A full amplitude analysis of Λ0b→J/ψpπ− decays is performed with a data sample acquired with the LHCb detector from 7 and 8 TeV pp collisions, corresponding to an integrated luminosity of 3 fb−1. A ...significantly better description of the data is achieved when, in addition to the previously observed nucleon excitations N→pπ−, either the Pc(4380)+ and Pc(4450)+→J/ψp states, previously observed in Λ0b→J/ψpK− decays, or the Zc(4200)−→J/ψπ− state, previously reported in B0→J/ψK+π− decays, or all three, are included in the amplitude models. The data support a model containing all three exotic states, with a significance of more than three standard deviations. Within uncertainties, the data are consistent with the Pc(4380)+ and Pc(4450)+ production rates expected from their previous observation taking account of Cabibbo suppression.
The CP asymmetry in the mixing of B0s and B¯0s mesons is measured in proton-proton collision data corresponding to an integrated luminosity of 3.0 fb-1, recorded by the LHCb experiment at ...center-of-mass energies of 7 and 8 TeV. Semileptonic B0s and B¯0s decays are studied in the inclusive mode D∓sμ±ν(–)μX with the D∓s mesons reconstructed in the K+K–π∓ final state. Correcting the observed charge asymmetry for detection and background effects, the CP asymmetry is found to be assl = (0.39 ± 0.26 ± 0.20)%, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of assl to date. It is consistent with the prediction from the standard model and will constrain new models of particle physics.
A
bstract
The production of
W
and
Z
bosons in association with jets is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, ...corresponding to an integrated luminosity of 1.98 ± 0.02 fb
−1
. The
W
boson is identified using its decay to a muon and a neutrino, while the
Z
boson is identified through its decay to a muon pair. Total cross-sections are measured and combined into charge ratios, asymmetries, and ratios of
W
+jet and
Z
+jet production cross-sections. Differential measurements are also performed as a function of both boson and jet kinematic variables. All results are in agreement with Standard Model predictions.
A search for the decays Bc+→J/ψD(*)0K+ and Bc+→J/ψD(*)+K*0 is performed with data collected at the LHCb experiment corresponding to an integrated luminosity of 3 fb−1. The decays Bc+→J/ψD0K+ and ...Bc+→J/ψD*0K+ are observed for the first time, while first evidence is reported for the Bc+→J/ψD*+K*0 and Bc+→J/ψD+K*0 decays. The branching fractions of these decays are determined relative to the Bc+→J/ψπ+ decay. The Bc+ mass is measured, using the J/ψD0K+ final state, to be 6274.28±1.40(stat)±0.32(syst) MeV/c2. This is the most precise single measurement of the Bc+ mass to date.
The rise in the analytical speed of mutiparameter flow cytometers made possible by the introduction of digital instruments, has brought up the possibility to manage progressively higher number of ...parameters simultaneously on significantly greater numbers of individual cells. This has led to an exponential increase in the complexity and volume of flow cytometry data generated about cells present in individual samples evaluated in a single measurement. This increase demands for new developments in flow cytometry data analysis, graphical representation, and visualization and interpretation tools to address the new big data challenges, i.e. processing data files of ≥10–25 parameters per cell in samples with >5–10 million cells (= up to 250 million data points per cell sample) obtained in a few minutes.
Here, we present a comprehensive review of some of the tools developed by the EuroFlow consortium for processing flow cytometric big data files in diagnostic laboratories, particularly focused on automated EuroFlow approaches for: i) identification of all cell populations coexisting in a sample (automated gating); ii) smart classification of aberrant cell populations in routine diagnostics; iii) automated reporting; together with iv) new tools developed to visualize n-dimensional data in 2-dimensional plots to support expert-guided automated data analysis. The concept of using reference data bases implemented into software programs, in combination with multivariate statistical analysis pioneered by EuroFlow, provides an innovative, highly efficient and fast approach for diagnostic screening, classification and monitoring of patients with distinct hematological and immune disorders, as well as other diseases.
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel ...(T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.
Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL). However, ...data‐analysis remains mainly expert‐dependent. In this study, we designed and validated an Automated Gating & Identification (AGI) tool for MRD analysis in BCP‐ALL patients using the two tubes of the EuroFlow 8‐color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow‐up samples from 174 BCP‐ALL patients, stained with the EuroFlow BCP‐ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra‐expert concordance (100%) and good inter‐expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP‐ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.
Fibrinolytic proteases are a promising alternative in the pharmaceutical industry, they are used in the treatment of cardiovascular diseases, especially thrombosis. Microorganisms are the most ...interesting source of fibrinolytic proteases. The aim of this study was the production of fibrinolytic protease from Streptomyces parvulus DPUA 1573, the recovery of the protease by aqueous two-phase system and partial biochemical characterization of the enzyme. The aqueous two-phase system was performed according to a 24-full factorial design using polyethylene glycol molar mass, polyethylene glycol concentration, citrate concentration and pH as independent variables. It was analyzed the effect of different ions, surfactants, inhibitors, pH and temperature on enzyme activity. The best conditions for purifying the enzyme were 17.5% polyethylene glycol 8,000, 15% Phosphate and pH 8.0, it was obtained a partition coefficient of 7.33, a yield of 57.49% and a purification factor of 2.10-fold. There was an increase in enzyme activity in the presence of Fe2+ and a decrease in the presence of $\beta$-Mercaptoethanol, phenylmethylsulfonyl fluoride and Iodoacetic acid. The optimum pH was 7.0 and the optimum temperature was 40 ºC. The purified protease exhibited a molecular mass of 41 kDa. The fibrinolytic protease from Streptomyces parvulus proved to be a viable option for the development of a possible drug with fibrinolytic action.
A search for $CP$ violation in the decay $Λ^0_b$ → $pK$- $μ$+$μ$- is presented. This decay is mediated by flavour-changing neutral-current transitions in the Standard Model and is potentially ...sensitive to new sources of CP violation. The study is based on a data sample of proton-proton collisions recorded with the LHCb experiment, corresponding to an integrated luminosity of 3 fb-1. The $Λ^0_b$ → $pK$- $μ$+$μ$- decay is observed for the first time, and two observables that are sensitive to different manifestations of $CP$ violation are measured, $ΔΑ$CP $\equiv$ $ΔΑ$CP ($Λ^0_b$ → $pK$- $μ$+$μ$-) - $ΔΑ$CP($Λ^0_b$ → $pK$- $J/Ψ$) and a C P T ^ - o d d , where the latter is based on asymmetries in the angle between the $μ$+$μ$- and $pK$- decay planes. These are measured to be Δ A C P = ( − 3.5 ± 5.0 ( s t a t ) ± 0.2 ( s y s t ) ) × 10 − 2 , a C P T ^ - o d d = ( 1.2 ± 5.0 ( s t a t ) ± 0.7 ( s y s t ) ) × 10 − 2 , and no evidence for $CP$ violation is found
Mosaic segmental and whole chromosome copy number alterations are postzygotic variations known to be associated with several disorders. We have previously presented an efficient targeted sequencing ...approach to simultaneously detect point mutations and copy number variations (CNVs). In this study, we evaluated the efficiency of this approach to detect mosaic CNVs, using seven postnatal and 19 tumor samples, previously characterized by chromosomal microarray analyses (CMA). These samples harbored a total of 28 genomic imbalances ranging in size from 0.68 to 171 Mb, and present in 10–80% of the cells. All CNV regions covered by the platform were correctly identified in postnatal samples, and only seven out of 19 CNVs from tumor samples were not identified either because of a lack of target probes in the affected genomic regions or an absence of minimum reads for an alteration call. These results demonstrate that, in a research setting, this is a robust approach for detecting mosaicism in cases of segmental and whole chromosome alterations. Although the current sequencing platform presented a resolution similar to genomic microarrays, it is still necessary to further validate this approach in a clinical setting in order to replace CMA and sequencing analyses by a single test.
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