Secondary proton flux induced by cosmic ray interactions with the atmosphere

The atmospheric secondary proton flux is studied for altitudes extending from sea level up to the top of atmosphere by means of a 3-dimensional Monte-Carlo simulation procedure successfully used previously to account for flux measurements of protons, light nuclei, and electrons-positrons below the geomagnetic cutoff (satellite data), and of muons and antiprotons (balloon data). The calculated flux are compared with the experimental measurements from sea level uo to high float ballon altitudes. The agreement between data and simulation results are very good at all altitudes, including the lowest ones, where the calculations become extremely sensitive to the proton production cross section. The results are discussed in this context. The calculations are extended to the study of quasi trapped particles above the atmosphere to about 5 Earth radii, for prospective purpose.Comment: 7 pages, 5 figures, submitted to Phys. Rev.

Upconverting nanoparticles: A versatile platform for wide-field two-photon microscopy and multi-modal in vivo imaging

Lanthanide-doped upconverting nanoparticles (UCNPs) have recently attracted enormous attention in the field of biological imaging owing to their unique optical properties: (1) efficient upconversion photoluminescence, which is intense enough to be detected at the single-particle level with a (nonscanning) wide-field microscope setup equipped with a continuous wave (CW) near-infrared (NIR) laser (980 nm), and (2) resistance to photoblinking and photobleaching. Moreover, the use of NIR excitation minimizes adverse photoinduced effects such as cellular photodamage and the autofluorescence background. Finally, the cytotoxicity of UCNPs is much lower than that of other nanoparticle systems. All these advantages can be exploited simultaneously without any conflicts, which enables the establishment of a novel UCNP-based platform for wide-field two-photon microscopy. UCNPs are also useful for multimodal in vivo imaging because simple variations in the composition of the lattice atoms and dopant ions integrated into the particles can be easily implemented, yielding various distinct biomedical activities relevant to magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). These multiple functions embedded in a single type of UCNPs play a crucial role in precise disease diagnosis. The application of UCNPs is extended to therapeutic fields such as photodynamic and photothermal cancer therapies through advanced surface conjugation schemes. This journal is © The Royal Society of Chemistry12092361sciescopu

Association of TIM-3 checkpoint receptor expression on T cells with treatment-free remission in chronic myeloid leukemia

Dysregulation of immune checkpoint receptors has been reported at diagnosis of chronic myeloid leukemia (CML), but their role in the maintenance of remission after tyrosine kinase inhibitor (TKI) cessation is unclear. We assessed PD-1, TIM-3, CTLA-4, LAG-3 and TIGIT expression on T-cell subsets, regulatory T cells (T-regs), and natural killer (NK) cells at the time of TKI cessation in 44 patients (22 who sustained treatment-free remission (TFR), 22 who experienced molecular relapse (MolR)). We confirmed our previous finding that absolute numbers of T-regs are increased in MolR patients compared to TFR. The immune checkpoint receptors PD-1, CTLA-4, LAG-3 and TIGIT on T or NK cells were not differentially expressed between the MolR and TFR groups. However, TIM-3 was consistently upregulated on bulk T-cells (CD3+), and T-cell subsets including, CD4+T-cells, CD8+T-cells, and T-regs, in patients who relapsed in comparison to those who maintained TFR after discontinuation. Furthermore, gene expression analysis from publicly available datasets showed increased TIM-3 expression on CML stem cells compared with normal hematopoietic stem cells. These findings suggest that among the targetable immune checkpoint molecules, TIM-3 blockade may potentially improve effector immune response in CML patients stopping TKI, whilst concomitantly targeting leukemic stem cells, and could be a promising therapeutic strategy for preventing relapse after cessation of TKI in CML patients.Yazad D. Irani, Chung H. Kok, Jade Clarson, Naranie Shanmuganathan, Susan Branford, David T. Yeung, David M. Ross, Timothy P. Hughes and Agnes S. M. Yon

Successful treatment-free remission in chronic myeloid leukaemia and its association with reduced immune suppressors and increased natural killer cells

There is currently no biomarker that reliably predicts treatment-free remission (TFR) in chronic myeloid leukaemia (CML). We characterised effector and suppressor immune responses at the time of tyrosine kinase inhibitor (TKI) cessation in patients from the CML8 and CML10 clinical studies. Natural killer (NK) cells with increased expression of activating NK receptors were higher in patients who achieved TFR. There was no difference in the proportion of CD4+ or CD8+ T cells. Furthermore, we found that FoxP3+ regulatory T cells (T reg) and monocytic myeloid-derived suppressor cells (Mo-MDSCs) were concomitantly decreased in TFR patients, suggesting that the effector and suppressor arms of the immune system work in concert to mediate TFR. A discovery cohort (CML10) was used to generate a predictive model, using logistic regression. Patients classified into the high-risk group were more likely to relapse when compared with the low-risk group (HR 7·4, 95% CI 2·9-19·1). The model was successfully validated on the independent CML8 cohort (HR 8·3, 95% CI 2·2-31·3). Effective prediction of TFR success may be obtained with an effector-suppressor score, calculated using absolute NK cell, T reg, and Mo-MDSC counts, at TKI cessation, reflecting the contribution of both immune suppressors and effectors in the immunobiology underlying successful TFR.Yazad D. Irani, Amy Hughes, Jade Clarson, Chung H. Kok, Naranie Shanmuganathan, Deborah L. White, David T. Yeung, David M. Ross, Timothy P. Hughes, and Agnes S.M. Yon

Optimisation of ultrasonic-assisted hot-water extraction conditions of soluble dietary fibre from Lentinula edodes and analysis of its hypolipidaemic and anti-inflammatory properties in STZ-induced diabetic mice

Soluble dietary fibre (SDF) is well recognised for its remarkable effectiveness in promoting human health. This study utilised response surface methodology to evaluate the optimal conditions required to extract SDF (U-SDF) from Lentinula edodes via the ultrasonic-assisted hot-water method, and evaluated the hypolipidemic effects and anti-inflammatory effects of U-SDF. The optimal extraction conditions for U-SDF were ultrasonic power of 182 W, extraction time of 2 h, extraction temperature of 81 °C, and solid-liquid ratio of 1:24 (g mL −1 ). Under these conditions, the extraction rate of U-SDF reached 8.08%. U-SDF treatment significantly improved liver and kidney indices in diabetic mice, markedly reduced the levels of plasma triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and significantly increased the level of high-density lipoprotein-cholesterol (HDL-C) in a dose-dependent manner. U-SDF also improved adipose tissue injury in diabetic mice, significantly decreased the levels of cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α), and alleviated inflammation of the abdominal aorta. In conclusion, U-SDF from L. edodes is an excellent source of dietary fibres, which exhibit good hypolipidemic and anti-inflammatory activities, suggesting potential applications as a functional additive in diverse food products

Peptide-based bimetallic nanostructures with tailored surface compositions and their oxygen electroreduction activities

We report the synthesis of surface-composition-controlled gold-platinum (AuPt) bimetallic nanostructures on carbon nanotubes by peptide-based self-assembly and their catalytic responses to oxygen reduction. Our results can provide a great opportunity to construct various nanostructures with tailored properties. © 2016 The Royal Society of Chemistry7