Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real‐time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid‐to‐solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGma^TM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2500–2514, 2018     

Automated manufacturability analysis: A survey

In the market-place of the 21st century, there is no place for traditional over-the-wall communications between design and manufacturing. In order to design it right the very first time, designers must ensure that their products are both functional and easy to manufacture. Software tools have had some successes in reducing the barriers between design and manufacturing. Manufacturability analysis systems are emerging as one such tool — enabling identification of potential manufacturing problems during the design phase and providing suggestions to designers on how to eliminate them.In this paper, we provide a survey of current state-of-the-art automated manufacturability analysis. We present the historical context in which this area has emerged and outline characteristics to compare and classify various systems. We describe the two dominant approaches to automated manufacturability analysis and overview representative systems based on their application domain. We describe support tools that enhance the effectiveness of manufacturability analysis systems. Finally, we attempt to expose some of the existing research challenges and future directions.     

Addressing Particle Compositional Heterogeneities in Super-Resolution-Enhanced Live-Cell Ratiometric pH Sensing with Ultrasmall Fluorescent Core–Shell Aluminosilicate Nanoparticles

The interrogation of metabolic parameters like pH in live-cell experiments using optical super-resolution microscopy (SRM) remains challenging. This is due to a paucity of appropriate metabolic probes enabling live-cell SRM-based sensing. Here, ultrasmall fluorescent core–shell aluminosilicate nanoparticle sensors (FAM–ATTO647N aC′ dots) that covalently encapsulate a reference dye (ATTO647N) in the core and a pH-sensing moiety (FAM) in the shell are introduced. Only the reference dye exhibits optical blinking enabling live-cell stochastic optical reconstruction microscopy (STORM). Using data from cells incubated for 60 min with FAM–ATTO647N aC′ dots, pixelated information from total internal reflection fluorescence (TIRF) microscopy-based ratiometric sensing can be combined with that from STORM-based localizations via the blinking reference dye in order to enhance the resolution of ratiometric pH sensor maps beyond the optical diffraction limit. A nearest-neighbor interpolation methodology is developed to quantitatively address particle compositional heterogeneity as determined by separate single-particle fluorescence imaging methods. When combined with STORM-based estimates of the number of particles per vesicle, vesicle size, and vesicular motion as a whole, this analysis provides detailed live-cell spatial and functional information, paving the way to a comprehensive mapping and understanding of the spatiotemporal evolution of nanoparticle processing by cells important, e.g., for applications in nanomedicine.     

Bi‐Layered Tubular Microfiber Scaffolds as Functional Templates for Engineering Human Intestinal Smooth Muscle Tissue

Designing biomimetic scaffolds with in vivo–like microenvironments using biomaterials is an essential component of successful tissue engineering approaches. The intestinal smooth muscle layers exhibit a complex tubular structure consisting of two concentric muscle layers in which the inner circular layer is orthogonally oriented to the outer longitudinal layer. Here, a 3D bi‐layered tubular scaffold is presented based on flexible, mechanically robust, and well aligned silk protein microfibers to mimic the native human intestinal smooth muscle structure. The scaffolds are seeded with primary human intestinal smooth muscle cells to replicate intestinal muscle tissues in vitro. Characterization of the tissue constructs reveals good biocompatibility and support for cell alignment and elongation in the different scaffold layers to enhance cell differentiation and functions. Furthermore, the engineered smooth muscle constructs support oriented neurite outgrowth, a requisite step to achieve functional innervation. These results suggest these microfiber scaffolds as functional templates for in vitro regeneration of human intestinal smooth muscle systems. The scaffolding provides a crucial step toward engineering functional human intestinal tissue in vitro, as well as engineering other types of smooth muscles in terms of their similar phenotypes. Such utility may lead to a better understanding of smooth muscle associated diseases and treatments.     

Formalising the Hybrid ERTMS Level 3 specification in iUML-B and Event-B

We demonstrate refinement-based formal development of the hybrid, ‘fixed virtual block’ approach to train movement control for the emerging European Rail Traffic Management System (ERTMS) level 3. Our approach uses iUML-B diagrams as a front end to the Event-B modelling language. We use abstraction to verify the principle of movement authority before gradually developing the details of the Virtual Block Detector component in subsequent refinements, thus verifying that it preserves the safety properties. We animate the refined models to demonstrate their validity using the scenarios from the Hybrid ERTMS Level 3 (HLIII) specification. We reflect on our team-based approach to finding useful modelling abstractions and demonstrate a systematic modelling method based on the state and class diagrams of iUML-B. The component and control flow architectures of the application, its environment and interacting systems emerge through the layered refinement process. The runtime semantics of the specification’s state-machine behaviour are modelled in the final refinements. We discuss how the model could be used to generate an implementation using code generation tools and techniques.

     

Water Denitration over a Pd–Sn/Al2O3 Catalyst

Bimetallic Pd–Sn catalysts were synthesized by incipient-wetness impregnation of the metals on alumina and employed for the reduction of nitrates from aqueous solutions. The catalysts were characterized by FTIR spectroscopy of adsorbed CO, X-ray diffraction (XRD), transmission electron microscopy (TEM), and H₂ chemisorption. The influence of the metal ratio was evaluated in reaction measurements. The bimetallic Pd–Sn catalysts exhibited high selectivity for nitrate removal forming less NO₂⁻ and NH₄⁺ than the Pd–Cu catalysts.     

非重叠监控视频中基于颜色空间分布模型的行人匹配方法

针对非重叠视域监控系统中行人目标关联问题,提出了一种基于颜色空间分布模型的行人目标匹配方法。使用最邻近聚类方法对目标的像素进行聚类,得到目标的MC特征;建立目标的颜色空间分布模型,并进行特征转换;在建立的分布模型的基础上,计算目标相似度并进行匹配。实验结果表明,该算法能有效地去除目标检测与分割产生的边缘背景像素的影响,在对相同目标保持较高匹配率的情况下,能较好地处理由于目标颜色分布差异而造成的误匹配情况,同时对于摄像机视角的差异以及目标姿态的变化有较好的鲁棒性。     

Effect of Packing Pressures and Particle Size Variations on the Reaction Kinetics for PbTiO3 and PbZrO3 Formation

The rate constant for solid-state reactions for PbTiO₃ formation was increased by a factor of three by increasing the packing pressures. Similarly, rate constants for PbZrO₃ formation were shown to increase with decreasing ZrO₂ particle and crystallite sizes. Quantitative X-ray diffraction analyses were utilized to determine the extent of the reactions.