin as a tumor suppressor in CRC and Glioma that acts by restricting oncogenic signaling by the Merlin-YAP pathway, and suggest Neogenin as a candidate therapeutic agent for CRC and Glioma.
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| 24. |
- Ren, WC, et al.
(author)
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Genetic landscape of hepatitis B virus-associated diffuse large B-cell lymphoma
- 2018
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 131:24, s. 2670-2681
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Journal article (peer-reviewed)abstract
- Hepatitis B virus (HBV) infection is endemic in some parts of Asia, Africa, and South America and remains to be a significant public health problem in these areas. It is known as a leading risk factor for the development of hepatocellular carcinoma, but epidemiological studies have also shown that the infection may increase the incidence of several types of B-cell lymphoma. Here, by characterizing altogether 275 Chinese diffuse large B-cell lymphoma (DLBCL) patients, we showed that patients with concomitant HBV infection (surface antigen positive [HBsAg+]) are characterized by a younger age, a more advanced disease stage at diagnosis, and reduced overall survival. Furthermore, by whole-genome/exome sequencing of 96 tumors and the respective peripheral blood samples and targeted sequencing of 179 tumors from these patients, we observed an enhanced rate of mutagenesis and a distinct set of mutation targets in HBsAg+ DLBCL genomes, which could be partially explained by the activities of APOBEC and activation-induced cytidine deaminase. By transcriptome analysis, we further showed that the HBV-associated gene expression signature is contributed by the enrichment of genes regulated by BCL6, FOXO1, and ZFP36L1. Finally, by analysis of immunoglobulin heavy chain gene sequences, we showed that an antigen-independent mechanism, rather than a chronic antigenic simulation model, is favored in HBV-related lymphomagenesis. Taken together, we present the first comprehensive genomic and transcriptomic study that suggests a link between HBV infection and B-cell malignancy. The genetic alterations identified in this study may also provide opportunities for development of novel therapeutic strategies.
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| 27. |
- Tan, SY, et al.
(author)
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Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity
- 2021
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:9
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Journal article (peer-reviewed)abstract
- The maturation and functional competence of natural killer (NK) cells is a tightly controlled process that relies on transcription factors (TFs). Here, we identify transcriptional repressor zinc fingers and homeoboxes 2 (Zhx2) as a novel regulator that restricts NK cell maturation and function. Mice with Zhx2 conditional deletion in NK cells (Zhx2Δ/Δ) showed accumulation of matured NK cells. Loss of Zhx2 enhanced NK cell survival and NK cell response to IL-15. Transcriptomic analysis revealed Zeb2, a key TF in NK cell terminal maturation, as a direct downstream target of Zhx2. Therapeutically, transfer of Zhx2-deficient NK cells resulted in inhibition of tumor growth and metastasis in different murine models. Our findings collectively unmask a previously unrecognized role of Zhx2 as a novel negative regulator in NK cell maturation and highlight its therapeutic potential as a promising strategy to enhance NK cell–mediated tumor surveillance.
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| 29. |
- Adcox, K, et al.
(author)
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Centrality dependence of the high (PT) charged hadron suppression in Au+Au collisions at root s(NN)=130 GeV
- 2003
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 561:1-2, s. 82-92
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Journal article (peer-reviewed)abstract
- PHENIX has measured the centrality dependence of charged hadron p(T) spectra from Au +An collisions at root(s)NN = 130 GeV The truncated mean p(T) decreases with centrality for p(T) > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p(T) hadrdn production. For central collisions the yield at high p(T) is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p + p, data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e., for collisions with less than similar to140 participating nucleons. The observed p(T) and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions. (C) 2003 Published by Elsevier Science B.V.
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| 30. |
- Adcox, K, et al.
(author)
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Event-by-event fluctuations in mean p(T) and mean E(T) in root s(NN)=130 GeVAu+Au collisions
- 2002
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:2
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Journal article (peer-reviewed)abstract
- Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at roots(NN)=130 GeV at the Relativistic Heavy-Ion Collider. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of nonstatistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant nonrandom fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p(T) or e(T) spectra, we exclude a region of fluctuations in roots(NN)=130 GeV Au+Au collisions.
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| 31. |
- Adcox, K, et al.
(author)
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Flow Measurements via Two-Particle Azimuthal Correlations in Au+Au Collisions at sqrt[sNN]=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 89
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Journal article (peer-reviewed)abstract
- Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider (sqrt[sNN]=130 GeV). The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values (v2) show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone ε, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low pT. A breakdown of this ε scaling is observed for charged hadrons with pT >1.0 GeV/c.
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| 32. |
- Adcox, K, et al.
(author)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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In: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Research review (peer-reviewed)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 33. |
- Adcox, K, et al.
(author)
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Measurement of Lambda and (Lambda)over-bar particles in Au plus Au collisions at root s(NN)=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 89:9
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Journal article (peer-reviewed)abstract
- We present results on the measurement of Lambda and (&ULambda;) over bar production in Au+Au collisions at roots(NN)=130 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider. The transverse momentum spectra were measured for minimum bias and for the 5% most central events. The (&ULambda;) over bar/Lambda ratios are constant as a function of p(T) and the number of participants. The measured net Lambda density is significantly larger than predicted by models based on hadronic strings (e.g., HIJING) but in approximate agreement with models which include the gluon-junction mechanism.
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| 34. |
- Adcox, K, et al.
(author)
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Measurement of single electrons and implications for charm production in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 88:19
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Journal article (peer-reviewed)abstract
- Transverse momentum spectra of electrons from Au+Au collisions at roots(NN) = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025 +/- 0.004(stat) +/- 0.010( syst) in central collisions, and the corresponding charm cross section is 380 +/- 60(stat) +/- 200(syst ) mub per binary nucleon-nucleon collision.
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| 35. |
- Adcox, K, et al.
(author)
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Net charge fluctuations in Au+Au interactions root s(NN)=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 89
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Journal article (peer-reviewed)abstract
- Data from Au+ Au interactions at s(NN)=130 GeV, obtained with the PHENIX detector at the Relativistic Heavy-Ion Collider, are used to investigate local net charge fluctuations among particles produced near midrapidity. According to recent suggestions, such fluctuations may carry information from the quark-gluon plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.
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| 36. |
- Adcox, K, et al.
(author)
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PHENIX detector overview
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 37. |
- Adcox, K, et al.
(author)
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Suppression of hadrons with large transverse momentum in central Au+Au collisions at root s(NN)=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 88:2
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Journal article (peer-reviewed)abstract
- Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 Gev/c < P-T < 5 GeV/c have been measured by the PHENIX experiment at RHIC in Au + Au collisions at rootS(NN) = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p + p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p + p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.
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| 38. |
- Adcox, K, et al.
(author)
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Transverse-mass dependence of two-pion correlations in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
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In: Physical Review Letters. - 1079-7114. ; 88:19
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Journal article (peer-reviewed)abstract
- Two-pion correlations in roots(NN) = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to results from heavy-ion collisions at roots(NN) = 4.1 , 4.9, and 17.3 GeV, whereas the longitudinal radius increases monotonically with beam energy. The ratio of the outwards to sidewards transverse radii (R-out/R-side) is consistent with unity and independent of k(T) .
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| 39. |
- Adler, SS, et al.
(author)
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Double helicity asymmetry in inclusive midrapidity pi(0) production for polarized p+p collisions at root s=200 GeV
- 2004
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In: Physical Review Letters. - 1079-7114. ; 93:20: 202002
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Journal article (peer-reviewed)abstract
- We present a measurement of the double longitudinal spin asymmetry in inclusive pi(0) production in polarized proton-proton collisions at roots=200 GeV. The data were taken at the Relativistic Heavy Ion Collider with average beam polarizations of 0.27. The measurements are the first in a program to study the longitudinal spin structure of the proton, using strongly interacting probes, at collider energies. The asymmetry is presented for transverse momenta 1-5 GeV/c at midrapidity, where next-to-leading-order perturbative quantum chromodynamic (NLO pQCD) calculations well describe the unpolarized cross section. The observed asymmetry is small and is compared to a NLO pQCD calculation with a range of polarized gluon distributions.
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