A loop layout design problem for flexible manufacturing systems

The interconnection pattern of the processing modules of a computerized manufacturing system affects its performance. In this article, we discuss a set of requirements that the interconnection network should satisfy. Subsequently, we concentrate on a simple and popular architecture, the loop network. The problem we address is to design the layout of the system so that the number of machines that the part types cross in their manufacturing process is minimized. We formulate the problem mathematically and solve it by a heuristic that obtains consistently better results than an earlier popular method.     

Automatic selection of partitioning schemes for phylogenetic analyses using iterative k-means clustering of site rates

Background

Model selection is a vital part of most phylogenetic analyses, and accounting for the heterogeneity in evolutionary patterns across sites is particularly important. Mixture models and partitioning are commonly used to account for this variation, and partitioning is the most popular approach. Most current partitioning methods require some a priori partitioning scheme to be defined, typically guided by known structural features of the sequences, such as gene boundaries or codon positions. Recent evidence suggests that these a priori boundaries often fail to adequately account for variation in rates and patterns of evolution among sites. Furthermore, new phylogenomic datasets such as those assembled from ultra-conserved elements lack obvious structural features on which to define a priori partitioning schemes. The upshot is that, for many phylogenetic datasets, partitioned models of molecular evolution may be inadequate, thus limiting the accuracy of downstream phylogenetic analyses.

Results

We present a new algorithm that automatically selects a partitioning scheme via the iterative division of the alignment into subsets of similar sites based on their rates of evolution. We compare this method to existing approaches using a wide range of empirical datasets, and show that it consistently leads to large increases in the fit of partitioned models of molecular evolution when measured using AICc and BIC scores. In doing so, we demonstrate that some related approaches to solving this problem may have been associated with a small but important bias.

Conclusions

Our method provides an alternative to traditional approaches to partitioning, such as dividing alignments by gene and codon position. Because our method is data-driven, it can be used to estimate partitioned models for all types of alignments, including those that are not amenable to traditional approaches to partitioning.     

Lujiatun Psittacosaurids: Understanding Individual and Taphonomic Variation Using 3D Geometric Morphometrics

Psittacosaurus is one of the most abundant and speciose genera in the Dinosauria, with fifteen named species. The genus is geographically and temporally widespread with large sample sizes of several of the nominal species allowing detailed analysis of intra- and interspecific variation. We present a reanalysis of three separate, coeval species within the Psittacosauridae; P. lujiatunensis, P. major, and Hongshanosaurus houi from the Lujiatun beds of the Yixian Formation, northeastern China, using three-dimensional geometric morphometrics on a sample set of thirty skulls in combination with a reevaluation of the proposed character states for each species. Using these complementary methods, we show that individual and taphonomic variation are the joint causes of a large range of variation among the skulls when they are plotted in a morphospace. Our results demonstrate that there is only one species of Psittacosaurus within the Lujiatun beds and that the three nominal species represent different taphomorphotypes of P. lujiatunensis. The wide range of geometric morphometric variation in a single species of Psittacosaurus implies that the range of variation found in other dinosaurian groups may also be related to taphonomic distortion rather than interspecific variation. As the morphospace is driven primarily by variation resulting from taphonomic distortion, this study demonstrates that the geometric morphometric approach can only be used with great caution to delineate interspecific variation in Psittacosaurus and likely other dinosaur groups without a complementary evaluation of character states. This study presents the first application of 3D geometric morphometrics to the dinosaurian morphospace and the first attempt to quantify taphonomic variation in dinosaur skulls.     

Modeling methodology for defining a priori the hydrodynamics of a dynamic suspension bioreactor. Application to human induced pluripotent stem cell culture

Three-dimensional dynamic suspension is becoming an effective cell culture method for a wide range of bioprocesses, with an increasing number of bioreactors proposed for this purpose. The complex hydrodynamics establishing within these devices affects bioprocess outcomes and efficiency, and usually expensive in vitro trial-and-error experiments are needed to properly set the working parameters.Here we propose a methodology to define a priori the hydrodynamic working parameters of a dynamic suspension bioreactor, selected as a test case because of the complex hydrodynamics characterizing its operating condition. A combination of computational and analytical approaches was applied to generate operational guideline graphs for defining a priori specific working parameters. In detail, 43 simulations were performed under pulsed flow regime to characterize advective transport within the device depending on different operative conditions, i.e., culture medium flow rate and its duty cycle, cultured particle diameter, and initial particle suspension volume. The operational guideline graphs were then used to set specific hydrodynamic working parameters for an in vitro proof-of-principle test, where human induced pluripotent stem cell (hiPSC) aggregates were cultured for 24 h within the bioreactor. The in vitro findings showed that, under the selected pulsed flow regime, sedimentation was avoided, hiPSC aggregate circularity and viability were preserved, and culture heterogeneity was reduced, thus confirming the appropriateness of the a priori method. This methodology has the potential to be adaptable to other dynamic suspension devices to support experimental studies by providing in silico-based a priori knowledge, useful to limit costs and to optimize culture bioprocesses.     

Production activity control: A practical approach to scheduling

There is a widely perceived gap within the domain of scheduling for manufacturing systems, namely, many of the methods employed by production supervisors are quite different from those developed by researchers. In a sense, this inconsistency highlights the important fact that much scheduling research has failed to win approval where it matters most, namely, within the manufacturing system. In this article, we argue for a practical approach to scheduling for manufacturing systems, one that we believe can narrow, and possibly bridge, the gap between theory and practice. This approach is based upon a well-defined and modular architecture for scheduling, termedproduction activity control. This architecture is the foundation of our proposed solution to scheduling, since it provides a coherent blueprint for the synthesis of information technology and scheduling strategies. The result of this synthesis is a design tool for production activity control, which allows for detailed and disciplined experimentation with a range of scheduling strategies in a controlled and simulated environment. Due to the unique modular property of the design tool, these strategies may then be implemented live in a flexible manufacturing facility, hence narrowing the gap between scheduling theory and manufacturing practice. Our overall approach is tested through an appropriate implementation in a modern electronics assembly plant.     

A scalable life cycle inventory of an automotive power electronic inverter unit—part II: manufacturing processes

Purpose

A scalable life cycle inventory (LCI) model, which provides mass composition and gate-to-gate manufacturing data for a power electronic inverter unit intended for controlling electric vehicle propulsion motors, was developed. The purpose is to fill existing data gaps for life cycle assessment (LCA) of electric vehicles. The model comprises new and easy-to-use data with sufficient level of detail to enable proper component scaling and in-depth analysis of inverter units. The aim of this article (part II) is to describe the modeling of all production steps and present new datasets. Another objective is to explain the strategies for data collection, system boundaries, and how unit process datasets were made to interact properly with the scalable design model (part I).

Methods

Data for the manufacturing of the inverter unit was collected from a variety of literature, technical specifications, factory data, site visits, and expert interviews. The model represents current levels of technology and modern industrial scale production. Industry data dates back to 2012. Some older literature is referred to, but only if it was found to remain relevant. Upstream, new data has been gathered to the point where the Ecoinvent database can be used to model a full cradle-to-gate inventory. To make the LCI model easy to use, each flow crossing the system boundary is reported with a recommended linked flow to this database.

Results and discussion

The screening and modeling of manufacturing inverter units resulted in a substantial compilation of new inventory data. In close integration with the design model, which is scalable in size over a range of 20–200 kW in nominal power and 250–700 V in DC system voltage (part I), it forms a comprehensive scalable LCI model of a typical automotive power electronic inverter unit intended for traction motor control. New production data covers electroplating of gold, electro-galvanization, machining and anodizing of aluminum, ceramic substrate fabrication, direct copper bonding, photoimaging and regenerative etching, power module assembly with a two-step soldering process, and the assembly of automotive printed circuit boards.

Conclusions

Interviews with experts were found to be vital for effective data collection and the reporting of details a key to maintaining data usability over time, for reuse, rework, and criticism by other LCA practitioners.

     

Application of Absorption Modeling to Predict Bioequivalence Outcome of Two Batches of Etoricoxib Tablets

As part of the overall product development and manufacturing strategy, pharmaceutical companies routinely change formulation and manufacturing site. Depending on the type and level of change and the BCS class of the molecule, dissolution data and/or bioequivalence (BE) may be needed to support the change for immediate release dosage forms. In this report, we demonstrate that for certain weakly basic low-solubility molecules which rapidly dissolve in the stomach, absorption modeling could be used to justify a BE study waiver even when there is failure to show dissolution similarity under some conditions. The development of an absorption model for etoricoxib is described here, which was then used to a priori predict the BE outcome of tablet batches manufactured at two sites. Dissolution studies in 0.01 N HCl media (pH 2.0) had demonstrated similarity of etoricoxib tablets manufactured at two different sites. However, dissolution testing at pH 4.5 and pH 6.8 media failed to show comparability of the tablets manufactured at the two sites. Single simulations and virtual trials conducted using the 0.01 N HCl dissolution showed similarity in AUC and C_max for all tablet strengths for batches manufactured at the two manufacturing sites. These predicted results were verified in a definitive bioequivalence study, which showed that both tablet batches were bioequivalent. Since the development of traditional in vitro–in vivo correlations (IVIVC) for immediate release (IR) products is challenging, in cases such as etoricoxib, absorption modeling could be used as an alternative to support waiver of a BE study.KEY WORDS: bioequivalence, dissolution, modeling, pharmacokinetics, SUPAC     

Tissue correlations in linear samples

A line sample is made through an aggregate of many tissue types. The question treated is whether the observed distribution of heterotype contacts is consistent with a random placement of the tissues. A generating function in the form of a weighted Markov chain is set up and analyzed for various assumptions as to a priori probabilities. The case in which all tissue types but the pair being assayed are combined in a communal tissue is solved explicitly in the limit of a large sample. Corrections due to finite sample size and to the detailed structure of the communal tissue are carried out.     

Workload balance and part-transfer minimization in flexible manufacturing systems

Problems related to the flow management of a flexible manufacturing system (FMS) are here formulated in terms of combinatorial optimization. We consider a system consisting of several multitool automated machines, each one equipped with a possibly different tool set and linked to each other by a transportation system for part moving. The system operates with a given production mix. The focused flow-management problem is that of finding the part routings allowing for an optimal machine workload balancing. The problem is formulated in terms of a particular capacity assignment problem. With the proposed approach, a balanced solution can be achieved by routing parts on a limited number of different paths. Such a balancing routing can be found in polynomial time. We also give polynomial-time and-space algorithms for choosing, among all workload-balancing routings, the ones that minimize the global amount of part transfer among all machines.     

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.     

Production Capacity Modeling of Alternative, Nonidentical, Flexible Machines

Analyzing the production capacity of a flexible manufacturing system consisting of a number of alternative, nonidentical, flexible machines, where each machine is capable of producing several different part types simultaneously (by flexibly allocating its production capacity among these part types), is not a trivial task. The production capacity set of such a system is naturally expressed in terms of the machine-specific production rates of all part types. In this paper we also express it in terms of the total production rates of all part types over all machines. More specifically, we express the capacity set as the convex hull of a set of points corresponding to all possible assignments of machines to part types, where in each assignment each machine allocates all its capacity to only one part type. First, we show that within each subset of assignments having a given number of machines assigned to each part type, there is a unique assignment that corresponds to an extreme point of the capacity set. Then, we propose a procedure for generating all the extreme points and facets of the capacity set. Numerical experience shows that when the number of part types is less than four, the size of the capacity set (measured in terms of the number of variables times the number of constraints) is smaller, if the capacity set is expressed in terms of the total production rates of all part types over all machines than if it is expressed in terms of the machine-specific production rates of all part types. When the number of part types is four or more, however, the opposite is true.     

On the identifiability of linear compartmental systems: a revisited transfer function approach based on topological properties

This work deals with the problem of the a priori identifiability of compartmental systems from input-output experiments. A new approach is presented, in which, having associated a directed graph with the matrix to be identified, a set of “forms” is defined which are functions of the elements of matrix itself. It is shown how, by exploiting the topological properties of the graph and its subgraphs, the problem can be simplified into one of smaller dimensions. Examples are provided to illustrate this new approach.     

On Simplified Global Nonlinear Function for Fitness Landscape: A Case Study of Inverse Protein Folding

The construction of fitness landscape has broad implication in understanding molecular evolution, cellular epigenetic state, and protein structures. We studied the problem of constructing fitness landscape of inverse protein folding or protein design, with the aim to generate amino acid sequences that would fold into an a priori determined structural fold which would enable engineering novel or enhanced biochemistry. For this task, an effective fitness function should allow identification of correct sequences that would fold into the desired structure. In this study, we showed that nonlinear fitness function for protein design can be constructed using a rectangular kernel with a basis set of proteins and decoys chosen a priori. The full landscape for a large number of protein folds can be captured using only 480 native proteins and 3,200 non-protein decoys via a finite Newton method. A blind test of a simplified version of fitness function for sequence design was carried out to discriminate simultaneously 428 native sequences not homologous to any training proteins from 11 million challenging protein-like decoys. This simplified function correctly classified 408 native sequences (20 misclassifications, 95% correct rate), which outperforms several other statistical linear scoring function and optimized linear function. Our results further suggested that for the task of global sequence design of 428 selected proteins, the search space of protein shape and sequence can be effectively parametrized with just about 3,680 carefully chosen basis set of proteins and decoys, and we showed in addition that the overall landscape is not overly sensitive to the specific choice of this set. Our results can be generalized to construct other types of fitness landscape.     

Maximum Entropy,Word-Frequency,Chinese Characters,and Multiple Meanings

The word-frequency distribution of a text written by an author is well accounted for by a maximum entropy distribution, the RGF (random group formation)-prediction. The RGF-distribution is completely determined by the a priori values of the total number of words in the text (M), the number of distinct words (N) and the number of repetitions of the most common word (k_max). It is here shown that this maximum entropy prediction also describes a text written in Chinese characters. In particular it is shown that although the same Chinese text written in words and Chinese characters have quite differently shaped distributions, they are nevertheless both well predicted by their respective three a priori characteristic values. It is pointed out that this is analogous to the change in the shape of the distribution when translating a given text to another language. Another consequence of the RGF-prediction is that taking a part of a long text will change the input parameters (M, N, k_max) and consequently also the shape of the frequency distribution. This is explicitly confirmed for texts written in Chinese characters. Since the RGF-prediction has no system-specific information beyond the three a priori values (M, N, k_max), any specific language characteristic has to be sought in systematic deviations from the RGF-prediction and the measured frequencies. One such systematic deviation is identified and, through a statistical information theoretical argument and an extended RGF-model, it is proposed that this deviation is caused by multiple meanings of Chinese characters. The effect is stronger for Chinese characters than for Chinese words. The relation between Zipf’s law, the Simon-model for texts and the present results are discussed.     

Structural insights into the interaction of antifungal peptides and ergosterol containing fungal membrane

The treatment of invasive drug-resistant and potentially life-threatening fungal infections is limited to few therapeutic options that are usually associated with severe side effects. The development of new effective antimycotics with a more tolerable side effect profile is therefore of utmost clinical importance. Here, we used a combination of complementary in vitro assays and structural analytical methods to analyze the interaction of the de novo antimicrobial peptide VG16KRKP with the sterol moieties of biological cell membranes. We demonstrate that VG16KRKP disturbs the structural integrity of fungal membranes both in vitro and in model membrane system containing ergosterol along with phosphatidylethanolamine lipid and exhibits broad-spectrum antifungal activity. As revealed by systematic structure-function analysis of mutated VG16KRKP analogs, a specific pattern of basic and hydrophobic amino acid side chains in the primary peptide sequence determines the selectivity of VG16KRKP for fungal specific membranes.     

Optimism as a Prior Belief about the Probability of Future Reward

Optimists hold positive a priori beliefs about the future. In Bayesian statistical theory, a priori beliefs can be overcome by experience. However, optimistic beliefs can at times appear surprisingly resistant to evidence, suggesting that optimism might also influence how new information is selected and learned. Here, we use a novel Pavlovian conditioning task, embedded in a normative framework, to directly assess how trait optimism, as classically measured using self-report questionnaires, influences choices between visual targets, by learning about their association with reward progresses. We find that trait optimism relates to an a priori belief about the likelihood of rewards, but not losses, in our task. Critically, this positive belief behaves like a probabilistic prior, i.e. its influence reduces with increasing experience. Contrary to findings in the literature related to unrealistic optimism and self-beliefs, it does not appear to influence the iterative learning process directly.     

On the Use of Distance in the Taxonomic Study of Critical Plant Groups—Case Studies of Western European Orchidaceae

Four distance coefficients are compared on four data sets composed of samples coming from western European populations of the genera Dactylorhiza, Orchis and Epipactis (Orchidaceae). The performance of the distance coefficients is evaluated through: (a) the quality of clusters obtained by five classical methods (as compared to a priori classification), (b) the Mantel statistic with respect to an a priori distance matrix resulting from previous knowledge, (c) the result obtained with the k-means method, and (d) principal coordinate diagrams. It appears that: (a) the Mahalanobis distance based on the pooled dispersion matrix performs best on the whole; (b) a distance based on the recently developed Common Principal Component model, used with a log transformation, also provides useful information and performs best on the largest data set; (c) the Gölz and Reinhard taxonomic distance, widely used among orchidologists, is attractive for its simplicity, yet good performance and the valuable information it provides, despite its theoretical shortcomings. A brief taxonomic discussion is made on the results obtained for the Dactylorhiza samples, especially about samples whose identification was in doubt.     

SMART: Unique Splitting-While-Merging Framework for Gene Clustering

Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.     

Estimating the sensitivity of cervical cytology: errors of interpretation and test limitations

The objective of this study was to estimate: (i) the sensitivity of cytologists in recognizing abnormal smears; (ii) the sensitivity of cervical cytology as a method of detecting abnormal smears among those obtained in the presence of cervical intraepithelial neoplasia (CIN). Study subjects were 61 women with a histologically confirmed CIN identified through colpohistological and cytologic screening. For objective (i) new smears were taken from study subjects just before treatment, mixed with routine preparations, interpreted by unaware cytologists and then blindly reviewed by a group of three expert supervisors, who reached a consensus diagnosis. Cytologists classified as positive for squamous intraepithelial lesion (SIL) 30 of the 34 smears judged as positive by supervisors (100% of smears classified as high-grade and 67% of smears classified as low-grade SIL by the supervisors). Our approach, based on creating a set of smears with a high a priori probability of being positive, proved to be an efficient way of estimating errors of interpretation. For objective (ii), smears taken at the moment of diagnosis, just before biopsy, were also reviewed by the same supervisors. These CIN cases were identified among asymptomatic women independently of cytological findings and results are therefore not subject to verification bias. Among the 33 histological CINII/III, four (12%) smears had no atypical cells (three negatives and one unsatisfactory) at review. The same proportion was 26% (four negatives and one unsatisfactory) among the 19 histological CINI. No significant differences in smear content were found between the seven ‘false negatives’ and a sample of ‘true positives’ and ‘true negatives’ for a number of formal adequacy criteria (including presence of endocervical cells). Strong differences were found between positive smears taken just before biopsy and those taken just before treatment (in 11 women the first smear only was positive, while the opposite was never observed), suggesting an effect of punch biopsy in removing lesions.