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.
The Convective Precipitation Experiment (COPE) was a joint U.K.–U.S. field campaign held during the summer of 2013 in the southwest peninsula of England, designed to study convective clouds that produce heavy rain leading to flash floods. The clouds form along convergence lines that develop regularly as a result of the topography. Major flash floods have occurred in the past, most famously at Boscastle in 2004. It has been suggested that much of the rain was produced by warm rain processes, similar to some flash floods that have occurred in the United States. The overarching goal of COPE is to improve quantitative convective precipitation forecasting by understanding the interactions of the cloud microphysics and dynamics and thereby to improve numerical weather prediction (NWP) model skill for forecasts of flash floods. Two research aircraft, the University of Wyoming King Air and the U.K. BAe 146, obtained detailed in situ and remote sensing measurements in, around, and below storms on several days. A new fast-scanning X-band dual-polarization Doppler radar made 360° volume scans over 10 elevation angles approximately every 5 min and was augmented by two Met Office C-band radars and the Chilbolton S-band radar. Detailed aerosol measurements were made on the aircraft and on the ground. This paper i) provides an overview of the COPE field campaign and the resulting dataset, ii) presents examples of heavy convective rainfall in clouds containing ice and also in relatively shallow clouds through the warm rain process alone, and iii) explains how COPE data will be used to improve high-resolution NWP models for operational use.
Background: Chimeric antigen receptor T cells (CAR-T cells) therapy has been well recognized for treating B cellderived malignancy. However, the efficacy of CART cells against solid tumors remains dissatisfactory, partially due to the heterogeneity of solid tumors and T cell exhaustion in tumor microenvironment. PD-L1 is up-regulated in multiple solid tumors, resulting in T cell exhaustion upon binding to its receptor PD-1. Methods: Here, we designed a dominant-negative form of PD-1, dPD1z, a vector containing the extracellular and transmembrane regions of human PD-1, and a CAR vector against PD-L1, CARPD-L1z, a vector employs a highaffinity single-chain variable fragment (scFv) against human PD-L1. These two vectors shared the same intracellular structure, including 4-1BB and TLR2 co-stimulatory domains, and the CD3ζ signaling domain. Results: dPD1z T and CARPD-L1z T cells efficiently lysed PD-L1 + tumor cells and had enhanced cytokine secretion in vitro and suppressed the growth of non-small cell lung cancer (NSCLC), gastric cancer and hepatoma carcinoma in patient-derived xenograft (PDX). However, the combination of anti-mesothelin CART cells (CARMSLNz T) with dPD1z T or CARPD-L1z T cells did not repress tumor growth synergistically in PDX, as CARMSLNz T cells upregulated PD-L1 expression upon activation and were subsequently attacked by dPD1z T or CARPD-L1z T cells. Conclusions: In conclusion, we demonstrate CART cells targeting PD-L1 were effective for suppressing the growth of multiple types of solid tumors in PDX models though their safety needs to be carefully examined.
Despite being impactful on a variety of problems and applications, the generative adversarial nets (GANs) are remarkably difficult to train. This issue is formally analyzed by , who also propose an alternative direction to avoid the caveats in the minmax two-player training of GANs. The corresponding algorithm, called Wasserstein GAN (WGAN), hinges on the 1-Lipschitz continuity of the discriminator. In this paper, we propose a novel approach to enforcing the Lipschitz continuity in the training procedure of WGANs. Our approach seamlessly connects WGAN with one of the recent semi-supervised learning methods. As a result, it gives rise to not only better photo-realistic samples than the previous methods but also state-of-the-art semi-supervised learning results. In particular, our approach gives rise to the inception score of more than 5.0 with only 1,000 CIFAR-10 images and is the first that exceeds the accuracy of 90% on the CIFAR-10 dataset using only 4,000 labeled images, to the best of our knowledge.
1. Global variation in litter decomposition rates is driven by climate, decomposer taxa and litter quality. Most large-scale studies of litter quality have made comparisons across species, rather than within a species sourced from different latitudes.Here, we aim to explore latitudinal variation in leaf litter decomposition rate and litter quality within a species.2. We investigated whether the typical interspecific pattern of increased litter lability at higher latitudes also holds within plant species, by comparing leaf litter decomposition rates and litter traits from stands of native Phragmites australis and exotic Spartina alterniflora in Chinese coastal wetlands spanning 20° of latitude using parallel greenhouse and field transplant experiments.3. We found that leaf litter from high-latitude plants decomposed 46.6 ± 5.1% faster than that from low-latitude conspecifics, with similar patterns in both plant species in both decomposition experiments. Higher lability of leaves from high latitudes was associated with lower levels of plant defensive compounds (phenolics and tannins) and higher levels of nutrients (Ca, Mg and Na). Litter from the exotic S. alterniflora decomposed faster than litter from the native P. australis, being consistent with lower defences and higher nutrient concentrations in S. alterniflora litter. 4. Our results show that individual species follow the same pattern of increasing litter lability at higher latitudes previously reported in cross-species geographical comparisons. Moreover, this pattern can develop rapidly (<4 decades) in an introduced species, raising the question of whether it is caused by phenotypic plasticity or adaptation.
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