Regulatory T cells in melanoma revisited by a computational clustering of FOXP3+ T cell subpopulations

CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Treg). FOXP3+ T cells are reported to be increased in tumour-bearing patients or animals, and considered to suppress anti-tumour immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation, and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumour immunity, but the arbitrariness and complexity of manual gating have complicated the issue. Here we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analysing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally-identified FOXP3+ subpopulation included not only classical FOXP3high Treg but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analysed an independent dataset, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Treg

Persistent Homology Over Directed Acyclic Graphs

We define persistent homology groups over any set of spaces which have inclusions defined so that the corresponding directed graph between the spaces is acyclic, as well as along any subgraph of this directed graph. This method simultaneously generalizes standard persistent homology, zigzag persistence and multidimensional persistence to arbitrary directed acyclic graphs, and it also allows the study of more general families of topological spaces or point-cloud data. We give an algorithm to compute the persistent homology groups simultaneously for all subgraphs which contain a single source and a single sink in $O(n^4)$ arithmetic operations, where $n$ is the number of vertices in the graph. We then demonstrate as an application of these tools a method to overlay two distinct filtrations of the same underlying space, which allows us to detect the most significant barcodes using considerably fewer points than standard persistence.Comment: Revised versio

Polarised target for Drell-Yan experiment in COMPASS at CERN, part I

In the polarised Drell-Yan experiment at the COMPASS facility in CERN pion beam with momentum of 190 GeV/c and intensity about $10^8$ pions/s interacted with transversely polarised NH$_3$ target. Muon pairs produced in Drel-Yan process were detected. The measurement was done in 2015 as the 1st ever polarised Drell-Yan fixed target experiment. The hydrogen nuclei in the solid-state NH$_3$ were polarised by dynamic nuclear polarisation in 2.5 T field of large-acceptance superconducting magnet. Large helium dilution cryostat was used to cool the target down below 100 mK. Polarisation of hydrogen nuclei reached during the data taking was about 80 %. Two oppositely polarised target cells, each 55 cm long and 4 cm in diameter were used. Overview of COMPASS facility and the polarised target with emphasis on the dilution cryostat and magnet is given. Results of the polarisation measurement in the Drell-Yan run and overviews of the target material, cell and dynamic nuclear polarisation system are given in the part II.Comment: 4 pages, 2 figures, Proceedings of the 22nd International Spin Symposium, Urbana-Champaign, Illinois, USA, 25-30 September 201

Development of Hydrophones for Detecting High-Energy Reactions in Water(III. Accelerator, Synchrotron Radiation, and Instrumentation)

Acoustic detectors were developed using a piezo ceramic compound PZT. A shape of the PZT detector was essential to obtain a high sensitivity. A detector of a spherically shaped shell structure, whose size was 50 mm in diameter and 2 mm thick, was fabricated. Its sensitivity was calibrated to be about 40 mV/Pa at 54 kHz. Using the hydrophone, acoustic signals generated by an electron-induced cascade shower in water were detected. Experimental results were compared with simulation data and confirmed a consistency in between

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Longitudinal double spin asymmetries in single hadron quasi-real photoproduction at high pTp_T

We measured the longitudinal double spin asymmetries $A_{LL}$ for single hadron muo-production off protons and deuterons at photon virtuality $Q^2$ < 1(GeV/$\it c$)$^2$ for transverse hadron momenta $p_T$ in the range 0.7 GeV/$\it c$ to 4 GeV/$\it c$ . They were determined using COMPASS data taken with a polarised muon beam of 160 GeV/$\it c$ or 200 GeV/$\it c$ impinging on polarised $\mathrm{{}^6LiD}$ or $\mathrm{NH_3}$ targets. The experimental asymmetries are compared to next-to-leading order pQCD calculations, and are sensitive to the gluon polarisation $\Delta G$ inside the nucleon in the range of the nucleon momentum fraction carried by gluons $0.05 < x_g < 0.2$

Interplay among transversity induced asymmetries in hadron leptoproduction

In the fragmentation of a transversely polarized quark several left-right asymmetries are possible for the hadrons in the jet. When only one unpolarized hadron is selected, it exhibits an azimuthal modulation known as Collins effect. When a pair of oppositely charged hadrons is observed, three asymmetries can be considered, a di-hadron asymmetry and two single hadron asymmetries. In lepton deep inelastic scattering on transversely polarized nucleons all these asymmetries are coupled with the transversity distribution. From the high statistics COMPASS data on oppositely charged hadron-pair production we have investigated for the first time the dependence of these three asymmetries on the difference of the azimuthal angles of the two hadrons. The similarity of transversity induced single and di-hadron asymmetries is discussed. A new analysis of the data allows to establish quantitative relationships among them, providing for the first time strong experimental indication that the underlying fragmentation mechanisms are all driven by a common physical process.Comment: 6 figure

Interplay among transversity induced asymmetries in hadron leptoproduction

In the fragmentation of a transversely polarized quark several left-right asymmetries are possible for the hadrons in the jet. When only one unpolarized hadron is selected, it exhibits an azimuthal modulation known as Collins effect. When a pair of oppositely charged hadrons is observed, three asymmetries can be considered, a di-hadron asymmetry and two single hadron asymmetries. In lepton deep inelastic scattering on transversely polarized nucleons all these asymmetries are coupled with the transversity distribution. From the high statistics COMPASS data on oppositely charged hadron-pair production we have investigated for the first time the dependence of these three asymmetries on the difference of the azimuthal angles of the two hadrons. The similarity of transversity induced single and di-hadron asymmetries is discussed. A new analysis of the data allows to establish quantitative relationships among them, providing for the first time strong experimental indication that the underlying fragmentation mechanisms are all driven by a common physical process.Comment: 6 figure

Resonance Production and ππ\pi\pi S-wave in π−+p→π−π−π++precoil\pi^- + p \rightarrow \pi^- \pi^- \pi^+ + p_{recoil} at 190 GeV/c

The COMPASS collaboration has collected the currently largest data set on diffractively produced $\pi^-\pi^-\pi^+$ final states using a negative pion beam of 190 GeV/c momentum impinging on a stationary proton target. This data set allows for a systematic partial-wave analysis in 100 bins of three-pion mass, $0.5 < m_{3\pi} < 2.5$ GeV/c$^2$ , and in 11 bins of the reduced four-momentum transfer squared, $0.1 < t < 1.0$ (GeV/c)$^2$ . This two-dimensional analysis offers sensitivity to genuine one-step resonance production, i.e. the production of a state followed by its decay, as well as to more complex dynamical effects in nonresonant $3\pi$ production. In this paper, we present detailed studies on selected $3\pi$ partial waves with $J^{PC} = 0^{-+}$, $1^{++}$, $2^{-+}$, $2^{++}$, and $4^{++}$. In these waves, we observe the well-known ground-state mesons as well as a new narrow axial-vector meson $a_1(1420)$ decaying into $f_0(980) \pi$. In addition, we present the results of a novel method to extract the amplitude of the $\pi^-\pi^+$ subsystem with $I^{G}J^{PC} = 0^+ 0^{++}$ in various partial waves from the $\pi^-\pi^-\pi^+$ data. Evidence is found for correlation of the $f_0(980)$ and $f_0(1500)$ appearing as intermediate $\pi^- \pi^+$ isobars in the decay of the known $\pi(1800)$ and $\pi_2(1880)$.Comment: 96 page