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

Tsunami waveform analyses of the 2006 underthrust and 2007 outer-rise Kurile earthquakes

International audienceThe 2006 large interplate Kurile earthquake proved that the entire plate interface of the Kurile-Kamchatka subduction zone was strongly coupled from Hokkaido, Japan, to Kamchatka, Russia. The seismic moment of the 2006 Kurile earthquake estimated from ten tsunami waveforms is 3.1×1021 Nm (Mw=8.3). This estimate is consistent with the seismic moment estimated from the seismological data in the Global CMT catalog. The computed tsunami propagation indicates that scattering of the tsunami waves occurred at the shallow region near the Emperor Ridge. The computed tsunami propagation also indicates that large later tsunami waves observed at Crescent City is caused by the shallow region along the Mendocino Fracture Zone. The seismic moment of the 2007 outer-rise Kurile earthquake estimated from tsunami waveforms is 1.0×1021 Nm (Mw=8.0). This estimate is also consistent with the seismic moment in the Global CMT catalog

Prognostic Factors in Cutaneous Squamous Cell Carcinoma: Is Patient Delay in Hospital Visit a Predictor of Survival?

The patient's delay in the visit to a hospital seems to play an important role in prognosis in invasive cutaneous squamous cell carcinoma (SCC). This report explored prognostic factors of cutaneous SCC focusing on patient delay in hospital visit. Data of 117 Japanese patients who were treated for invasive cutaneous SCC in our facility between 2000 and 2010 were used for analysis. A multivariate Cox proportional-hazard modelling revealed that a pair of TNM stage (hazard ratio, 5.0; 95% CI, 1.8 to 13.9) and poorer histological differentiation (hazard ratio, 3.2; 95% CI, 0.93 to 10.3), and a pair of tumour size (hazard ratio, 1.02; 95% CI, 1.004 to 1.04) and rapid growth (hazard ratio, 8.25; 95% CI, 1.29 to 52.7) were a prognostic factor whereas patient delay in hospital visit was not. However, patient delay in hospital visit was correlated with larger tumour size

Z7Z_7 Orbifold Models in M-Theory

Among $T^7/\Gamma$ orbifold compactifications of $M$-theory, we examine models containing the particle physics Standard Model in four-dimensional spacetimes, which appear as fixed subspaces of the ten-dimensional spacetimes at each end of the interval, $I^1\simeq S^1/Z_2$, spanning the $11^\text{th}$ dimension. Using the $Z_7$ projection to break the $E_8$ gauge symmetry in each of the four-planes and a limiting relation to corresponding heterotic string compactifications, we discuss the restrictions on the possible resulting gauge field and matter spectra. In particular, some of the states are non-local: they connect two four-dimensional Worlds across the $11^\text{th}$ dimension. We illustrate our programmable calculations of the matter field spectrum, including the anomalous U(1) factor which satisfies a universal Green-Schwarz relation, discuss a Dynkin diagram technique to showcase a model with $SU(3)\times SU(2)\times U(1)^5$ gauge symmetry, and discuss generalizations to higher order orbifolds.Comment: 23 pages, 2 figures, 4 tables; LaTeX 3 time

Prospects for improving the sensitivity of KAGRA gravitational wave detector

KAGRA is a new gravitational wave detector which aims to begin joint observation with Advanced LIGO and Advanced Virgo from late 2019. Here, we present KAGRA's possible upgrade plans to improve the sensitivity in the decade ahead. Unlike other state-of-the-art detectors, KAGRA requires different investigations for the upgrade since it is the only detector which employs cryogenic cooling of the test mass mirrors. In this paper, investigations on the upgrade plans which can be realized by changing the input laser power, increasing the mirror mass, and injecting frequency dependent squeezed vacuum are presented. We show how each upgrade affects to the detector frequency bands and also discuss impacts on gravitational-wave science. We then propose an effective progression of upgrades based on technical feasibility and scientific scenarios