Level scheduling under limited resequencing flexibility

A mixed-model assembly line requires the solution of a short-term sequencing problem, which decides on the succession of different models launched down the line. A famous solution approach stemming from the Toyota Production System is the so-called Level Scheduling (LS), which aims to distribute the part consumption induced by a model sequence evenly over the planning horizon. LS attracted a multitude of different researchers, who, however, invariably treat initial sequence planning where all degrees of freedom in assigning models to production cycles exist. In the real-world, conflicting objectives and restrictions of preceding production stages, i.e., body and paint shop, simultaneously need to be considered and perturbations of an initial sequence will regularly occur, so that the sequencing problem often becomes a resequencing problem. Here, a given model sequence is to be reshuffled with the help of resequencing buffers (denoted as pull-off tables). This paper shows how to adapt famous solution approaches for alternative LS problems, namely the Product-Rate-Variation (PRV) and the Output-Rate-Variation (ORV) problem, if the (re-)assignment of models to cycles is restricted by the given number of pull-off tables. Furthermore, the effect of increasing re-sequencing flexibility is investigated, so that the practitioner receives decision support for buffer dimensioning, and the ability of the PRV in reasonably approximating the more detailed ORV in a resequencing environment is tested.     

Part feeding at high-variant mixed-model assembly lines

The part feeding problem at automotive assembly plants deals with the timely supply of parts to the designated stations at the assembly line. According to the just-in-time principle, buffer storages at the line are frequently refilled with parts retrieved from a central storage area. In the industrial application at hand, this is accomplished by means of an internal shuttle system which supplies the various stations with the needed parts based on a given assembly sequence. The main objective is to minimize the required number of shuttle drivers. To solve this in-house transportation problem, a heuristic solution procedure is developed which is based on the decomposition of the entire planning problem into two stages. First, transportation orders are derived from the given assembly sequence. In the second stage, these orders are assigned to tours of the shuttle system taking transportation capacity restrictions, due dates and tour scheduling constraints into account. Numerical results show that the proposed heuristic solves even large-sized problem instances in short computational time. Benchmark comparisons with Kanban systems reveal the superiority of the proposed predictive part feeding approach.     

Dynamic light scattering of native silk fibroin solution extracted from different parts of the middle division of the silk gland of the Bombyx mori silkworm

Dynamic light scattering (DLS) measurements were performed on aqueous solutions of native silk fibroin extracted from three parts, the posterior (MP), the middle (MM), and the anterior parts (MA), of the middle division (M) of the silk gland of the Bombyx mori silkworm to study the dynamics and aggregation properties of silk fibroin. In the MP part, fibroin molecules are present as aggregates (or clusters) being composed of several large protein complexes or elementary unit (EU), which are further associated to make a large assembly connected via divalent metallic ions. In the MM part, such clusters of EU take more compact structure, and finally in the MA part, clusters disappear, but EUs are more or less aligned to keep the assembly, and the EU takes the conformation of wormlike cylinder capped with hemispheres at both ends. The overall conformational change in solution structure was interpreted as being due to the change in ionic environment in the solution. DLS study was also performed on regenerated silk fibroin solutions, which revealed that fibroin is present as a single molecule dominantly and their association behavior seems completely different from that of native samples and does not depend on types and concentration of added metallic ions.     

基于Golden Gate技术的齐整小核菌转录单元高效组装系统

【目的】为齐整小核菌代谢工程研究建立高效的转录单元组装系统。【方法】通过应用Golden Gate技术,以mobius assembly为基础,分别设计并构建DNA元件标准化接口改造、单转录单元组装、应用质粒(多转录单元)组装等功能的载体,从而形成一套完整的多转录单元组装系统。【结果】构建了2个用于DNA元件标准化接口改造的Level 0载体,4个用于单转录单元组装的Level 1载体,4个用于应用质粒组装的Level 2载体和13个应用质粒组装的辅助质粒。然后应用此系统为齐整小核菌组装了若干经过标准化接口改造的DNA元件质粒、单转录单元质粒和硬葡聚糖相关基因的功能分析质粒。所构建的最终应用质粒可以同时适用于齐整小核菌的根癌农杆菌介导转化法、电穿孔转化法和原生质体转化法。【结论】此质粒系统具有强大的DNA设计、组装和容纳能力,为未来齐整小核菌代谢工程和功能基因组学研究提供了高效的质粒构建技术平台。     

Balancing and Scheduling Mixed-Model U-Shaped Production Lines

The production line considered in this paper is a U-shaped, mixed-model, asynchronous line where assembly and fabrication tasks are performed to produce a variety of different discrete products or models in a just-in-time (JIT) environment. Two important problems occur routinely with these lines. The first is the assignment of tasks to stations on the line—the line balancing problem—and the second is the selection of the sequence in which models will be produced—the model sequencing problem. The model sequence cannot be set independently of the line balance, because different models require different tasks and the same tasks have different completion times for different models, and, in the JIT environment, the model sequence cannot be set independently of the schedules of other lines and production facilities. JIT uses a pull rather than a push system of production control, which means that the model sequence at the U-shaped mixed-model final assembly line sets the schedules at the other production facilities. JIT requires these latter schedules to be “level” and this requirement imposes an additional constraint on the model sequence. The effect of these two conditions is to require that the line-balancing and model-sequencing problems be solved simultaneously. In this article, we model the joint problem and present a solution algorithm for solving instances of practical size.     

Estimation of Part Waiting Time and Fleet Sizing in AGV Systems

As manufacturing systems have grown in size and complexity, material flow control has become one of the key issues for system efficiency, and determination of the number of vehicles required is an important issue in the design of the AGV (automatic guided vehicle) systems for automated material flow control. In an AGV system, a part issues a delivery request for its transportation, and then an empty vehicle is assigned based on a pre-determined vehicle selection rule and provides delivery service.This research presents a fleet sizing procedure for an AGV system with multiple pickup and delivery stations. A queueing model is used to estimate part waiting times. The fleet sizing procedure estimates the minimum number of vehicles needed to ensure a predefined part waiting time limit. While most stochastic models assume first-come-first-served or random vehicle selection rules for the selection of an empty vehicle, this model considers such additional rules as the nearest vehicle selection rule, which is the most popular among all vehicle selection rules. The performance of the proposed model is examined through computational experiments.     

Planning the routing mix in FASs to minimize total transportation time

The routing mix problem in flexible assembly systems is considered. The problem consists of assigning the operations for each part to the machines, with the two objectives of balancing the machine workloads and minimizing the burden of the transportation system. These two objectives are sometimes conflicting, since the latter tends to support assigning operations to the same machine(s) as much as possible, and this may be bad for workload balancing. A linear programming problem is presented that, given a constraint on the workload of each machine, finds one solution that minimizes the overall time spent moving the parts from one machine to another. Since such a linear program may have an exponential number of variables, an efficient column generation technique to solve the problem is devised. The efficiency of the method is validated by experiments on a large number of random problems.     

动态规划算法对GenoCAD设计结果的优化

GenoCAD(www.genocad.com)是一种基于Web的免费合成生物学设计软件,用它可以进行表达载体及人工基因网络设计。持续点击代表各种合成生物学标准“零件”的图标,以一种语法进行设计,最后就可以得到由数十个功能片段组成的复杂质粒载体。但是在GenoCAD中,每一类的合成生物学标准“零件”数量众多。随着这些标准“零件”的不断开发,其数量也在进一步增加,目前选择合适的“零件”组装成功能性的质粒载体费时费力并且容易发生错误。在进行载体设计的最后阶段,从众多的“零件”中选择合适的往往比较困难。为解决这一问题,本文采用了自然语言处理的统计语言模型,它最初用于自然语言识别,用来估算一组词串成为一个正确语句的概率的大小。本文最后以该模型为基础应用动态规划算法优化质粒载体设计,从众多的选项中找出最优者。利用这一方法可以减少进行生物学实验的冗余操作,从而减少载体构建过程中的花费。     

The "block" approach in x-ray diffusion dispersion as a method of studying the packing of secondary structure elements in globular proteins

To calculate large angle scattering intensity of biopolymers in solution a "block" method of modeling the globular proteins structures is suggested: conformation of protein alpha-helical and beta-structural parts are described in detail, whereas the remaining part of the macromolecule is substituted by a continuum with homogeneous electron density. A comparison of large-angle scattering curves on the basis of the "block" method and the exact structure was made for a number of alpha-helical and beta-structural globular proteins. It is shown that there is a qualitative agreement between the "exact" and model curves.     

Dawn of a new day: The role of children in the assimilation of new technologies throughout the Lower Paleolithic

In this paper, I contend that children had a unique position in prehistoric social systems, functioning as primary assimilators of new technologies. Their role is especially crucial at significant turning points in history, due to a number of childhood-cognitive mechanisms that are activated in learning and playing while engaging in innovative activity. I suggest that these mechanisms developed as part of an evolutionary process that has enabled humans to better adapt to change and prosper. This line of thinking is demonstrated through a synthesis of evolutionary, cognitive-psychological models and a case study from the archaeological record of the Levantine late Lower Paleolithic. In this time, humans developed a set of creative innovations which had to be learned and assimilated, such as the innovative production of blades. I argue that these cultural changes were successfully assimilated by groups inhabiting the Levant due to the enhancement of well-established learning mechanisms, in which children played a significant role. This role might have given them a unique status in their group – as preserving old traditions practiced by their ancestors but also as active agents, part of a collective group effort of tackling present and future challenges.     

Lipophilic phosphonium-lanthanide compounds with magnetic, luminescent, and tumor targeting properties

Multifunctional phosphonium-lanthanide compounds that simultaneously possess paramagnetism, luminescence, and tumor mitochondrial targeting properties were prepared by use of a facile method. These compounds were fully characterized by use of ¹H, ¹³C, ³¹P NMR, FT-IR, and elemental analyses. The thermal properties of these compounds including melting points and decomposition temperatures were investigated using DSC and TGA analyses. In addition, the paramagnetism, luminescence, and tumor targeting properties of these multifunctional compounds were confirmed by respective use of SQUID, fluorescence, and cell cytotoxicity studies. All compounds exhibited paramagnetism at room temperature, which could provide target delivery of these compounds to parts of the body containing tumor cells using a strong external magnetic field. In addition, these compounds display two major characteristic emissions originating from Dy^3 +, which can be utilized for imaging tumor cells. The IC₅₀ values of these compounds measured against normal breast cell line (Hs578Bst) are significantly greater than those measured against the corresponding carcinoma breast cell line (Hs578T), clearly indicating the selective tumor targeting properties of these compounds. Confocal fluorescence microscopy studies were used to confirm the yellowish-green fluorescence corresponding to the emission of dysprosium thiocyanate anion within cancer cells upon exposure of cancer cell lines such as human pancreatic carcinoma cell line (MIAPaCa-2) and human breast carcinoma (MDA-MB-231) to a solution of these phosphonium-dysprosium compounds.     

Practical use of modified maximum likelihoods for stratified data

Stratified data arise in several settings, such as longitudinal studies or multicenter clinical trials. Between-strata heterogeneity is usually addressed by random effects models, but an alternative approach is given by fixed effects models, which treat the incidental nuisance parameters as fixed unknown quantities. This approach presents several advantages, like computational simplicity and robustness to confounding by strata. However, maximum likelihood estimates of the parameter of interest are typically affected by incidental parameter bias. A remedy to this is given by the elimination of stratum-specific parameters by exact or approximate conditioning. The latter solution is afforded by the modified profile likelihood, which is the method applied in this paper. The aim is to demonstrate how the theory of modified profile likelihoods provides convenient solutions to various inferential problems in this setting. Specific procedures are available for different kinds of response variables, and they are useful both for inferential purposes and as a diagnostic method for validating random effects models. Some examples with real data illustrate these points.     

Scheduling parallel machines with major and minor setup times

This article discusses the problem of scheduling a large set of parts on an FMS so as to minimize the total completion time. Here, the FMS consists of a set of parallel identical machines. Setup time is incurred whenever a machine switches from one type of part to another. The setup time may be large or small depending on whether or not the two part types belong to the same family. This article describes a fast heuristic for this scheduling problem and derives a lower bound on the optimal solution. In computational tests using random data and data from an IBM card test line, the heuristic archieves nearly optimal schedules.     

The use of field emission in-lens scanning electron microscopy to study the steps of assembly of the nuclear envelope in vitro.

At mitosis the nuclear envelope (NE) is disassembled to allow chromosome separation. In telophase it is reassembled as the chromosomes decondense. Cell-free extracts of Xenopus eggs have been used extensively to study assembly of the NE and the nuclear pore complexes (NPCs), providing several models for the steps involved. The NE is a surface structure which in cell-free extracts is easily exposed. It is appropriate, therefore, to use a surface imaging technique to study NE dynamics. Field emission in-lens scanning electron microscopy (FEISEM) provides the opportunity to image surfaces, directly, and to visualise details of structures such as the NPC. Here we show the feasibility and value of FEISEM to study the steps of NE formation. Nuclei have been assembled in vitro and fixed at different time points during assembly, followed by conductive staining, platinum coating, and visualisation by FEISEM. Changes on the nuclear surface with time are shown. Details of the surface of chromatin and the cytoplasmic face of NPC structure are demonstrated without the need to isolate the structures from the nucleus.     

Helicobacter infection induces podosome assembly in primary hepatocytes in vitro

Helicobacter pylori (H. pylori) infection may contribute to many extragastric diseases including liver cirrhosis and hepatocellular carcinoma. However, the exact mechanism by which H. pylori induces the liver damage is largely unknown. We used cultured mouse primary hepatocytes as an in vitro model to investigate different aspects of liver physiology and pathology. In this study, we show that primary hepatocytes are able to assemble actin-based cytoskeletal structures called podosomes at the ventral plasma membrane. These structures are positive for podosome markers such as cortactin, vinculin and integrins and comprise proteolytic potential. Infection with the pathogen H. pylori further stimulates the formation of podosomes in primary hepatocytes. The use of pharmacological inhibitors reveals that this response is mediated, at least in part, by TGFβ, a cytokine known to regulate podosome formation in endothelial cells. Similar results are obtained with the hepatoma cell line Huh7. Podosome formation is associated with increased hepatocyte degrading capacities but also with reduced cell motility. Therefore, podosome assembly translates into hepatocyte malfunction. Our study supports the hypothesis that hepatocytes can also assemble podosomes under pathological conditions in vivo.     

Work flow control in the flexible flow line

This research involves the development and evaluation of a part flow control model for a type of flexible manufacturing system (FMS) called a dedicated flexible flow line (FFL). In the FFL, all part types flow along the same path between successive machine groups. The specific objective of the part flow control model for the FFL is to minimize makespan for a given set of parts produced in a FFL near-term schedule, given fixed available buffer constraints. The control model developed in this research involved the repeated, real-time execution of a mathematical programming algorithm. The algorithm attempts to release the right mix of parts at the tight time to keep the FFL operating smoothly. The focus of the approach is directed toward managing WIP buffers for each machine group queue. The algorithm specifically incorporates stochastic disturbance factors such as machine failures. Through a limited number of simulation experiments, performance of the control model is shown to be superior to other parts releasing and control methods reported in the literature.     

Cytochrome c oxidase deficiency: Patients and animal models

Cytochrome c oxidase (COX) deficiencies are one of the most common defects of the respiratory chain found in mitochondrial diseases. COX is a multimeric inner mitochondrial membrane enzyme formed by subunits encoded by both the nuclear and the mitochondrial genome. COX biosynthesis requires numerous assembly factors that do not form part of the final complex but participate in prosthetic group synthesis and metal delivery in addition to membrane insertion and maturation of COX subunits. Human diseases associated with COX deficiency including encephalomyopathies, Leigh syndrome, hypertrophic cardiomyopathies, and fatal lactic acidosis are caused by mutations in COX subunits or assembly factors. In the last decade, numerous animal models have been created to understand the pathophysiology of COX deficiencies and the function of assembly factors. These animal models, ranging from invertebrates to mammals, in most cases mimic the pathological features of the human diseases.     

The use of field emission in-lens scanning electron microscopy to study the steps of assembly of the nuclear envelope in vitro

At mitosis the nuclear envelope (NE) is disassembled to allow chromosome separation. In telophase it is reassembled as the chromosomes decondense. Cell-free extracts of Xenopus eggs have been used extensively to study assembly of the NE and the nuclear pore complexes (NPCs), providing several models for the steps involved. The NE is a surface structure which in cell-free extracts is easily exposed. It is appropriate, therefore, to use a surface imaging technique to study NE dynamics. Field emission in-lens scanning electron microscopy (FEISEM) provides the opportunity to image surfaces, directly, and to visualise details of structures such as the NPC. Here we show the feasibility and value of FEISEM to study the steps of NE formation. Nuclei have been assembled in vitro and fixed at different time points during assembly, followed by conductive staining, platinum coating, and visualisation by FEISEM. Changes on the nuclear surface with time are shown. Details of the surface of chromatin and the cytoplasmic face of NPC structure are demonstrated without the need to isolate the structures from the nucleus.     

A diaphragm delivery device for flow microcalorimetry

A diaphragm delivery device is described which allows delivery of a reagent to a flow system at a constant or variable flow rate. The device presents only a Teflon surface to the reagent and avoids direct contact with the pump. This delivery system is used to cireumvent the serious problem of reagent interaction with the working parts of pumps used in flow microcalorimetry while retaining the convenience of switching from one solution to another. The reaction of α-chymotrypsin with the nonspecific substrate 3-(2-furyl)-acryloylimidazole is used to illustrate the advantages of the diaphragm delivery device.