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

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

Electronic excitation of carbonyl sulphide (COS) by high-resolution vacuum ultraviolet photoabsorption and electron-impact spectroscopy in the energy region from 4 to 11 eV

The electronic state spectroscopy of carbonyl sulphide, COS, has been investigated using high resolution vacuum ultraviolet photoabsorption spectroscopy and electron energy loss spectroscopy in the energy range of 4.0–10.8 eV. The spectrum reveals several new features not previously reported in the literature. Vibronic structure has been observed, notably in the low energy absorption dipole forbidden band assigned to the (4π←3π) (1Δ←1Σ+) transition, with a new weak transition assigned to (1Σ−←1Σ+) reported here for the first time. The absolute optical oscillator strengths are determined for ground state to 1Σ+ and 1Π transitions. Based on our recent measurements of differential cross sections for the optically allowed (1Σ+ and 1Π) transitions of COS by electron impact, the optical oscillator strength f0 value and integral cross sections (ICSs) are derived by applying a generalized oscillator strength analysis. Subsequently, ICSs predicted by the scaling are confirmed down to 60 eV in the intermediate energy region. The measured absolute photoabsorption cross sections have been used to calculate the photolysis lifetime of carbonyl sulphide in the upper stratosphere (20–50 km)

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

Two 1993 Kamchatka earthquakes

Two earthquakes occurred in 1993 off southern Kamchatka. They have similar surface wave magnitudes, focal mechanisms, and depths, but have distinctly different characteristics. The November earthquake is a standard or “impulsive” M7 underthrusting event. The June earthquake is a tsunamigenic or “low-stress-drop” event with several unusual characteristics, including a large, diffuse aftershock zone, directivity, and a long source time function. The 1993 earthquakes ruptured a segment of the Kamchatka Arc which has not ruptured since 1904. The 1993 earthquakes seem to signal the midpoint in the southern Kamchatka seismic cycle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43211/1/24_2004_Article_BF00874387.pd