Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

BCL11A +58/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate.

Editing the +58 region of the BCL11A erythroid enhancer has shown promise in treating β-globin disorders. To address variations in fetal hemoglobin (HbF) response, we investigated editing both +58 and +55 enhancers. Rhesus macaques transplanted with edited hematopoietic stem/progenitor cells (HSPCs) following busulfan conditioning exhibited durable, high-level (∼90%) editing frequencies post transplantation with sustained HbF reactivation over 4 years, without hematological perturbations.

Search for Time-Dependent CP Violation in D^{0}→π^{+}π^{-}π^{0} Decays.

A measurement of time-dependent CP violation in D^{0}→π^{+}π^{-}π^{0} decays using a pp collision data sample collected by the LHCb experiment in 2012 and from 2015 to 2018, corresponding to an integrated luminosity of 7.7  fb^{-1}, is presented. The initial flavor of each D^{0} candidate is determined from the charge of the pion produced in the D^{*}(2010)^{+}→D^{0}π^{+} decay.

Scalable assessment of genome editing off-targets associated with genetic variants.

Genome editing with RNA-guided DNA binding factors carries risk of off-target editing at homologous sequences. Genetic variants may introduce sequence changes that increase homology to a genome editing target, thereby increasing risk of off-target editing. Conventional methods to verify candidate off-targets rely on access to cells with genomic DNA carrying these sequences.

Modification of χ_{c1}(3872) and ψ(2S) Production in pPb Collisions at sqrt[s_{NN}]=8.16 TeV.

The LHCb Collaboration measures production of the exotic hadron χ_{c1}(3872) in proton-nucleus collisions for the first time. Comparison with the charmonium state ψ(2S) suggests that the exotic χ_{c1}(3872) experiences different dynamics in the nuclear medium than conventional hadrons, and comparison with data from proton-proton collisions indicates that the presence of the nucleus may modify χ_{c1}(3872) production rates. This is the first measurement of the nuclear modification factor of an exotic hadron.

Amplitude Analysis of the B^{0}→K^{*0}μ^{+}μ^{-} Decay.

An amplitude analysis of the B^{0}→K^{*0}μ^{+}μ^{-} decay is presented using a dataset corresponding to an integrated luminosity of 4.7  fb^{-1} of pp collision data collected with the LHCb experiment. For the first time, the coefficients associated to short-distance physics effects, sensitive to processes beyond the standard model, are extracted directly from the data through a q^{2}-unbinned amplitude analysis, where q^{2} is the μ^{+}μ^{-} invariant mass squared.

Fraction of χ_{c} Decays in Prompt J/ψ Production Measured in pPb Collisions at sqrt[s_{NN}]=8.16 TeV.

The fraction of χ_{c1} and χ_{c2} decays in the prompt J/ψ yield, F_{χ_{c}→J/ψ}=σ_{χ_{c}→J/ψ}/σ_{J/ψ}, is measured by the LHCb detector in pPb collisions at sqrt[s_{NN}]=8.16  TeV. The study covers the forward (1.

Observation of Cabibbo-Suppressed Two-Body Hadronic Decays and Precision Mass Measurement of the Ω_{c}^{0} Baryon.

The first observation of the singly Cabibbo-suppressed Ω_{c}^{0}→Ω^{-}K^{+} and Ω_{c}^{0}→Ξ^{-}π^{+} decays is reported, using proton-proton collision data at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5.4  fb^{-1}, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be B(Ω_{c}^{0}→Ω^{-}K^{+})/B(Ω_{c}^{0}→Ω^{-}π^{+})=[6.

Enhanced Production of Λ_{b}^{0} Baryons in High-Multiplicity pp Collisions at sqrt[s]=13 TeV.

The production rate of Λ_{b}^{0} baryons relative to B^{0} mesons in pp collisions at a center-of-mass energy sqrt[s]=13  TeV is measured by the LHCb experiment. The ratio of Λ_{b}^{0} to B^{0} production cross sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in e^{+}e^{-} collisions, and increases by a factor of ∼2 with increasing multiplicity.

Histone variant H2A.Z and linker histone H1 influence chromosome condensation in Saccharomyces cerevisiae.

Chromosome condensation is essential for the fidelity of chromosome segregation during mitosis and meiosis. Condensation is associated both with local changes in nucleosome structure and larger-scale alterations in chromosome topology mediated by the condensin complex. We examined the influence of linker histone H1 and variant histone H2A.

Improved Measurement of CP Violation Parameters in B_{s}^{0}→J/ψK^{+}K^{-} Decays in the Vicinity of the ϕ(1020) Resonance.

The decay-time-dependent CP asymmetry in B_{s}^{0}→J/ψ(→μ^{+}μ^{-})K^{+}K^{-} decays is measured using proton-proton collision data, corresponding to an integrated luminosity of 6  fb^{-1}, collected with the LHCb detector at a center-of-mass energy of 13 TeV. Using a sample of approximately 349 000 B_{s}^{0} signal decays with an invariant K^{+}K^{-} mass in the vicinity of the ϕ(1020) resonance, the CP-violating phase ϕ_{s} is measured, along with the difference in decay widths of the light and heavy mass eigenstates of the B_{s}^{0}-B[over ¯]_{s}^{0} system, ΔΓ_{s}, and the difference of the average B_{s}^{0} and B^{0} meson decay widths, Γ_{s}-Γ_{d}. The values obtained are ϕ_{s}=-0.

Measurement of CP Violation in B^{0}→ψ(→ℓ^{+}ℓ^{-})K_{S}^{0}(→π^{+}π^{-}) Decays.

A measurement of time-dependent CP violation in the decays of B^{0} and B[over ¯]^{0} mesons to the final states J/ψ(→μ^{+}μ^{-})K_{S}^{0}, ψ(2S)(→μ^{+}μ^{-})K_{S}^{0} and J/ψ(→e^{+}e^{-})K_{S}^{0} with K_{S}^{0}→π^{+}π^{-} is presented. The data correspond to an integrated luminosity of 6  fb^{-1} collected at a center-of-mass energy of sqrt[s]=13  TeV with the LHCb detector. The CP-violation parameters are measured to be S_{ψK_{S}^{0}}=0.

Search for Evidence of Baryogenesis and Dark Matter in B^{+}→ψ_{D}+p Decays at BABAR.

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment.

Precision Measurement of CP Violation in the Penguin-Mediated Decay B_{s}^{0}→ϕϕ.

A flavor-tagged time-dependent angular analysis of the decay B_{s}^{0}→ϕϕ is performed using pp collision data collected by the LHCb experiment at the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb^{-1}. The CP-violating phase and direct CP-violation parameter are measured to be ϕ_{s}^{ss[over ¯]s}=-0.042±0.

Observation of New Baryons in the Ξ_{b}^{-}π^{+}π^{-} and Ξ_{b}^{0}π^{+}π^{-} Systems.

The first observation and study of two new baryonic structures in the final state Ξ_{b}^{0}π^{+}π^{-} and the confirmation of the Ξ_{b}(6100)^{-} state in the Ξ_{b}^{-}π^{+}π^{-} decay mode are reported using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9  fb^{-1}. In addition, the properties of the known Ξ_{b}^{*0}, Ξ_{b}^{'-} and Ξ_{b}^{*-} resonances are measured with improved precision. The new decay mode of the Ξ_{b}^{0} baryon to the Ξ_{c}^{+} π^{-} π^{+} π^{-} final state is observed and exploited for the first time in these measurements.

Measurement of the Λ_{b}^{0}→Λ(1520)μ^{+}μ^{-} Differential Branching Fraction.

The branching fraction of the rare decay Λ_{b}^{0}→Λ(1520)μ^{+}μ^{-} is measured for the first time, in the squared dimuon mass intervals q^{2}, excluding the J/ψ and ψ(2S) regions. The data sample analyzed was collected by the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV, corresponding to a total integrated luminosity of 9  fb^{-1}. The result in the highest q^{2} interval, q^{2}>15.

Evidence of a J/ψK_{S}^{0} Structure in B^{0}→J/ψϕK_{S}^{0} Decays.

An amplitude analysis of B^{0}→J/ψϕK_{S}^{0} decays is performed using proton-proton collision data, corresponding to an integrated luminosity of 9  fb^{-1}, collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV. Evidence with a significance of 4.0 standard deviations of a structure in the J/ψK_{S}^{0} system, named T_{ψs1}^{θ}(4000)^{0}, is seen, with its mass and width measured to be 3991_{-10}^{+12} _{-17}^{+9}  MeV/c^{2} and 105_{-25}^{+29} _{-23}^{+17}  MeV, respectively, where the first uncertainty is statistical and the second systematic.

Observation of New Ω_{c}^{0} States Decaying to the Ξ_{c}^{+}K^{-} Final State.

Two new excited states, Ω_{c}(3185)^{0} and Ω_{c}(3327)^{0}, are observed in the Ξ_{c}^{+}K^{-} invariant-mass spectrum using proton-proton collision data collected by the LHCb experiment, corresponding to an integrated luminosity of 9  fb^{-1}. Five previously observed excited Ω_{c}^{0} states are confirmed, namely Ω_{c}(3000)^{0}, Ω_{c}(3050)^{0}, Ω_{c}(3065)^{0}, Ω_{c}(3090)^{0}, and Ω_{c}(3119)^{0}. The masses and widths of these seven states are measured with the highest precision to date.

Measurement of the Ratios of Branching Fractions R(D^{*}) and R(D^{0}).

The ratios of branching fractions R(D^{*})≡B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}μ^{-}ν[over ¯]_{μ}) and R(D^{0})≡B(B^{-}→D^{0}τ^{-}ν[over ¯]_{τ})/B(B^{-}→D^{0}μ^{-}ν[over ¯]_{μ}) 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 τ^{-}→μ^{-}ν_{τ}ν[over ¯]_{μ}.

Measurement of the Time-Integrated CP Asymmetry in D^{0}→K^{-}K^{+} Decays.

The time-integrated CP asymmetry in the Cabibbo-suppressed decay D^{0}→K^{-}K^{+} is measured using proton-proton collision data, corresponding to an integrated luminosity of 5.7  fb^{-1} collected at a center-of-mass energy of 13 TeV with the LHCb detector. The D^{0} mesons are required to originate from promptly produced D^{*+}→D^{0}π^{+} decays, and the charge of the companion pion is used to determine the flavor of the charm meson at production.

Measurement of the Branching Fractions B(B^{0}→pp[over ¯]pp[over ¯]) and B(B_{s}^{0}→pp[over ¯]pp[over ¯]).

Searches for the rare hadronic decays B^{0}→pp[over ¯]pp[over ¯] and B_{s}^{0}→pp[over ¯]pp[over ¯] are performed using proton-proton collision data recorded by the LHCb experiment and corresponding to an integrated luminosity of 9  fb^{-1}. Significances of 9.3σ and 4.

Observation of a Resonant Structure near the D_{s}^{+}D_{s}^{-} Threshold in the B^{+}→D_{s}^{+}D_{s}^{-}K^{+} Decay.

An amplitude analysis of the B^{+}→D_{s}^{+}D_{s}^{-}K^{+} decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at center-of-mass energies of 7, 8, and 13 TeV. A near-threshold peaking structure, referred to as X(3960), is observed in the D_{s}^{+}D_{s}^{-} invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width, and the quantum numbers of the structure are measured to be 3956±5±10  MeV, 43±13±8  MeV, and J^{PC}=0^{++}, respectively, where the first uncertainties are statistical and the second systematic.