Abstract. We present microphysical observations of cumulus clouds measured over the southwest peninsula of the UK during the COnvective Precipitation Experiment (COPE) in August 2013, which are framed into a wider context using ground-based and airborne radar measurements. Two lines of cumulus clouds formed in the early afternoon along convergence lines aligned with the peninsula. The lines became longer and broader during the afternoon due to new cell formation and stratiform regions forming downwind of the convective cells. Ice concentrations up to 350 L −1 , well in excess of the expected ice nuclei (IN) concentrations, were measured in the mature stratiform regions, suggesting that secondary ice production was active.Detailed sampling focused on an isolated liquid cloud that glaciated as it matured to merge with a band of cloud downwind. In the initial cell, drizzle concentrations increased from ∼ 0.5 to ∼ 20 L −1 in around 20 min. Ice concentrations developed up to a few per litre, which is around the level expected of primary IN. The ice images were most consistent with freezing drizzle, rather than smaller cloud drops or interstitial IN forming the first ice.As new cells emerged in and around the cloud, ice concentrations up to 2 orders of magnitude higher than the predicted IN concentrations developed, and the cloud glaciated over a period of 12-15 min. Almost all of the first ice particles to be observed were frozen drops, while vapour-grown ice crystals were dominant in the latter stages. Our observations are consistent with the production of large numbers of small secondary ice crystals/fragments, by a mechanism such as Hallett-Mossop or droplets shattering upon freezing. Some of the small ice froze drizzle drops on contact, while others grew more slowly by vapour deposition. Graupel and columns were seen in cloud penetrations up to the −12 • C level, though many ice particles were mixed habit due to riming and growth by vapour deposition at multiple temperatures.Our observations demonstrate that the freezing of drizzle/raindrops is an important process that dominates the formation of large ice in the intermediate stages of cloud development. As these frozen drops were the first precipitation observed, interactions between the warm-rain and secondary ice production processes appear to be key to determining the timing and location of precipitation.

Background Gastric cancer (GC) is a common cancer in Asia and currently lacks a targeted therapy approach. Mesothelin (MSLN) has been reported to be expressed in GC tissue and could be targeted by chimeric antigen receptor (CAR) T cells. Mesothelin targeting CAR-T has been reported in mesothelioma, lung cancer, breast cancer, and pancreas cancer. However, the feasibility of using anti-MSLN CAR T cells to treat GC remains to be studied. Methods We verified MSLN expression in primary human GC tissues and GC cell lines and then redirected T cells with a CAR containing the MSLN scFv (single-chain variable fragment), CD3ζ, CD28, and DAP10 intracellular signaling domain (M28z10) to target MSLN. We evaluated the function of these CAR T cells in vitro in terms of cytotoxicity, cytokine secretion, and surface phenotype changes when they encountered MSLN+ GC cells. We also established four different xenograft GC mouse models to assess in vivo antitumor activity. Results M28z10 T cells exhibited strong cytotoxicity and cytokine-secreting ability against GC cells in vitro. In addition, cell surface phenotyping suggested significant activation of M28z10 T cells upon target cell stimulation. M28z10 T cells induced GC regression in different xenograft mouse models and prolonged the survival of these mice compared with GFP-transduced T cells in the intraperitoneal and pulmonary metastatic GC models. Importantly, peritumoral delivery strategy can lead to improved CAR-T cells infiltration into tumor tissue and significantly suppress the growth of GC in a subcutaneous GC model. Conclusion These results demonstrate that M28z10 T cells possess strong antitumor activity and represent a promising therapeutic approach to GC.

Purpose: The study aimed to investigate the association between body composition and frailty in elder inpatients. Patients and Methods: This is a cross-sectional study including 656 elder inpatients (275 females and 381 males) aged ≥65 years, from department of geriatrics of Zhejiang Hospital between January 2018 and March 2019. Sociodemographic, health-related data and anthropometric measurements were evaluated. Body composition was assessed by bioimpedance analysis (BIA), mainly including skeletal muscle mass, body fat mass, total body water, fat-free mass,percent body fat, basal metabolic rate. Frailty was assessed by Clinical Frailty Scale (CFS). Univariate logistic regression was used to analyze the association between body composition and frailty. Results: Frailty was present in 43.9% of the participants. Frail inpatients showed higher waist circumference, body fat mass and percent body fat, non-frail inpatients showed greater upper arm circumference, calf circumference, skeletal muscle mass, total body water, fat-free mass and basal metabolic rate. Subjects with underweight (body mass index (BMI)<18.5 kg/m 2 ; odds ratio (OR), 95% confidence interval (CI)=4.146 (1.286-13.368) P=0.017) and those with high waist circumference (OR 95% CI=1.428 (0.584-3.491) P<0.001), body fat mass (OR, 95% CI=1.143 (0.892-1.315) P<0.001) presented a higher risk of frailty compared to normal subjects. Skeletal muscle mass (OR; 95% CI=0.159 (0.064-0.396) P<0.001) was a protective factor for frailty. Conclusion: Frailty in elder Chinese inpatients was characterized by a body composition phenotype with underweight, high waist circumference, low skeletal muscle mass and high body fat mass. Underweight, abdominal obesity and sarcopenic obesity may, therefore, be targets for intervention of frailty.

BackgroundThe mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult.MethodsIn this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT).ResultsMice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg−/− (NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays.ConclusionsThe TEI score was effectively able to reflect the immunodeficiency of a mouse strain.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0156-y) contains supplementary material, which is available to authorized users.