Multicellular Tumor Spheroids (MCTS) as a 3D In Vitro Evaluation Tool of Nanoparticles

Multicellular tumor spheroid models (MCTS) are often coined as 3D in vitro models that can mimic the microenvironment of tissues. MCTS have gained increasing interest in the nano‐biotechnology field as they can provide easily accessible information on the performance of nanoparticles without using animal models. Considering that many countries have put restrictions on animals testing, which will only tighten in the future as seen by the recent developments in the Netherlands, 3D models will become an even more valuable tool. Here, an overview on MCTS is provided, focusing on their use in cancer research as most nanoparticles are tested in MCTS for treatment of primary tumors. Thereafter, various types of nanoparticles—from self‐assembled block copolymers to inorganic nanoparticles, are discussed. A range of physicochemical parameters including the size, shape, surface chemistry, ligands attachment, stability, and stiffness are found to influence nanoparticles in MCTS. Some of these studies are complemented by animal studies confirming that lessons from MCTS can in part predict the behaviour in vivo. In summary, MCTS are suitable models to gain additional information on nanoparticles. While not being able to replace in vivo studies, they can bridge the gap between traditional 2D in vitro studies and in vivo models.     

Influence of particle contact models on soil response of poorly graded sand during cavity expansion in discrete element simulation

The discrete element method (DEM) has been extensively adopted to investigate many complex geotechnical related problems due to its capability to incorporate the discontinuous nature of granular materials. In particular, when simulating large deformations or distortion of soil (e.g. cavity expansion), DEM can be very effective as other numerical solutions may experience convergence problems. Cavity expansion theory has widespread applications in geotechnical engineering, particularly to the problems concerning in situ testing, pile installation and so forth. In addition, the behaviour of geomaterials in a macro-level is utterly determined by microscopic properties, highlighting the importance of contact models. Despite the fact that there are numerous contact models proposed to mimic the realistic behaviour of granular materials, there are lack of studies on the effects of these contact models on the soil response. Hence, in this study, a series of three-dimensional numerical simulations with different contact constitutive models was conducted to simulate the response of sandy soils during cylindrical cavity expansion. In this numerical investigation, three contact models, i.e. linear contact model, rolling resistance contact model, and Hertz contact model, are considered. It should be noted that the former two models are linear based models, providing linearly elastic and frictional plasticity behaviours, whereas the latter one consists of nonlinear formulation based on an approximation of the theory of Mindlin and Deresiewicz. To examine the effects of these contact models, several cylindrical cavities were created and expanded gradually from an initial radius of 0.055 m to a final radius of 0.1 m. The numerical predictions confirm that the calibrated contact models produced similar results regarding the variations of cavity pressure, radial stress, deviatoric stress, volumetric strain, as well as the soil radial displacement. However, the linear contact model may result in inaccurate predictions when highly angular soil particles are involved. In addition, considering the excessive soil displacement induced by the pile installation (i.e. cavity expansion), a minimum distance of 11a (a is the cavity radius) is recommend for practicing engineers to avoid the potential damages to the existing piles and adjacent structures.     

Tissue-Specific Ferritin- and GFP-Based Genetic Vectors Visualize Neurons by MRI in the Intact and Post-Ischemic Rat Brain

(1) Background: Neurogenesis is considered to be a potential brain repair mechanism and is enhanced in stroke. It is difficult to reconstruct the neurogenesis process only from the histological sections taken from different animals at different stages of brain damage and restoration. Study of neurogenesis would greatly benefit from development of tissue-specific visualization probes. (2) Purpose: The study aimed to explore if overexpression of ferritin, a nontoxic iron-binding protein, under a doublecortin promoter can be used for non-invasive visualization of neurogenesis using magnetic resonance imaging (MRI). (3) Methods: Ferritin heavy chain (FerrH) was expressed in the adeno-associated viral backbone (AAV) under the doublecortin promoter (pDCX), specific for young neurons, in the viral construct AAV-pDCX-FerrH. Expression of the enhanced green fluorescent protein (eGFP) was used as an expression control (AAV-pDCX-eGFP). The viral vectors or phosphate-buffered saline (PBS) were injected intracerebrally into 18 adult male Sprague–Dawley rats. Three days before injection, rats underwent transient middle-cerebral-artery occlusion or sham operation. Animals were subjected to In vivo MRI study before surgery and on days 7, 14, 21, and 28 days after injection using a Bruker BioSpec 11.7 T scanner. Brain sections obtained on day 28 after injection were immunostained for ferritin, young (DCX) and mature (NeuN) neurons, and activated microglia/macrophages (CD68). Additionally, RT-PCR was performed to confirm ferritin expression. (4) Results: T2* images in post-ischemic brains of animals injected with AAV-pDCX-FerrH showed two distinct zones of MRI signal hypointensity in the ipsilesioned hemisphere starting from 14 days after viral injection—in the ischemic lesion and near the lateral ventricle and subventricular zone (SVZ). In sham-operated animals, only one zone of hypointensity near the lateral ventricle and SVZ was revealed. Immunochemistry showed that ferritin-expressing cells in ischemic lesions were macrophages (88.1%), while ferritin-expressing cells near the lateral ventricle in animals both after ischemia and sham operation were mostly mature (55.7% and 61.8%, respectively) and young (30.6% and 7.1%, respectively) neurons. RT-PCR confirmed upregulated expression of ferritin in the caudoputamen and corpus callosum. Surprisingly, in animals injected with AAV-pDCX-eGFP we similarly observed two zones of hypointensity on T2* images. Cellular studies also showed the presence of mature (81.5%) and young neurons (6.1%) near the lateral ventricle in both postischemic and sham-operated animals, while macrophages in ischemic lesions were ferritin-positive (98.2%). (5) Conclusion: Ferritin overexpression induced by injection of AAV-pDCX-FerrH was detected by MRI using T2*-weighted images, which was confirmed by immunochemistry showing ferritin in young and mature neurons. Expression of eGFP also caused a comparable reduced MR signal intensity in T2*-weighted images. Additional studies are needed to investigate the potential and tissue-specific features of the use of eGFP and ferritin expression in MRI studies.     

微间隙共形圆柱接触力模型的适用性分析

针对目前间隙铰接副接触力模型无法有效表述不同材料耗散阻尼效应,以及不适用于微间隙共形接触的问题,分析各种接触力模型中弹性接触力和耗散阻尼力计算方法的优缺点,提出一种普适性的圆柱内接触力分析模型。该模型将接触力描述为接触深度的显式函数,并将其适用范围有效地扩展至微间隙和低恢复系数工况。采用含间隙铰接副的曲柄-滑块机构进行动力学分析,对所提出接触力进行验证,计算结果表明:所提出的普适性接触力模型体现了微间隙时更高的接触刚度和低恢复系数时显著的阻尼效应,从而可为不同材料和间隙尺寸的间隙铰接副力学分析提供更为完备的计算模型。     

大数据在公共卫生应急管理中的应用--以内蒙古自治区为例

在此次新冠肺炎防控中,以大数据为代表的新一代信息技术,广泛应用于疫情管控、追踪溯源、模型预测、资源调配、舆情管控等多个方面,发挥了重大作用。通过对大数据在内蒙古自治区疫情防控中的应用分析,从应用情况、存在问题及对策建议三个方面,探讨如何合理有效地利用丰富的数据资源、大数据应用技术,对完善重大疫情防控体制机制提供强有力的支撑,从而推动自治区,乃至国家公共卫生应急管理体系的健全与完善。     

Effects of Sparger Holes on Gas-Liquid Hydrodynamics in Bubble Columns

A multiphase second-order moment turbulent model was developed including an improved closure Reynolds stress transport to describe effectively the anisotropic characteristics of bubble-liquid turbulent flow. The two-phase hydrodynamics in a bubble column were numerically simulated by an in-house code. The effect of the amount of jetting holes on bubble-liquid hydrodynamics in relationship with a cell culture was investigated. Firstly, the bubble energy production correlation was proposed to verify the higher cell damage rate near gas inlet regions. The larger amounts of jetting holes resulted in an increase of bubble stress, bubble kinetic energy, and energy dissipation, particularly bubble energy production at the near gas inlet, which boosted cell damage.     

Nonlinear Factor-Augmented Predictive Regression Models with Functional Coefficients

This article introduces a new class of functional-coefficient predictive regression models, where the regressors consist of auto-regressors and latent factor regressors, and the coefficients vary with certain index variable. The unobservable factor regressors are estimated through imposing an approximate factor model on high dimensional exogenous variables and subsequently implementing the classical principal component analysis. With the estimated factor regressors, a local linear smoothing method is used to estimate the coefficient functions (with appropriate rotation) and obtain a one-step ahead nonlinear forecast of the response variable, and then a wild bootstrap procedure is introduced to construct the prediction interval. Under regularity conditions, the asymptotic properties of the proposed methods are derived, showing that the local linear estimator and the nonlinear forecast using the estimated factor regressors are asymptotically equivalent to those using the true latent factor regressors. The developed model and methodology are further generalized to the factor-augmented vector predictive regression with functional coefficients. Finally, some extensive simulation studies and an empirical application to forecast the UK inflation are given to examine the finite-sample performance of the proposed model and methodology.     

What’s the middle ground? Institutionalized vs. emerging water-related stakeholder engagement processes

Abstract

In this day and age, it is widely argued that stakeholder engagement in water-related decision-making processes yields many benefits, including legitimacy, acceptance and trust. Key legal frameworks, such as the European Water Framework Directive and the Aarhus Convention, have spurred the emergence of formal forms of stakeholder engagement. On the other hand, many engagement processes are spontaneous and self-organized. This article investigates the strategies used in formal (government-led) and informal (bottom-up) engagement processes in search of a middle ground. To this end, case studies in the Netherlands, the United States, Uganda and Ethiopia are analyzed using the OECD’s stakeholder engagement checklist. We conclude with reflection on the ways forward to make formal and informal stakeholder engagement complementary.