Displaying publications 1 - 20 of 111 in total

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  1. Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases
    Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.
    Clin Exp Med, 2024 Mar 16;24(1):53.
    PMID: 38492056 DOI: 10.1007/s10238-024-01311-5
    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
  2. Fulltext Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications"
    Godman B, Wladysiuk M, McTaggart S, Kurdi A, Allocati E, Jakovljevic M, et al.
    Biomed Res Int, 2023;2023:9757348.
    PMID: 37065720 DOI: 10.1155/2023/9757348
    [This corrects the article DOI: 10.1155/2021/9996193.].
  3. Testing a global standard for quantifying species recovery and assessing conservation impact
    Grace MK, Akçakaya HR, Bennett EL, Brooks TM, Heath A, Hedges S, et al.
    Conserv Biol, 2021 12;35(6):1833-1849.
    PMID: 34289517 DOI: 10.1111/cobi.13756
    Recognizing the imperative to evaluate species recovery and conservation impact, in 2012 the International Union for Conservation of Nature (IUCN) called for development of a "Green List of Species" (now the IUCN Green Status of Species). A draft Green Status framework for assessing species' progress toward recovery, published in 2018, proposed 2 separate but interlinked components: a standardized method (i.e., measurement against benchmarks of species' viability, functionality, and preimpact distribution) to determine current species recovery status (herein species recovery score) and application of that method to estimate past and potential future impacts of conservation based on 4 metrics (conservation legacy, conservation dependence, conservation gain, and recovery potential). We tested the framework with 181 species representing diverse taxa, life histories, biomes, and IUCN Red List categories (extinction risk). Based on the observed distribution of species' recovery scores, we propose the following species recovery categories: fully recovered, slightly depleted, moderately depleted, largely depleted, critically depleted, extinct in the wild, and indeterminate. Fifty-nine percent of tested species were considered largely or critically depleted. Although there was a negative relationship between extinction risk and species recovery score, variation was considerable. Some species in lower risk categories were assessed as farther from recovery than those at higher risk. This emphasizes that species recovery is conceptually different from extinction risk and reinforces the utility of the IUCN Green Status of Species to more fully understand species conservation status. Although extinction risk did not predict conservation legacy, conservation dependence, or conservation gain, it was positively correlated with recovery potential. Only 1.7% of tested species were categorized as zero across all 4 of these conservation impact metrics, indicating that conservation has, or will, play a role in improving or maintaining species status for the vast majority of these species. Based on our results, we devised an updated assessment framework that introduces the option of using a dynamic baseline to assess future impacts of conservation over the short term to avoid misleading results which were generated in a small number of cases, and redefines short term as 10 years to better align with conservation planning. These changes are reflected in the IUCN Green Status of Species Standard.
  4. Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging
    Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.
    Cancers (Basel), 2021 Oct 27;13(21).
    PMID: 34771551 DOI: 10.3390/cancers13215388
    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
  5. Altered N-linked glycosylation in endometrial cancer
    Mittal P, Briggs M, Klingler-Hoffmann M, Kaur G, Packer NH, Oehler MK, et al.
    Anal Bioanal Chem, 2021 Apr;413(10):2721-2733.
    PMID: 33222001 DOI: 10.1007/s00216-020-03039-z
    It is well established that cell surface glycans play a vital role in biological processes and their altered form can lead to carcinogenesis. Mass spectrometry-based techniques have become prominent for analysing N-linked glycans, for example using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Additionally, MALDI MS can be used to spatially map N-linked glycans directly from cancer tissue using a technique termed MALDI MS imaging (MALDI MSI). This powerful technique combines mass spectrometry and histology to visualise the spatial distribution of N-linked glycans on a single tissue section. Here, we performed N-glycan MALDI MSI on six endometrial cancer (EC) formalin-fixed paraffin-embedded (FFPE) tissue sections and tissue microarrays (TMA) consisting of eight EC patients with lymph node metastasis (LNM) and twenty without LNM. By doing so, several putative N-linked glycan compositions were detected that could significantly distinguish normal from cancerous endometrium. Furthermore, a complex core-fucosylated N-linked glycan was detected that could discriminate a primary tumour with and without LNM. Structural identification of these putative N-linked glycans was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose glycans in tumour compared to normal regions with AUC ranging from 0.85-0.99, and lower abundance of complex N-linked glycans with AUC ranges from 0.03-0.28. A comparison of N-linked glycans between primary tumours with and without LNM indicated a reduced abundance of a complex core-fucosylated N-glycan (Hex)2(HexNAc)2(Deoxyhexose)1+(Man)3(GlcNAc)2, in primary tumour with associated lymph node metastasis. In summary, N-linked glycan MALDI MSI can be used to differentiate cancerous endometrium from normal, and endometrial cancer with LNM from endometrial cancer without.
  6. Fulltext Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications
    Godman B, Wladysiuk M, McTaggart S, Kurdi A, Allocati E, Jakovljevic M, et al.
    Biomed Res Int, 2021;2021:9996193.
    PMID: 34676266 DOI: 10.1155/2021/9996193
    BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel.

    RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups.

    CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

  7. Author Correction: Area-based conservation in the twenty-first century
    Maxwell SL, Cazalis V, Dudley N, Hoffmann M, Rodrigues ASL, Stolton S, et al.
    Nature, 2020 Dec;588(7837):E14.
    PMID: 33204035 DOI: 10.1038/s41586-020-2952-y
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  8. Uncovering Tumor-Stroma Inter-relationships Using MALDI Mass Spectrometry Imaging
    Boyle ST, Mittal P, Kaur G, Hoffmann P, Samuel MS, Klingler-Hoffmann M
    J Proteome Res, 2020 10 02;19(10):4093-4103.
    PMID: 32870688 DOI: 10.1021/acs.jproteome.0c00511
    Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. We used peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify the proteomic changes occurring within tumors and their stroma in their regular spatial context. Peptides were ranked according to their ability to discriminate between the two groups, using a receiver operating characteristic tool. Peptides were identified by liquid chromatography tandem mass spectrometry, and protein expression was validated by quantitative immunofluorescence using an independent set of tumor samples. We have identified and validated four key proteins upregulated in ROCK-activated mammary tumors relative to those expressing kinase-dead ROCK, namely, collagen I, α-SMA, Rab14, and tubulin-β4. Rab14 and tubulin-β4 are expressed within tumor cells, whereas collagen I is localized within the stroma. α-SMA is predominantly localized within the stroma but is also expressed at higher levels in the epithelia of ROCK-activated tumors. High expression of COL1A, the gene encoding the pro-α 1 chain of collagen, correlates with cancer progression in two human breast cancer genomic data sets, and high expression of COL1A and ACTA2 (the gene encoding α-SMA) are associated with a low survival probability (COLIA, p = 0.00013; ACTA2, p = 0.0076) in estrogen receptor-negative breast cancer patients. To investigate whether ROCK-activated tumor cells cause stromal cancer-associated fibroblasts (CAFs) to upregulate expression of collagen I and α-SMA, we treated CAFs with medium conditioned by primary mammary tumor cells in which ROCK had been activated. This led to abundant production of both proteins in CAFs, clearly highlighting the inter-relationship between tumor cells and CAFs and identifying CAFs as the potential source of high levels of collagen 1 and α-SMA and associated enhancement of tissue stiffness. Our research emphasizes the capacity of MALDI-MSI to quantitatively assess tumor-stroma inter-relationships and to identify potential prognostic factors for cancer progression in human patients, using sophisticated mouse cancer models.
  9. Area-based conservation in the twenty-first century
    Maxwell SL, Cazalis V, Dudley N, Hoffmann M, Rodrigues ASL, Stolton S, et al.
    Nature, 2020 10;586(7828):217-227.
    PMID: 33028996 DOI: 10.1038/s41586-020-2773-z
    Humanity will soon define a new era for nature-one that seeks to transform decades of underwhelming responses to the global biodiversity crisis. Area-based conservation efforts, which include both protected areas and other effective area-based conservation measures, are likely to extend and diversify. However, persistent shortfalls in ecological representation and management effectiveness diminish the potential role of area-based conservation in stemming biodiversity loss. Here we show how the expansion of protected areas by national governments since 2010 has had limited success in increasing the coverage across different elements of biodiversity (ecoregions, 12,056 threatened species, 'Key Biodiversity Areas' and wilderness areas) and ecosystem services (productive fisheries, and carbon services on land and sea). To be more successful after 2020, area-based conservation must contribute more effectively to meeting global biodiversity goals-ranging from preventing extinctions to retaining the most-intact ecosystems-and must better collaborate with the many Indigenous peoples, community groups and private initiatives that are central to the successful conservation of biodiversity. The long-term success of area-based conservation requires parties to the Convention on Biological Diversity to secure adequate financing, plan for climate change and make biodiversity conservation a far stronger part of land, water and sea management policies.
  10. Fulltext Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis
    Ekker MS, Jacob MA, van Dongen MME, Aarnio K, Annamalai AK, Arauz A, et al.
    BMJ Open, 2019 Nov 14;9(11):e031144.
    PMID: 31727655 DOI: 10.1136/bmjopen-2019-031144
    INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients.

    METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.

    ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

  11. Translating N-Glycan Analytical Applications into Clinical Strategies for Ovarian Cancer
    Briggs MT, Condina MR, Klingler-Hoffmann M, Arentz G, Everest-Dass AV, Kaur G, et al.
    Proteomics Clin Appl, 2019 05;13(3):e1800099.
    PMID: 30367710 DOI: 10.1002/prca.201800099
    Protein glycosylation, particularly N-linked glycosylation, is a complex posttranslational modification (PTM), which plays an important role in protein folding and conformation, regulating protein stability and activity, cell-cell interaction, and cell signaling pathways. This review focuses on analytical techniques, primarily MS-based techniques, to qualitatively and quantitatively assess N-glycosylation while successfully characterizing compositional, structural, and linkage features with high specificity and sensitivity. The analytical techniques explored in this review include LC-ESI-MS/MS and MALDI time-of-flight MS (MALDI-TOF-MS), which have been used to analyze clinical samples, such as serum, plasma, ascites, and tissue. Targeting the aberrant N-glycosylation patterns observed in MALDI-MS imaging (MSI) offers a platform to visualize N-glycans in tissue-specific regions. The studies on the intra-patient (i.e., a comparison of tissue-specific regions from the same patient) and inter-patient (i.e., a comparison of tissue-specific regions between different patients) variation of early- and late-stage ovarian cancer (OC) patients identify specific N-glycan differences that improve understanding of the tumor microenvironment and potentially improve therapeutic strategies for the clinic.
  12. Search for the Higgs Boson Decaying to Two Muons in Proton-Proton Collisions at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2019 Jan 18;122(2):021801.
    PMID: 30720313 DOI: 10.1103/PhysRevLett.122.021801
    A search for the Higgs boson decaying to two oppositely charged muons is presented using data recorded by the CMS experiment at the CERN LHC in 2016 at a center-of-mass energy sqrt[s]=13  TeV, corresponding to an integrated luminosity of 35.9  fb^{-1}. Data are found to be compatible with the predicted background. For a Higgs boson with a mass of 125.09 GeV, the 95% confidence level observed (background-only expected) upper limit on the production cross section times the branching fraction to a pair of muons is found to be 3.0 (2.5) times the standard model expectation. In combination with data recorded at center-of-mass energies sqrt[s]=7 and 8 TeV, the background-only expected upper limit improves to 2.2 times the standard model value with a standard model expected significance of 1.0 standard deviation. The corresponding observed upper limit is 2.9 with an observed significance of 0.9 standard deviation. This corresponds to an observed upper limit on the standard model Higgs boson branching fraction to muons of 6.4×10^{-4} and to an observed signal strength of 1.0±1.0(stat)±0.1(syst).
  13. Fulltext Measurement of exclusive Υ photoproduction from protons in p Pb collisions at s NN = 5.02 TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2019;79(3):277.
    PMID: 31007586 DOI: 10.1140/epjc/s10052-019-6774-8
    The exclusive photoproduction of Υ ( nS ) meson states from protons, γ p → Υ ( nS ) p (with n = 1 , 2 , 3 ), is studied in ultraperipheral p Pb collisions at a centre-of-mass energy per nucleon pair of s NN = 5.02 TeV . The measurement is performed using the Υ ( nS ) → μ + μ - decay mode, with data collected by the CMS experiment corresponding to an integrated luminosity of 32.6 nb - 1 . Differential cross sections as functions of the Υ ( nS ) transverse momentum squared p T 2 , and rapidity y, are presented. The Υ ( 1 S ) photoproduction cross section is extracted in the rapidity range | y | < 2.2 , which corresponds to photon-proton centre-of-mass energies in the range 91 < W γ p < 826 GeV . The data are compared to theoretical predictions based on perturbative quantum chromodynamics and to previous measurements.
  14. Observation of Medium-Induced Modifications of Jet Fragmentation in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV Using Isolated Photon-Tagged Jets
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 Dec 14;121(24):242301.
    PMID: 30608764 DOI: 10.1103/PhysRevLett.121.242301
    Measurements of fragmentation functions for jets associated with an isolated photon are presented for the first time in pp and Pb-Pb collisions. The analysis uses data collected with the CMS detector at the CERN LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Fragmentation functions are obtained for jets with p_{T}^{jet}>30  GeV/c in events containing an isolated photon with p_{T}^{γ}>60  GeV/c, using charged tracks with transverse momentum p_{T}^{trk}>1  GeV/c in a cone around the jet axis. The association with an isolated photon constrains the initial p_{T} and azimuthal angle of the parton whose shower produced the jet. For central Pb-Pb collisions, modifications of the jet fragmentation functions are observed when compared to those measured in pp collisions, while no significant differences are found in the 50% most peripheral collisions. Jets in central Pb-Pb events show an excess (depletion) of low (high) p_{T} particles, with a transition around 3  GeV/c. This measurement shows for the first time the in-medium shower modifications of partons (quark dominated) with well-defined initial kinematics. It constitutes a new well-controlled reference for testing theoretical models of the parton passage through the quark-gluon plasma.
  15. Elliptic Flow of Charm and Strange Hadrons in High-Multiplicity p+Pb Collisions at sqrt[s_{NN}]=8.16  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 Aug 24;121(8):082301.
    PMID: 30192601 DOI: 10.1103/PhysRevLett.121.082301
    The elliptic azimuthal anisotropy coefficient (v_{2}) is measured for charm (D^{0}) and strange (K_{S}^{0}, Λ, Ξ^{-}, and Ω^{-}) hadrons, using a data sample of p+Pb collisions collected by the CMS experiment, at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=8.16  TeV. A significant positive v_{2} signal from long-range azimuthal correlations is observed for all particle species in high-multiplicity p+Pb collisions. The measurement represents the first observation of possible long-range collectivity for open heavy flavor hadrons in small systems. The results suggest that charm quarks have a smaller v_{2} than the lighter quarks, probably reflecting a weaker collective behavior. This effect is not seen in the larger PbPb collision system at sqrt[s_{NN}]=5.02  TeV, also presented.
  16. Search for Physics Beyond the Standard Model in Events with High-Momentum Higgs Bosons and Missing Transverse Momentum in Proton-Proton Collisions at 13 TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 Jun 15;120(24):241801.
    PMID: 29956995 DOI: 10.1103/PhysRevLett.120.241801
    A search for physics beyond the standard model in events with one or more high-momentum Higgs bosons, H, decaying to pairs of b quarks in association with missing transverse momentum is presented. The data, corresponding to an integrated luminosity of 35.9  fb^{-1}, were collected with the CMS detector at the LHC in proton-proton collisions at the center-of-mass energy sqrt[s]=13  TeV. The analysis utilizes a new b quark tagging technique based on jet substructure to identify jets from H→bb[over ¯]. Events are categorized by the multiplicity of H-tagged jets, jet mass, and the missing transverse momentum. No significant deviation from standard model expectations is observed. In the context of supersymmetry (SUSY), limits on the cross sections of pair-produced gluinos are set, assuming that gluinos decay to quark pairs, H (or Z), and the lightest SUSY particle, LSP, through an intermediate next-to-lightest SUSY particle, NLSP. With large mass splitting between the NLSP and LSP, and 100% NLSP branching fraction to H, the lower limit on the gluino mass is found to be 2010 GeV.
  17. Search for Heavy Neutral Leptons in Events with Three Charged Leptons in Proton-Proton Collisions at sqrt[s]=13  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 Jun 01;120(22):221801.
    PMID: 29906166 DOI: 10.1103/PhysRevLett.120.221801
    A search for a heavy neutral lepton N of Majorana nature decaying into a W boson and a charged lepton is performed using the CMS detector at the LHC. The targeted signature consists of three prompt charged leptons in any flavor combination of electrons and muons. The data were collected in proton-proton collisions at a center-of-mass energy of 13 TeV, with an integrated luminosity of 35.9  fb^{-1}. The search is performed in the N mass range between 1 GeV and 1.2 TeV. The data are found to be consistent with the expected standard model background. Upper limits are set on the values of |V_{eN}|^{2} and |V_{μN}|^{2}, where V_{ℓN} is the matrix element describing the mixing of N with the standard model neutrino of flavor ℓ. These are the first direct limits for N masses above 500 GeV and the first limits obtained at a hadron collider for N masses below 40 GeV.
  18. Search for the X(5568) State Decaying into B_{s}^{0}π^{±} in Proton-Proton Collisions at sqrt[s]=8  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 May 18;120(20):202005.
    PMID: 29864318 DOI: 10.1103/PhysRevLett.120.202005
    A search for resonancelike structures in the B_{s}^{0}π^{±} invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at sqrt[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/ψϕ, with J/ψ→μ^{+}μ^{-} and ϕ→K^{+}K^{-}. The B_{s}^{0}π^{±} invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B_{s}^{0} and π^{±} 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}π^{±}. 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}π^{±}.
  19. Search for Narrow Resonances in the b-Tagged Dijet Mass Spectrum in Proton-Proton Collisions at sqrt[s]=8  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 May 18;120(20):201801.
    PMID: 29864370 DOI: 10.1103/PhysRevLett.120.201801
    A search for narrow resonances decaying to bottom quark-antiquark pairs is presented, using a data sample of proton-proton collisions at sqrt[s]=8  TeV corresponding to an integrated luminosity of 19.7  fb^{-1}. The search is extended to masses lower than those reached in typical searches for resonances decaying into jet pairs at the LHC, by taking advantage of triggers that identify jets originating from bottom quarks. No significant excess of events is observed above the background predictions. Limits are set on the product of cross section and branching fraction to bottom quarks for spin 0, 1, and 2 resonances in the mass range of 325-1200 GeV. These results improve on the limits for resonances decaying into jet pairs in the 325-500 GeV mass range.
  20. Measurement of Prompt D^{0} Meson Azimuthal Anisotropy in Pb-Pb Collisions at sqrt[s_{NN}]=5.02  TeV
    Sirunyan AM, Tumasyan A, Adam W, Ambrogi F, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2018 May 18;120(20):202301.
    PMID: 29864330 DOI: 10.1103/PhysRevLett.120.202301
    The prompt D^{0} meson azimuthal anisotropy coefficients, v_{2} and v_{3}, are measured at midrapidity (|y|<1.0) in Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02  TeV per nucleon pair with data collected by the CMS experiment. The measurement is performed in the transverse momentum (p_{T}) range of 1 to 40  GeV/c, for central and midcentral collisions. The v_{2} coefficient is found to be positive throughout the p_{T} range studied. The first measurement of the prompt D^{0} meson v_{3} coefficient is performed, and values up to 0.07 are observed for p_{T} around 4  GeV/c. Compared to measurements of charged particles, a similar p_{T} dependence, but smaller magnitude for p_{T}<6  GeV/c, is found for prompt D^{0} meson v_{2} and v_{3} coefficients. The results are consistent with the presence of collective motion of charm quarks at low p_{T} and a path length dependence of charm quark energy loss at high p_{T}, thereby providing new constraints on the theoretical description of the interactions between charm quarks and the quark-gluon plasma.
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