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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.
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Data from heavy ion collisions suggest that the evolution of a parton shower is modified by interactions with the color charges in the dense partonic medium created in these collisions, but it is not known where in the shower evolution the modifications occur. The momentum ratio of the two leading partons, resolved as subjets, provides information about the parton shower evolution. This substructure observable, known as the splitting function, reflects the process of a parton splitting into two other partons and has been measured for jets with transverse momentum between 140 and 500 GeV, in pp and PbPb collisions at a center-of-mass energy of 5.02 TeV per nucleon pair. In central PbPb collisions, the splitting function indicates a more unbalanced momentum ratio, compared to peripheral PbPb and pp collisions.. The measurements are compared to various predictions from event generators and analytical calculations.
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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 Hâbb[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.
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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}âJ/ψÏ, with J/ψâµ^{+}µ^{-} and ÏâK^{+}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)^{±}âB_{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^{±}.
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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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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.
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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_{âN} is the matrix element describing the mixing of N with the standard model neutrino of flavor â. 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.
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An inclusive search for the standard model Higgs boson (H) produced with large transverse momentum (p_{T}) and decaying to a bottom quark-antiquark pair (bb[over ¯]) is performed using a data set of pp collisions at sqrt[s]=13 TeV collected with the CMS experiment at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1}. A highly Lorentz-boosted Higgs boson decaying to bb[over ¯] is reconstructed as a single, large radius jet, and it is identified using jet substructure and dedicated b tagging techniques. The method is validated with Zâbb[over ¯] decays. The Zâbb[over ¯] process is observed for the first time in the single-jet topology with a local significance of 5.1 standard deviations (5.8 expected). For a Higgs boson mass of 125 GeV, an excess of events above the expected background is observed (expected) with a local significance of 1.5 (0.7) standard deviations. The measured cross section times branching fraction for production via gluon fusion of Hâbb[over ¯] with reconstructed p_{T}>450 GeV and in the pseudorapidity range -2.5<η<2.5 is 74±48(stat)_{-10}^{+17}(syst) fb, which is consistent within uncertainties with the standard model prediction.
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The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1} collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. The observed significance of the signal is 5.5 standard deviations, where a significance of 5.7 standard deviations is expected based on the standard model. The ratio of measured event yields to that expected from the standard model at leading order is 0.90±0.22. A cross section measurement in a fiducial region is reported. Bounds are given on the structure of quartic vector boson interactions in the framework of dimension-8 effective field theory operators and on the production of doubly charged Higgs bosons.
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The azimuthal anisotropy Fourier coefficients (v_{n}) in 8.16 TeV p+Pb data are extracted via long-range two-particle correlations as a function of the event multiplicity and compared to corresponding results in pp and PbPb collisions. Using a four-particle cumulant technique, v_{n} correlations are measured for the first time in pp and p+Pb collisions. The v_{2} and v_{4} coefficients are found to be positively correlated in all collision systems. For high-multiplicity p+Pb collisions, an anticorrelation of v_{2} and v_{3} is observed, with a similar correlation strength as in PbPb data at the same multiplicity. The new correlation results strengthen the case for a common origin of the collectivity seen in p+Pb and PbPb collisions in the measured multiplicity range.
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Intrinsically disordered regions within proteins are critical elements in many biomolecular interactions and signaling pathways. Antibacterial toxins of the colicin family, which could provide new antibiotic functions against resistant bacteria, contain disordered N-terminal translocation domains (T-domains) that are essential for receptor binding and the penetration of the Escherichia coli outer membrane. Here we investigate the conformational behavior of the T-domain of colicin N (ColN-T) to understand why such domains are widespread in toxins that target Gram-negative bacteria. Like some other intrinsically disordered proteins in the solution state of the protein, ColN-T shows dual recognition, initially interacting with other domains of the same colicin N molecule and later, during cell killing, binding to two different receptors, OmpF and TolA, in the target bacterium. ColN-T is invisible in the high-resolution x-ray model and yet accounts for 90 of the toxin's 387 amino acid residues. To reveal its solution structure that underlies such a dynamic and complex system, we carried out mutagenic, biochemical, hydrodynamic and structural studies using analytical ultracentrifugation, NMR, and small-angle x-ray scattering on full-length ColN and its fragments. The structure was accurately modeled from small-angle x-ray scattering data by treating ColN as a flexible system, namely by the ensemble optimization method, which enables a distribution of conformations to be included in the final model. The results reveal, to our knowledge, for the first time the dynamic structure of a colicin T-domain. ColN-T is in dynamic equilibrium between a compact form, showing specific self-recognition and resistance to proteolysis, and an extended form, which most likely allows for effective receptor binding.
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Colicinas/metabolismo , Sequência de Aminoácidos , Antibacterianos/química , Antibacterianos/metabolismo , Colicinas/química , Colicinas/genética , Elasticidade , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Hidrodinâmica , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Proteínas de Membrana , Modelos Moleculares , Mutação , Ressonância Magnética Nuclear Biomolecular , Porinas/química , Porinas/metabolismo , Conformação Proteica , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae , Espalhamento a Baixo Ângulo , Soluções/química , Ultracentrifugação , Difração de Raios XRESUMO
Results are reported from a search for supersymmetric particles in proton-proton collisions in the final state with a single lepton, multiple jets, including at least one b-tagged jet, and large missing transverse momentum. The search uses a sample of proton-proton collision data at sqrt[s]=13 TeV recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 35.9 fb^{-1}. The observed event yields in the signal regions are consistent with those expected from standard model backgrounds. The results are interpreted in the context of simplified models of supersymmetry involving gluino pair production, with gluino decay into either on- or off-mass-shell top squarks. Assuming that the top squarks decay into a top quark plus a stable, weakly interacting neutralino, scenarios with gluino masses up to about 1.9 TeV are excluded at 95% confidence level for neutralino masses up to about 1 TeV.
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A search is reported for a narrow vector resonance decaying to quark-antiquark pairs in proton-proton collisions at sqrt[s]=13 TeV, collected with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 2.7 fb^{-1}. The vector resonance is produced at large transverse momenta, with its decay products merged into a single jet. The resulting signature is a peak over background in the distribution of the invariant mass of the jet. The results are interpreted in the framework of a leptophobic vector resonance and no evidence is found for such particles in the mass range of 100-300 GeV. Upper limits at 95% confidence level on the production cross section are presented in a region of mass-coupling phase space previously unexplored at the LHC. The region below 140 GeV has not been explored by any previous experiments.
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A search for a signal consistent with the type-III seesaw mechanism in events with three or more electrons or muons is presented. The data sample consists of proton-proton collisions at sqrt[s]=13 TeV collected by the CMS experiment at the LHC in 2016 and corresponds to an integrated luminosity of 35.9 fb^{-1}. Selection criteria based on the number of leptons and the invariant mass of oppositely charged lepton pairs are used to distinguish the signal from the standard model background. The observations are consistent with the expectations from standard model processes. The results are used to place limits on the production of heavy fermions of the type-III seesaw model as a function of the branching ratio to each lepton flavor. In the scenario of equal branching fractions to each lepton flavor, heavy fermions with masses below 840 GeV are excluded. This is the most sensitive probe to date of the type-III seesaw mechanism.
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The first observation of top quark production in proton-nucleus collisions is reported using proton-lead data collected by the CMS experiment at the CERN LHC at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=8.16 TeV. The measurement is performed using events with exactly one isolated electron or muon candidate and at least four jets. The data sample corresponds to an integrated luminosity of 174 nb^{-1}. The significance of the tt[over ¯] signal against the background-only hypothesis is above 5 standard deviations. The measured cross section is σ_{tt[over ¯]}=45±8 nb, consistent with predictions from perturbative quantum chromodynamics.
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Over the last two decades many secrets of the age-related human neural proteinopathies have been revealed. A common feature of these diseases is abnormal, and possibly pathogenic, aggregation of specific proteins in the effected tissue often resulting from inherent or decreased structural stability. An archetype example of this is superoxide dismutase-1, the first genetic factor to be linked with amyotrophic lateral sclerosis (ALS). Mutant or posttranslationally modified TAR DNA binding protein-32 (TDP-43) is also strongly associated with ALS and an increasingly large number of other neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD). Cytoplasmic mislocalization and elevated half-life is a characteristic of mutant TDP-43. Furthermore, patient age at the onset of disease symptoms shows a good inverse correlation with mutant TDP-43 half-life. Here we show that ALS and FTLD-associated TDP-43 mutations in the central nucleic acid binding domains lead to elevated half-life and this is commensurate with increased thermal stability and inhibition of aggregation. It is achieved without impact on secondary, tertiary, or quaternary structure. We propose that tighter structural cohesion contributes to reduced protein turnover, increasingly abnormal proteostasis and, ultimately, faster onset of disease symptoms. These results contrast our perception of neurodegenerative diseases as misfolded proteinopathies and delineate a novel path from the molecular characteristics of mutant TDP-43 to aberrant cellular effects and patient phenotype.
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Proteínas de Ligação a DNA/genética , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/genética , Fluorescência , Meia-Vida , Humanos , Mutação/genética , Doenças Neurodegenerativas/fisiopatologia , Estabilidade Proteica , Espalhamento a Baixo ÂnguloRESUMO
Proteins that contain a distinct knot in their native structure are impressive examples of biological self-organization. Although this topological complexity does not appear to cause a folding problem, the mechanisms by which such knotted proteins form are unknown. We found that the fusion of an additional protein domain to either the amino terminus, the carboxy terminus, or to both termini of two small knotted proteins did not affect their ability to knot. The multidomain constructs remained able to fold to structures previously thought unfeasible, some representing the deepest protein knots known. By examining the folding kinetics of these fusion proteins, we found evidence to suggest that knotting is not rate limiting during folding, but instead occurs in a denatured-like state. These studies offer experimental insights into when knot formation occurs in natural proteins and demonstrate that early folding events can lead to diverse and sometimes unexpected protein topologies.
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Dobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Archaeoglobus fulgidus/química , Archaeoglobus fulgidus/genética , Dimerização , Escherichia coli/química , Escherichia coli/genética , Haemophilus influenzae/química , Haemophilus influenzae/genética , Metiltransferases/química , Metiltransferases/genética , Metiltransferases/metabolismo , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/genética , Ureia/farmacologiaRESUMO
Talin is a 270-kDa protein that activates integrins and couples them to cytoskeletal actin. Talin contains an N-terminal FERM domain comprised of F1, F2 and F3 domains, but it is atypical in that F1 contains a large insert and is preceded by an extra domain F0. Although F3 contains the binding site for beta-integrin tails, F0 and F1 are also required for activation of beta1-integrins. Here, we report the solution structures of F0, F1 and of the F0F1 double domain. Both F0 and F1 have ubiquitin-like folds joined in a novel fixed orientation by an extensive charged interface. The F1 insert forms a loop with helical propensity, and basic residues predicted to reside on one surface of the helix are required for binding to acidic phospholipids and for talin-mediated activation of beta1-integrins. This and the fact that basic residues on F2 and F3 are also essential for integrin activation suggest that extensive interactions between the talin FERM domain and acidic membrane phospholipids are required to orientate the FERM domain such that it can activate integrins.
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Integrinas/metabolismo , Talina/química , Ubiquitina/química , Sequência de Aminoácidos , Sítios de Ligação , Adesão Celular , Integrinas/química , Modelos Moleculares , Dados de Sequência Molecular , Dobramento de Proteína , Estrutura Terciária de Proteína , Talina/metabolismo , Ubiquitina/metabolismoRESUMO
INTRODUCTION: Standard brain magnetic resonance imaging (MRI) is typically normal in most patients after mild traumatic brain injury (MTBI). Proton magnetic resonance spectroscopy (¹H-MRS) is more sensitive to detect subtle post-traumatic changes. The aim of the study was to evaluate the clinical correlations of these changes in the acute phase (within 3 days) after MTBI. METHODS: Twenty-one patients with MTBI and 22 controls were studied. Both groups underwent neuropsychological testing and single-voxel ¹H-MRS examination of both frontal lobes and upper brainstem. RESULTS: Significant decrease in NAA was found in both frontal lobes and in NAA/Cre ratio in the right frontal lobe (p < 0.05). Correlation analysis showed a correlation of NAA in the left frontal lobe with Backward Digit Span (p = 0.022) and Stroop test A (p = 0.0034) and a weak correlation with TMT B time (p = 0.046). The NAA/Cre in the right frontal lobe correlated with Stroop test A (p = 0.007) and with the total score of Digit Span (p = 0.016). Lower NAA was found in the upper brainstem (p = 0.0157) in the sub-group of patients with post-traumatic unconsciousness. CONCLUSIONS: This study found a correlation of ¹H-MRS metabolite changes with cognitive decline and presence or absence of loss of consciousness in the acute phase after MTBI.
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Ácido Aspártico/análogos & derivados , Lesões Encefálicas/patologia , Transtornos Cognitivos/patologia , Creatina/metabolismo , Lobo Frontal/patologia , Espectroscopia de Prótons por Ressonância Magnética , Adulto , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Lesões Encefálicas/complicações , Transtornos Cognitivos/etiologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sensibilidade e EspecificidadeRESUMO
The biosynthesis of chlorophyll, an essential cofactor for photosynthesis, requires the ATP-dependent insertion of Mg(2+) into protoporphyrin IX catalyzed by the multisubunit enzyme magnesium chelatase. This enzyme complex consists of the I subunit, an ATPase that forms a complex with the D subunit, and an H subunit that binds both the protoporphyrin substrate and the magnesium protoporphyrin product. In this study we used electron microscopy and small-angle x-ray scattering to investigate the structure of the magnesium chelatase H subunit, ChlH, from the thermophilic cyanobacterium Thermosynechococcus elongatus. Single particle reconstruction of negatively stained apo-ChlH and Chl-porphyrin proteins was used to reconstitute three-dimensional structures to a resolution of â¼30 Å. ChlH is a large, 148-kDa protein of 1326 residues, forming a cage-like assembly comprising the majority of the structure, attached to a globular N-terminal domain of â¼16 kDa by a narrow linker region. This N-terminal domain is adjacent to a 5 nm-diameter opening in the structure that allows access to a cavity. Small-angle x-ray scattering analysis of ChlH, performed on soluble, catalytically active ChlH, verifies the presence of two domains and their relative sizes. Our results provide a basis for the multiple regulatory and catalytic functions of ChlH of oxygenic photosynthetic organisms and for a chaperoning function that sequesters the enzyme-bound magnesium protoporphyrin product prior to its delivery to the next enzyme in the chlorophyll biosynthetic pathway, magnesium protoporphyrin methyltransferase.