Information flow through a model of the C. elegans klinotaxis circuit

Understanding how information about external stimuli is transformed into behavior is one of the central goals of neuroscience. Here we characterize the information flow through a complete sensorimotor circuit: from stimulus, to sensory neurons, to interneurons, to motor neurons, to muscles, to motion. Specifically, we apply a recently developed framework for quantifying information flow to a previously published ensemble of models of salt klinotaxis in the nematode worm C. elegans. The models are grounded in the neuroanatomy and currently known neurophysiology of the worm. The unknown model parameters were optimized to reproduce the worm's behavior. Information flow analysis reveals several key principles underlying how the models operate: (1) Interneuron class AIY is responsible for integrating information about positive and negative changes in concentration, and exhibits a strong left/right information asymmetry. (2) Gap junctions play a crucial role in the transfer of information responsible for the information symmetry observed in interneuron class AIZ. (3) Neck motor neuron class SMB implements an information gating mechanism that underlies the circuit's state-dependent response. (4) The neck carries non-uniform distribution about changes in concentration. Thus, not all directions of movement are equally informative. Each of these findings corresponds to an experimental prediction that could be tested in the worm to greatly refine our understanding of the neural circuit underlying klinotaxis. Information flow analysis also allows us to explore how information flow relates to underlying electrophysiology. Despite large variations in the neural parameters of individual circuits, the overall information flow architecture circuit is remarkably consistent across the ensemble, suggesting that information flow analysis captures general principles of operation for the klinotaxis circuit

Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press

Context: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release. Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets. Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured. Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for tablet weight but significantly affect volume of powder inside the feeder in case of powders with excellent flowability (DCP). The opposite effect of paddle speed was observed for fairly flowing powders (MCC). Tableting speed played a role in weight and weight variability, whereas changing fill depth exclusively influenced tablet weight. Conclusion: The DoE approach allowed predicting the optimum combination of process parameters leading to minimum tablet weight variability. Monte Carlo simulations allowed assessing the probability to exceed the acceptable response limits if factor settings were varied around their optimum. This multi-dimensional combination and interaction of input variables leading to response criteria with acceptable probability reflected the design space

Process monitoring and visualization solutions for hot-melt extrusion : a review

Objectives: Hot-melt extrusion (HME) is applied as a continuous pharmaceutical manufacturing process for the production of a variety of dosage forms and formulations. To ensure the continuity of this process, the quality of the extrudates must be assessed continuously during manufacturing. The objective of this review is to provide an overview and evaluation of the available process analytical techniques which can be applied in hot-melt extrusion. Key Findings: Pharmaceutical extruders are equipped with traditional (univariate) process monitoring tools, observing barrel and die temperatures, throughput, screw speed, torque, drive amperage, melt pressure and melt temperature. The relevance of several spectroscopic process analytical techniques for monitoring and control of pharmaceutical HME has been explored recently. Nevertheless, many other sensors visualizing HME and measuring diverse critical product and process parameters with potential use in pharmaceutical extrusion are available, and were thoroughly studied in polymer extrusion. The implementation of process analytical tools in HME serves two purposes: (1) improving process understanding by monitoring and visualizing the material behaviour and (2) monitoring and analysing critical product and process parameters for process control, allowing to maintain a desired process state and guaranteeing the quality of the end product. Summary: This review is the first to provide an evaluation of the process analytical tools applied for pharmaceutical HME monitoring and control, and discusses techniques that have been used in polymer extrusion having potential for monitoring and control of pharmaceutical HME

Sticking together or falling apart? Solidarity in an era of individualization and globalization

"This book examines, both theoretically and empirically, the impact of globalization and individualization on social solidarity. It focuses both on informal solidarity, such as volunteering, charitable giving, and informal care, and on formal solidarity, such as social benefits and development aid. It challenges the common belief that social solidarity is endangered by the increasing competition and capital flows between countries and by growing selfishness of modern citizens. The book scrutinizes the theoretical arguments that both informal solidarity and social solidarity organized through the welfare state are eroding. Empirically, it is the first thorough study of international comparative data on solidarity, globalization and individualization. The book concludes that, overall, solidarity is rising rather than declining. The impact of globalization and individualization is much more ambiguous than is often contended. While particular aspects of globalization and individualization might harm solidarity, other elements foster solidarity instead." [author's abstract]Dit boek onderzoekt in theoretisch en empirisch opzicht welke gevolgen globalisering en individualisering hebben voor solidariteit. Het besteedt aandacht aan informele solidariteit, zoals vrijwilligerswerk en mantelzorg, en aan formele solidariteit, zoals sociale uitkeringen en ontwikkelingshulp. Het plaatst kanttekeningen bij het wijd verbreide geloof dat de groeiende internationale concurrentie en kapitaalstromen en het toenemende egocentrisme van moderne burgers de solidariteit ondergraven