Analysis of a two-stage, flexible production system with unreliable machines, finite buffers and non-negligible setups

We analyze a Markov model of a two-stage production system capable of producing two part types. Each stage consists of an unreliable machine and the different stages are decoupled by two intermediate buffers of finite capacity, one for each part type. Unlike previous work, we specifically consider non-negligible machine setup times during changeovers and also assume that machine failure probabilities are dependent on the part type being produced. We assume that machine processing times, repair/failure times and setup times are exponentially distributed and may have different mean rates for each machine and for each part-type. We describe a solution method to evaluate the system performance that reduces the total number of equations to be solved from a multiplicative function to an additive function of buffer sizes. This model may then be integrated with a new decomposition method for analyzing longer lines. The results show the relative influence of different factors on system performance and thus provide guidance to the optimal choice of system parameters such as buffer sizes.     

Stochastic programming approach to process flexibility design

Service and manufacturing firms often attempt to mitigate demand-supply mismatch risks by deploying flexible resources that can be adapted to serve multiple demand classes. It is critical to evaluate the trade-off between the cost of investing in such resources and the resulting benefits. In this paper, we show that the heavily advocated “chaining” heuristic can sometimes perform unsatisfactorily when resources are not perfectly flexible. Alternatively, we propose an integer stochastic programming formulation as an attempt to optimize the flexibility structure. Although it is intractable to compute the optimal solution exactly, we propose a Lagrangian-relaxation heuristic that generates high-quality solutions efficiently. Using computational experiments, we identify conditions under which our approach can outperform the popular chaining solution.     

Decomposition methods for scheduling semiconductor testing facilities

We present decomposition procedures for scheduling semiconductor testing facilities. These facilities are characterized by the presence of different types of work centers, some of which have sequence-dependent setup times and some parallel identical machines. We exploit the structure of the routings in semiconductor testing to develop tailored decomposition procedures that decompose the shop into a number of work centers that are scheduled using specialized procedures. Extensive computational experiments show that these procedures significantly outperform existing methods in reasonable CPU times. These results indicate that decomposition methods can be successfully applied to complex scheduling problems of the type addressed in this paper, as well as the classical job shop problems addressed in previous research.     

Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes

The E. coli pyruvate and 2-oxoglutarate dehydrogenases are two closely related, large complexes that exemplify a growing number of multiprotein "machines" whose domains have been studied extensively and modeled in atomic detail, but whose quaternary structures have remained unclear for lack of an effective imaging technology. Here, electron cryotomography was used to show that the E1 and E3 subunits of these complexes are flexibly tethered approximately 11 nm away from the E2 core. This result demonstrates unambiguously that electron cryotomography can reveal the relative positions of features as small as 80 kDa in individual complexes, elucidating quaternary structure and conformational flexibility.     

The optimal configuration and workload allocation problem in flexible manufacturing systems

In this article we consider the problem of determining the minimum cost configuration (number of machines and pallets) for a flexible manufacturing system with the constraint of meeting a prespecified throughput, while simultaneously allocating the total workload among the machines (or groups of machines). Our procedure allows consideration of upper and lower bounds on the workload at each machine group. These bounds arise as a consequence of precedence constraints among the various operations and/or limitations on the number or combinations of operations that can be assigned to a machine because of constraints on tool slots or the space required to store assembly components. Earlier work on problems of this nature assumes that the workload allocation is given. For the single-machine-type problem we develop an efficient implicit enumeration procedure that uses fathoming rules to eliminate dominated configurations, and we present computational results. We discuss how this procedure can be used as a building block in solving the problem with multiple machine types.     

A novel flexible model for lot sizing and scheduling with non-triangular,period overlapping and carryover setups in different machine configurations

This paper develops and tests an efficient mixed integer programming model for capacitated lot sizing and scheduling with non-triangular and sequence-dependent setup times and costs incorporating all necessary features of setup carryover and overlapping on different machine configurations. The model’s formulation is based on the asymmetric travelling salesman problem and allows multiple lots of a product within a period. The model conserves the setup state when no product is being processed over successive periods, allows starting a setup in a period and ending it in the next period, permits ending a setup in a period and starting production in the next period(s), and enforces a minimum lot size over multiple periods. This new comprehensive model thus relaxes all limitations of physical separation between the periods. The model is first developed for a single machine and then extended to other machine configurations, including parallel machines and flexible flow lines. Computational tests demonstrate the flexibility and comprehensiveness of the proposed models.     

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.     

Process flexibility and inventory flexibility via product substitution

This paper studies the optimal control of and interaction between two types of flexibility under Markov models of demand and production: process flexibility and inventory flexibility. In our model, process flexibility is generated by a multi-functional production facility that can produce two types of products, and inventory flexibility is manifested in firm-driven one-way product substitution. Both process flexibility and inventory flexibility are important drivers of supply chain performance and are strategic design considerations. To analyze the interaction between these two types of flexibility, we model a dynamically controlled two-product, make-to-stock system with stochastic processing times and stochastic demand. We characterize the complex joint optimal production and post-production policy for a special case and numerically show that a simply structured multi-threshold policy is a near-optimal heuristic policy for the general case. We gain further insight into the impact of system parameters on the value of process flexibility and inventory flexibility via a comprehensive numerical study. We find that for a wide range of capacity and cost parameters, process flexibility and inventory flexibility complement each other, so pursuing both forms of flexibility is effective.     

Picking ChIP-seq peak detectors for analyzing chromatin modification experiments

Numerous algorithms have been developed to analyze ChIP-Seq data. However, the complexity of analyzing diverse patterns of ChIP-Seq signals, especially for epigenetic marks, still calls for the development of new algorithms and objective comparisons of existing methods. We developed Qeseq, an algorithm to detect regions of increased ChIP read density relative to background. Qeseq employs critical novel elements, such as iterative recalibration and neighbor joining of reads to identify enriched regions of any length. To objectively assess its performance relative to other 14 ChIP-Seq peak finders, we designed a novel protocol based on Validation Discriminant Analysis (VDA) to optimally select validation sites and generated two validation datasets, which are the most comprehensive to date for algorithmic benchmarking of key epigenetic marks. In addition, we systematically explored a total of 315 diverse parameter configurations from these algorithms and found that typically optimal parameters in one dataset do not generalize to other datasets. Nevertheless, default parameters show the most stable performance, suggesting that they should be used. This study also provides a reproducible and generalizable methodology for unbiased comparative analysis of high-throughput sequencing tools that can facilitate future algorithmic development.     

Grouping PCBs with Minimum Feeder Changes

In printed circuit board (PCB) assembly, the majority of electronic components are inserted by high-speed placement machines. Although the efficient utilization of the machinery is important for a manufacturer, it is hard to fully realize in high-mix low-volume production environments. On the machine level, the component setup strategy adopted by the manufacturer has a significant impact on the overall production efficiency. Usually, the setup strategy is formulated as a part type grouping problem or a minimum setup problem. In this article, we consider a hybridization of these two problems for the single machine case: The object function to be minimized includes a weighted sum of the number of part type groups (giving the number of setup occasions) and the number of feeder changeovers. We present algorithms for the problem and compare their efficiency.     

The ptychoid defensive mechanism in Euphthiracaroidea (Acari: Oribatida): A comparison of muscular elements with functional considerations

Ptychoidy is a mechanical predator defence in some groups of Oribatida (Acari), where the animals can retract their legs into the idiosoma and encapsulate. This mechanism is enabled by a number of morphological adaptations. We used the non-invasive technique of synchrotron X-ray microtomography to compare muscular elements involved in ptychoidy of two species from the Euphthiracaroidea (Oribotritia banksi and Rhysotritia ardua) which differ in a number of cuticular elements involved in ptychoidy. We hypothesize that a strong functional correlation exists between these cuticular structures and their corresponding musculature. We found a number of distinct differences concerning quantitative and qualitative muscle morphology. For testing the functional impact of different muscle configurations we simulated two conditions in silico (encapsulated / opened) and analysed the spatial relative force vectors of the prodorsum lateral adjustor muscles (pla) which are responsible for retraction and adjustment of the prodorsum during encapsulation. We show that the functional morphology of these muscles strongly differs between the two species and that this can be explained by the structure of corresponding cuticular elements. Furthermore, the dynamics of pla, as measured by the extent of contraction during encapsulation, is more than two times higher in R. ardua than in O. banksi.     

Using iRT, a normalized retention time for more targeted measurement of peptides

Multiple reaction monitoring (MRM) has recently become the method of choice for targeted quantitative measurement of proteins using mass spectrometry. The method, however, is limited in the number of peptides that can be measured in one run. This number can be markedly increased by scheduling the acquisition if the accurate retention time (RT) of each peptide is known. Here we present iRT, an empirically derived dimensionless peptide-specific value that allows for highly accurate RT prediction. The iRT of a peptide is a fixed number relative to a standard set of reference iRT-peptides that can be transferred across laboratories and chromatographic systems. We show that iRT facilitates the setup of multiplexed experiments with acquisition windows more than four times smaller compared to in silico RT predictions resulting in improved quantification accuracy. iRTs can be determined by any laboratory and shared transparently. The iRT concept has been implemented in Skyline, the most widely used software for MRM experiments.     

A Comparison Between Machine Flexibility and Routing Flexibility

In this paper, we evaluate two types of flexibility, machine flexibility and routing flexibility, in terms of manufacturing performance in various shop environments. A simulation-based investigation was conducted to analyze the impact of these types of flexibility on the average flow time of parts under various job flow pattern conditions, which characterize the shop nature from a random job shop to a flow shop, operation time variance, setup time, and shop load. The experimental results show how these types of flexibility affect the average flow time of parts and which type is superior under what conditions. Management can obtain better insight and guidelines for determining priorities or the scale, or scope, of various decision items relating to design standardization, process and operations improvement, investment in new equipment and tools, and the like.     

A comparative analysis of dynamic grids vs. virtual grids using the A3pviGrid framework

With the proliferation of Quad/Multi-core micro-processors in mainstream platforms such as desktops and workstations; a large number of unused CPU cycles can be utilized for running virtual machines (VMs) as dynamic nodes in distributed environments. Grid services and its service oriented business broker now termed cloud computing could deploy image based virtualization platforms enabling agent based resource management and dynamic fault management. In this paper we present an efficient way of utilizing heterogeneous virtual machines on idle desktops as an environment for consumption of high performance grid services. Spurious and exponential increases in the size of the datasets are constant concerns in medical and pharmaceutical industries due to the constant discovery and publication of large sequence databases. Traditional algorithms are not modeled at handing large data sizes under sudden and dynamic changes in the execution environment as previously discussed. This research was undertaken to compare our previous results with running the same test dataset with that of a virtual Grid platform using virtual machines (Virtualization). The implemented architecture, A3pviGrid utilizes game theoretic optimization and agent based team formation (Coalition) algorithms to improve upon scalability with respect to team formation. Due to the dynamic nature of distributed systems (as discussed in our previous work) all interactions were made local within a team transparently. This paper is a proof of concept of an experimental mini-Grid test-bed compared to running the platform on local virtual machines on a local test cluster. This was done to give every agent its own execution platform enabling anonymity and better control of the dynamic environmental parameters. We also analyze performance and scalability of Blast in a multiple virtual node setup and present our findings. This paper is an extension of our previous research on improving the BLAST application framework using dynamic Grids on virtualization platforms such as the virtual box.     

Economics and success factors of flexible manufacturing systems: The conventional explanation revisited

This article analyzes costs and relative benefits of several hundred flexible manufacturing systems (FMSs) in the world. The analyses are based on the computerized data bases, which make it easy to correlate different cost and benefit indicators with each other and to look for regular patterns and tendencies in the applications. Both investment cost distributions and the system complexity distributions are analyzed. The relative benefits and advantages and their relationships are shown. Finally, technical and economic explanations for successful implementation strategies are given. The results show that there are two classes of economically successful systems. The small-scale and technically compact systems are usually used in small-batch production for the replacement of semimanual production. The main benefits are increased capacity and productivity as well as quality improvements. The large-scale and technically complex systems are used in large-volume production for the replacement of fixed automation and transfer lines. The benefits are mainly due to the increased potential for flexibility and capital savings.     

Stochastic theory of early viral infection: continuous versus burst production of virions

Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production.     

Audio-Visual Detection Benefits in the Rat

Human psychophysical studies have described multisensory perceptual benefits such as enhanced detection rates and faster reaction times in great detail. However, the neural circuits and mechanism underlying multisensory integration remain difficult to study in the primate brain. While rodents offer the advantage of a range of experimental methodologies to study the neural basis of multisensory processing, rodent studies are still limited due to the small number of available multisensory protocols. We here demonstrate the feasibility of an audio-visual stimulus detection task for rats, in which the animals detect lateralized uni- and multi-sensory stimuli in a two-response forced choice paradigm. We show that animals reliably learn and perform this task. Reaction times were significantly faster and behavioral performance levels higher in multisensory compared to unisensory conditions. This benefit was strongest for dim visual targets, in agreement with classical patterns of multisensory integration, and was specific to task-informative sounds, while uninformative sounds speeded reaction times with little costs for detection performance. Importantly, multisensory benefits for stimulus detection and reaction times appeared at different levels of task proficiency and training experience, suggesting distinct mechanisms inducing these two multisensory benefits. Our results demonstrate behavioral multisensory enhancement in rats in analogy to behavioral patterns known from other species, such as humans. In addition, our paradigm enriches the set of behavioral tasks on which future studies can rely, for example to combine behavioral measurements with imaging or pharmacological studies in the behaving animal or to study changes of integration properties in disease models.     

The flexibility of DNA double crossover molecules

Double crossover molecules are DNA structures containing two Holliday junctions connected by two double helical arms. There are several types of double crossover molecules, differentiated by the relative orientations of their helix axes, parallel or antiparallel, and by the number of double helical half-turns (even or odd) between the two crossovers. They are found as intermediates in meiosis and they have been used extensively in structural DNA nanotechnology for the construction of one-dimensional and two-dimensional arrays and in a DNA nanomechanical device. Whereas the parallel double helical molecules are usually not well behaved, we have focused on the antiparallel molecules; antiparallel molecules with an even number of half-turns between crossovers (termed DAE molecules) produce a reporter strand when ligated, facilitating their characterization in a ligation cyclization assay. Hence, we have estimated the flexibility of antiparallel DNA double crossover molecules by means of ligation-closure experiments. We are able to show that these molecules are approximately twice as rigid as linear duplex DNA.     

Oligo(dT) is not a correct native PAGE marker for single-stranded DNA

Polyacrylamide gel electrophoresis is a widely used method to study short DNA fragments in solution. It is, however, a relative method requiring length markers to assess mobility, shape, flexibility, and molecularity of the DNA structures of interest. In recent literature we have encountered the use of oligo(dT) fragments as the native PAGE length markers. We show here that this practice is inadequate because oligo(dT) migration is strongly retarded in native polyacrylamide gels. This conclusion is qualitatively true irrespective of the conditions of electrophoresis, oligo(dT) length, and gel concentration. Depending on their length, oligo(dT) fragments migrate 2--4 times slower than that would correspond to their nucleotide number. This leads to erroneous conclusions, e.g., determination of the number of associated molecules in guanine quadruplexes or other DNA complexes.