On modeling the design of cellular manufacturing systems

A new optimization model is discussed for the design of cellular manufacturing systems. It is based on an integer programming formulation that updates some other models by eliminating redundant machine assignment and cost coefficients dependent on cell configuration. To reduce computational burdens, a simplified integer programming model and a decomposition algorithm are proposed. Several computer solutions were performed to evaluate the performance of the new model. The computational results are discussed.     

Variations in novel cellular therapy products manufacturing

Background aimsAt the frontier of transfusion medicine and transplantation, the field of cellular therapy is emerging. Most novel cellular therapy products are produced under investigational protocols with no clear standardization across cell processing centers. Thus, the purpose of this study was to uncover any variations in manufacturing practices for similar cellular therapy products across different cell processing laboratories worldwide.MethodsAn exploratory survey that was designed to identify variations in manufacturing practices in novel cellular therapy products was sent to cell processing laboratory directors worldwide. The questionnaire focused on the manufacturing life cycle of different cell therapies (i.e., collection, purification, in vitro expansion, freezing and storage, and thawing and washing), as well as the level of regulations followed to process each product type.ResultsThe majority of the centers processed hematopoietic progenitor cells (HPCs) from peripheral blood (n = 18), bone marrow (n = 16) or cord blood (n = 19), making HPCs the most commonly processed cells. The next most commonly produced cellular therapies were lymphocytes (n = 19) followed by mesenchymal stromal cells (n = 14), dendritic cells (n = 9) and natural killer (NK) cells (n = 9). A minority of centers (<5) processed pancreatic islet cells (n = 4), neural cells (n = 3) and induced-pluripotent stem cells (n = 3). Thirty-two laboratories processed products under an investigational status, for either phase I/II (n = 27) or phase III (n = 17) clinical trials. If purification methods were used, these varied for the type of product processed and by institution. Environmental monitoring methods also varied by product type and institution.ConclusionThis exploratory survey shows a wide variation in cellular therapy manufacturing practices across different cell processing laboratories. A better understanding of the effect of these variations on the quality of these cell-based therapies will be important to assess for further process evaluation and development.     

Detection of 2-hydroxyethidium in cellular systems: a unique marker product of superoxide and hydroethidine

Various detection methods of the specific product of reaction of superoxide (O(2)(*-)) with hydroethidine (HE), namely 2-hydroxyethidium (2-OH-E(+)), and with its mitochondria-targeted analog are described. The detailed protocol for quantification of 2-OH-E(+), the unique product of HE/O(2)(*-) in cellular systems, is presented. The procedure includes cell lysis, protein precipitation using acidified methanol and HPLC analysis of the lysate. Using this protocol, we determined the intracellular levels of 2-OH-E(+) and E(+) in the range of 10 and 100 pmol per mg protein in unstimulated macrophage-like RAW 264.7 cells. In addition to HE, 2-OH-E(+) and E(+), we detected several dimeric products of HE oxidation in cell lysates. As several oxidation products of HE are formed, the superoxide-specific product, 2-OH-E(+) needs to be separated from other HE-derived products for unequivocal quantification.     

Performance management in flexible manufacturing systems

This article treats several performance management decision problems in flexible manufacturing systems (FMSs). This work differs from a number of other studies in that we allow the processing rates at the machines to be varied, and the system has to meet a given throughput goal per unit time. The managerial decision options modeled here include part routing and allocation of tasks to machines, work-in-progress (WIP) levels, capacity expansions, tool-type selection, the setting of throughput goals, and multiperiod production planning. We discuss and explain the insights and implications, partly nonintuitive, gained from our investigations. Finally, extensive numerical evaluations are included to illustrate the economic and performance impact of the various performance management alternatives. These results demonstrate that substantial economic benefits can be achieved by careful tuning of the FMS operational parameters.     

The measurement of flexibility in manufacturing systems

This article provides a theoretical basis for measuring the flexibility of manufacturing systems. The concept of multiple levels of measures (necessary, capability, actual, inflexibility, and optimality) for each flexibility type is introduced. Capability and actual measures are then developed for machine, routing, process, product, and volume flexibilities. For each of these flexibility types, a state defining variable is identified. A measure of flexibility is then derived by computing either, (i) the change effort expended in moving between states, (ii) the drop in system performance in moving between states, (iii) a general or physical scale of difference between two successive states, or (iv) a measure combining all three. The use of the developed measures is illustrated via a two-facility example.     

Effects of lanthanum in cellular systems

Lanthanum belongs to the group of elements known as “lanthanons,” which also includes cerium, europium, promethium, and thulium. It is the most electropositive element of the rare earth group, is uniformly trivalent, and is similar in its chemical properties to the alkaline earth elements. The effects of this element and its compounds on cellular systems are of considerable interest because of their increasing use in industry and as a substitute or antagonist for calcium in a variety of cellular reactions. Lanthanum is also being employed extensively in studying anatomical barriers, membrane structure, and subcellular transport systems, particularly the calcium pathway.     

Rule-based production planning in flexible manufacturing systems

Production planning in flexible manufacturing may require the solution of a large-scale discrete-event dynamic stochastic optimization problem, due to the complexity of the system to be optimized, and to the occurrence of discrete events (new orders and hard failures). The production planning problem is here approached for a multistage multipart-type manufacturing shop, where each work cell can share its processing time among the different types of parts. The solution of this problem is obtained by an open-loop-feedback control strategy, updated each time a new event occurs. At each event time, two coupled problems are solved: 1) a product-order scheduling problem, conditioned on estimated values of the production capacities of all component work cells; and 2) a production-capacity planning problem, conditioned on predefined sequences of the product orders to be processed. In particular, the article aims at defining a production planning procedure that integrates both analytical tools, derived from mathematical programming, and knowledge-based rules, coming from experience. The objective is to formulate a hybrid (knowledge-based/analytical) planning architecture, and to analyze its use for multicell multipart-type manufacturing systems.     

Reliability analysis of flexible manufacturing systems

High productivity is the primary goal of flexible manufacturing systems (FMSs) in which semi-independent workstations are integrated using automated material-transport systems and hierarchical local networks. Availability of various subsystems and of the system as a whole is a prerequisite for achieving functional integration as well as high throughput. An FMS also has inherent routing and operation flexibilities that provide it with a certain degree of fault tolerance. A certain volume of production can thus be maintained in the face of subsystem (i.e., machines, robots, material handling system, etc.) failures. In this article, we propose two reliability measures, namely, part reliability (PR) and FMS reliability (FMSR) for manufacturing systems and present algorithms to evaluate them. We also consider the dynamic or time-dependent reliability analysis as a natural generalization of the static analysis. The methods outlined use an algorithm that generates process-spanning graphs (PSGs), which are used to evaluate the reliability measures.     

Bio-inspired self-organizing cellular systems

Bio-inspiration borrows three properties characteristic of living organisms: multicellular architecture, cellular division, and cellular differentiation. Implemented in silicon according to these properties, our self-organizing systems are able to grow, to self-replicate, and to self-repair. The growth and branching processes, performed by the so-called Tom Thumb algorithm, lead thus to the configuration and cloning mechanisms of the systems. The repair processes allow its cicatrization and regeneration mechanisms. The cellular design and hardware implementation of these mechanisms constitute the core of this paper.     

Positive feedback in cellular control systems

Feedback loops have been identified in a variety of regulatory systems and organisms. While feedback loops of the same type (negative or positive) tend to have properties in common, they can play distinctively diverse roles in different regulatory systems, where they can affect virulence in a pathogenic bacterium, maturation patterns of vertebrate oocytes and transitions through cell cycle phases in eukaryotic cells. This review focuses on the properties and functions of positive feedback in biological systems, including bistability, hysteresis and activation surges.     

A model management systems approach to manufacturing systems design

Manufacturing systems design involves the solution of a complex series of interrelated problems. This complexity will increase in the future as manufacturing practices change to meet increased global competition. Research within manufacturing systems design has mainly been focused on finding improved models for solving particular problems, or extending existing modeling techniques. This has resulted in numerous modeling tools being available to support manufacturing systems design. However, little research work has been carried out into consolidating the existing theories and models. As a result, a large body of this work has not been applied in industry. Model management has evolved as a research area which investigates methods for storing, modifying, and manipulating models. This article describes a prototype model management system for manufacturing systems design. The objective here is not to develop “another” decision support system for manufacturing design, but to illustrate, through the development of a prototype system, a number of key ideas of how concepts from the area of model management systems can be used to support manufacturing systems design. The prototype model management system utilizes the structured modeling framework and uses an extended version of the structured modeling language. An important aspect of the prototype model management system is the incorporation of the model development task, thus allowing the system to be easily updated and adapted. The prototype system was evaluated using a range of queueing network models for manufacturing systems design.     

Evolutionarily stable mixed mating in a variety of genetic systems

Many species display a mixture of close inbreeding and outbreeding which is referred to as mixed mating. For selfing species, models predict that such mixed mating systems can be stable. Conversely, models considering separate sex species have not been able to explain mixed mating systems. This failure may be a result of the unrealistic assumption that recurrent inbreeding does not increase the inbreeding coefficient. Here we show that mixed mating is expected in separate sex systems when recurrent inbreeding is taken into account. A female that allows her brother to sibmate with her gives an extra mating opportunity to said brother. This kin selective advantage should be strongest in genetic systems where the male is more related to the female. In support of this idea, we find that inbreeding evolves most easily in selfers, followed by diploid sibmating, followed by haplodiploid sibmating. Consideration of published values for the regression of fitness on inbreeding coefficient suggests that many species fall in a range where some selfing/sibmating is optimal.     

Modeling customized product configuration in large assembly manufacturing with supply-chain considerations

Dynamic variability in low-volume and highly customized products of a large assembly manufacturing system with an integrated supply chain has been very challenging to capture. Design and product configurations most likely impact outcomes of such broad variability. This article presents a framework to encompass this completely integrated system for using discrete event simulation as a modeling method. The system modeling framework addresses factors including customized configuration attributes and individual customer-preferred considerations for customized configurations. The framework is intended to aid decision-making concerning cost and schedule impacts associated with customization options chosen throughout the supply chain. A real-world example drawn from aerospace is included to demonstrate and validate the operational capability of the proposed framework.     

Flexible and reconfigurable manufacturing systems paradigms

Reconfigurable Manufacturing System (RMS) is a new manufacturing systems paradigm that aims at achieving cost-effective and rapid system changes, as needed and when needed, by incorporating principles of modularity, integrability, flexibility, scalability, convertibility, and diagnosability. RMS promises customized flexibility on demand in a short time, while Flexible Manufacturing Systems (FMSs) provides generalized flexibility designed for the anticipated variations and built-in a priori. The characteristics of the two paradigms are outlined and compared. The concept of manufacturing system life cycle is presented. The main types of flexibility in manufacturing systems are discussed and contrasted with the various reconfiguration aspects including hard (physical) and soft (logical) reconfiguration. The types of changeability and transformability of manufacturing systems, their components as well as factories, are presented along with their enablers and compared with flexibility and reconfigurability. The importance of having harmonized human-machine manufacturing systems is highlighted and the role of people in the various manufacturing paradigms and how this varies in pursuit of productivity are illustrated. Finally, the industrial and research challenges presented by these manufacturing paradigms are discussed.     

Evaluating the design of flexible manufacturing systems

Evaluating the design of flexible manufacturing systems is complex. Developing a measure of performance useful for evaluating alternate designs continues to be interesting. Here, total productivity of the system is proposed as an appropriate measure. Specification of parameters based upon strategic considerations for this measure are discussed. Finally, the usefulness of the measure is demonstrated through an example.