Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The P5-type ATPase ATP13A1 modulates major histocompatibility complex I-related protein 1 (MR1)-mediated antigen presentation

The monomorphic antigen-presenting molecule major histocompatibility complex-I-related protein 1 (MR1) presents small-molecule metabolites to mucosal-associated invariant T (MAIT) cells. The MR1-MAIT cell axis has been implicated in a variety of infectious and noncommunicable diseases, and recent studies have begun to develop an understanding of the molecular mechanisms underlying this specialized antigen presentation pathway. However, proteins regulating MR1 folding, loading, stability, and surface expression remain to be identified. Here, we performed a gene trap screen to discover novel modulators of MR1 surface expression through insertional mutagenesis of an MR1-overexpressing clone derived from the near-haploid human cell line HAP1 (HAP1.MR1). The most significant positive regulators identified included β(2)-microglobulin, a known regulator of MR1 surface expression, and ATP13A1, a P5-type ATPase in the endoplasmic reticulum (ER) not previously known to be associated with MR1-mediated antigen presentation. CRISPR/Cas9-mediated knockout of ATP13A1 in both HAP1.MR1 and THP-1 cell lines revealed a profound reduction in MR1 protein levels and a concomitant functional defect specific to MR1-mediated antigen presentation. Collectively, these data are consistent with the ER-resident ATP13A1 being a key posttranscriptional determinant of MR1 surface expression

The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial

We thank the Oxford Genomics Centre at the Wellcome Centre for Human Genetics (funded by Wellcome Trust grant reference 203141/Z/16/Z) for the generation and initial processing of the sequencing data. This work was funded in part by NuCana plc. The Oxford Early Phase Clinical Trials Unit, the Edinburgh and Newcastle Trials units are grateful for support from CRUK and Experimental Cancer Medicine Centre (ECMC) funding.Purpose: Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate cap. ProTides are easily incorporated into cells whereupon the cap is cleaved and a pre-activated nucleoside released. 3'-deoxyadenosine (3'-dA) is a naturally-occurring adenosine analogue with established anti-cancer activity in vitro but limited bioavailability due to its rapid in vivo deamination by the circulating enzyme adenosine deaminase, poor uptake into cells and reliance on adenosine kinase for its activation. In order to overcome these limitations, 3'-dA was chemically modified to create the novel ProTide NUC-7738. Experimental Design: We describe the synthesis of NUC-7738. We determine the IC50 of NUC-7738 using pharmacokinetics (PK) and conduct genome-wide analyses to identify its mechanism of action using different cancer model systems. We validate these findings in cancer patients. Results: We show that NUC-7738 overcomes the cancer resistance mechanisms that limit the activity of 3'-dA and that its activation is dependent on ProTide cleavage by the enzyme histidine triad nucleotide binding protein 1. PK and tumour samples obtained from the ongoing first-in-human Phase 1 clinical trial of NUC-7738 further validate our in vitro findings and show NUC-7738 is an effective pro-apoptotic agent in cancer cells with effects on the NF-kappaB pathway. Conclusions: Our study provides proof that NUC-7738 overcomes cellular resistance mechanisms and support its further clinical evaluation as a novel cancer treatment within the growing pantheon of anti-cancer ProTides.Publisher PDFPeer reviewe

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$

Measurement of the prompt D0D^0 nuclear modification factor in ppPb collisions at sNN=8.16\sqrt{s_\mathrm{NN}} = 8.16 TeV

International audienceThe production of prompt $D^0$ mesons in proton-lead collisions in the forward and backward configurations at a center-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}} = 8.16~\mathrm{TeV}$ is measured by the LHCb experiment. The nuclear modification factor of prompt $D^0$ mesons is determined as a function of the transverse momentum $p_\mathrm{T}$, and rapidity in the nucleon-nucleon center-of-mass frame $y^*$. In the forward rapidity region, significantly suppressed production with respect to $pp$ collisions is measured, which provides significant constraints of nuclear parton distributions and hadron production down to the very low Bjorken-$x$ region of $\sim 10^{-5}$. In the backward rapidity region, a suppression with a significance of 2.0 - 3.8 standard deviations compared to nPDF expectations is found in the kinematic region of $p_\mathrm{T}>6~\mathrm{GeV}/c$ and $-3.25<y^*<-2.5$, corresponding to $x\sim 0.01$

Amplitude analysis of the Λc+→pK−π+\Lambda^+_c\to pK^-\pi^+ decay and Λc+\Lambda^+_c baryon polarization measurement in semileptonic beauty hadron decays

An amplitude analysis of $\Lambda^+_c \to pK^-\pi^+$ decays together with a measurement of the $\Lambda^+_c$ polarization vector in semileptonic beauty hadron decays is presented. A sample of $400\,000$ candidates is selected from proton-proton collisions recorded by the LHCb detector at a center-of-mass energy of 13 TeV. An amplitude model is developed and the resonance fractions as well as two- and three-body decay parameters are reported. The mass and width of the $\Lambda(2000)$ state are also determined. A significant $\Lambda^+_c$ polarization is found. A large sensitivity of the $\Lambda^+_c \to pK^-\pi^+$ decay to the polarization is seen, making the amplitude model suitable for $\Lambda^+_c$ polarization measurements in other systems.An amplitude analysis of Λc+→pK-π+ decays together with a measurement of the Λc+ polarization vector in semiōleptonic beauty hadron decays is presented. A sample of 400 000 candidates is selected from proton-proton collisions recorded by the LHCb detector at a center-of-mass energy of 13 TeV. An amplitude model is developed and the resonance fractions as well as two- and three-body decay parameters are reported. The mass and width of the Λ(2000) state are also determined. A significant Λc+ polarization is found. A large sensitivity of the Λc+→pK-π+ decay to the polarization is seen, making the amplitude model suitable for Λc+ polarization measurements in other systems.An amplitude analysis of $\Lambda^+_c \to pK^-\pi^+$ decays together with a measurement of the $\Lambda^+_c$ polarization vector in semileptonic beauty hadron decays is presented. A sample of $400\,000$ candidates is selected from proton-proton collisions recorded by the LHCb detector at a center-of-mass energy of 13 TeV. An amplitude model is developed and the resonance fractions as well as two- and three-body decay parameters are reported. The mass and width of the $\Lambda(2000)$ state are also determined. A significant $\Lambda^+_c$ polarization is found. A large sensitivity of the $\Lambda^+_c \to pK^-\pi^+$ decay to the polarization is seen, making the amplitude model suitable for $\Lambda^+_c$ polarization measurements in other systems