Improved cascade control structure for enhanced performance

In conventional single feedback control, the corrective action for disturbances does not begin until the controlled variable deviates from the set point. In this case, a cascade control strategy can be used to improve the performance of a control system particularly in the presence of disturbances. In this paper, an improved cascade control structure and controller design based on standard forms, which was initially given by authors, is suggested to improve the performance of cascade control. Examples are given to illustrate the use of the proposed method and its superiority over some existing design methods

IL-13-induced airway mucus production is attenuated by MAPK13 inhibition

Increased mucus production is a common cause of morbidity and mortality in inflammatory airway diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. However, the precise molecular mechanisms for pathogenic mucus production are largely undetermined. Accordingly, there are no specific and effective anti-mucus therapeutics. Here, we define a signaling pathway from chloride channel calcium-activated 1 (CLCA1) to MAPK13 that is responsible for IL-13–driven mucus production in human airway epithelial cells. The same pathway was also highly activated in the lungs of humans with excess mucus production due to COPD. We further validated the pathway by using structure-based drug design to develop a series of novel MAPK13 inhibitors with nanomolar potency that effectively reduced mucus production in human airway epithelial cells. These results uncover and validate a new pathway for regulating mucus production as well as a corresponding therapeutic approach to mucus overproduction in inflammatory airway diseases

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Virtues of Consistency

I found the PID2006 special section in the February 2006 issue quite interesting. When analog computers were used for control, the subject of time scaling was often discussed. This technique, now little mentioned, is useful for examining the consistency of PID tuning rules

Control engineering and the analog computer: academic and industrial machines in Britain

This paper provides a brief historical review of analog computing and its role in control engineering, particularly in the British academic and industrial setting. It includes a discussion on commercial analog computer developments and the university requirements for analog computers

Some reflections on analogue simulation and control engineering

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Textbooks and Classical Controller Design

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Limit Cycles in Nonlinear Systems with Fractional Order Plants

In recent years, there has been considerable interest in the study of feedback systems containing processes whose dynamics are best described by fractional order derivatives. Various situations have been cited for describing heat flow and aspects of bioengineering, where such models are believed to be superior. In many situations these feedback systems are not linear and information on their stability and the possibility of the existence of limit cycles is required. This paper presents new results for determining limit cycles using the approximate describing function method and an exact method when the nonlinearity is a relay characteristic

State feedback design to obtain standard form responses

The paper presents a procedure for designing state feedback controllers to achieve a standard form closed loop system step response. Apart from addressing directly the step response in the design it also allows consideration of time scaling and control signal magnitude, important aspects not often considered in other approaches. The method can be used for a forward loop transfer function with one or no zero. Thus if a PI controller is used the plant transfer function must have no zero

Basic Nonlinear Control Systems

This section is written to introduce the reader to nonlinearity and its effect in control systems, and also to 'set the stage' for the subsequent articles. Nonlinearity is first defined and then some of the physical effects which cause nonlinear behaviour are discussed. This is followed by some comments on the stability of nonlinear systems, the existence of limit cycles, and the unique behavioral aspects which nonlinear feedback systems may possess. Finally a few brief comments are made on designing controllers for nonlinear systems