Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

膨胀剂对约束条件下UHPC早期抗裂性能影响的试验研究

超高性能混凝土(UHPC)在钢桥面铺装结构中由于铺装材料受到钢板、栓钉等的约束,加上材料本身水胶比小,更易收缩,早期容易承受拉应力导致开裂。通过在拌和过程中添加膨胀剂可以起到减小收缩的作用,但该方法对于约束条件下的UHPC铺装的早期抗裂性能提升是否有促进作用,仍需通过更多试验进行合理评估和深入研究。通过圆环法对3组不同配方的UHPC在均匀约束条件下的早期抗裂性能进行定量测试,并将试验数据进行回归分析和计算,得到了各组的平均应力发展速率,进而评估了各组的开裂风险等级。试验结果表明,通过在UHPC中加入适量膨胀剂,可使其最终收缩应力减小,并可降低其收缩应力发展速率,进一步降低其在约束条件下的开裂风险。     

张峰水库溢洪道体型优化设计

本文对已设计的张峰水库溢洪道进行了模型试验,根据对试验结果分析,认为原方案设计存在一些问题,并针对问题进行了优化设计。通过对修改方案模型试验结果分析,得出修改方案改进了原方案中存在的不足,优化合理,是可以采用的。     

Model Selection for Unsupervised Learning of Visual Context

This study addresses the problem of choosing the most suitable probabilistic model selection criterion for unsupervised learning of visual context of a dynamic scene using mixture models. A rectified Bayesian Information Criterion (BICr) and a Completed Likelihood Akaike’s Information Criterion (CL-AIC) are formulated to estimate the optimal model order (complexity) for a given visual scene. Both criteria are designed to overcome poor model selection by existing popular criteria when the data sample size varies from small to large and the true mixture distribution kernel functions differ from the assumed ones. Extensive experiments on learning visual context for dynamic scene modelling are carried out to demonstrate the effectiveness of BICr and CL-AIC, compared to that of existing popular model selection criteria including BIC, AIC and Integrated Completed Likelihood (ICL). Our study suggests that for learning visual context using a mixture model, BICr is the most appropriate criterion given sparse data, while CL-AIC should be chosen given moderate or large data sample sizes.     

The factorial structure of the Dutch translation of the Inventory of Interpersonal Problems: A test of the long and short versions.

In this article, the authors study the factorial structure of 2 versions (64 items and 32 items) of the Dutch translation of the Inventory of Interpersonal Problems (IIP; L. M. Horowitz, L. E. Alden, J. S. Wiggins, & A. L. Pincus, 2000) in both a clinical sample (n = 382) and a student sample (n = 287). First, the authors test whether both inventories are constituted by correlated uni-dimensional subscales, and they conclude that this is true only for the short version. Second, the authors study whether the correlations between the subscales follow a circumplex pattern. This proves to be true for both versions. Coefficients alpha and correlations between the IIP-64 and IIP-32 subscales are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

重力坝模型的尺寸效应

利用两个不同比尺预制缝重力坝模型的试验成果，以有限元富集技术进行非线性断裂分析，建立了极限承载力和长度比尺的确定性尺寸效应公式。混凝土重力坝的断裂尺寸效应满足指数衰减关系，用三次指数衰减公式可以准确地预测原型的极限承载力。断裂过程区的相对长度是引起模型试验尺寸效应的主要原因。数值计算结果表明，断裂过程区相对长度不仅是与材料有关的参数，能否充分发展还取决于结构尺寸和几何形状；断裂过程区相对长度的尺寸效应不同于统计尺寸效应和断裂参数尺寸效应，具有尺寸范围效应。断裂过程区相对长度在小试件、大试件和相对无穷大试件的发展程度不同。     

PETROLEUM MIGRATION, FAULTS AND OVERPRESSURE, PART I: CALIBRATING BASIN MODELLING USING PETROLEUM IN TRAPS — A REVIEW

This paper considers the principles of deciphering basin-scale hydrocarbon migration patterns using the geochemical information which is present in trapped petroleum. Petroleum accumulations in subsiding basins can be thought of as "data archives" within which stored information can help us to understand aspects of hydrocarbon formation and migration. This information can impart a time-resolved picture of hydrocarbon migration in a basin in response to processes associated with progressive burial, particularly in the context of the occurrence and periodic activity of faults.
This review, which includes a series of tentative models of migration-related processes in the extensional Halten Terrace area, offshore mid-Norway, illustrates how we can use information from the migrating mobile hydrocarbon phase to improve our knowledge of the static geological system. Of particular importance is the role of sub-seismic heterogeneities and faults in controlling migration processes. We focus on how the secondary migration process can be enhanced in a multi-source rock basin such as the Halten Terrace, thereby increasing prospectivity.     

对空监视雷达探测威力检飞的几个问题

以新的观点论证了对空监视雷达探测威力检验飞行中所需的采样点数和飞行架次，讨论了预警机雷达威力检飞的特殊问题，包括地区选择、航线设计和目标机标定等。