Highly accurate RNA and DNA sequencing: Application to longstanding questions in aging and cancer

Thesis (Ph.D.)--University of Washington, 2016-06

Generic Technique to Generate Large Branched DNA Complexes

The inherent self-recognition properties of DNA have led to its use as a scaffold for various nanotechnology self-assembly applications, with macromolecular complexes, metallic and semiconducting nanoparticles, proteins, inter alia, being assembled onto a designed DNA scaffold. Such structures may typically comprise a number of DNA molecules organized into macromolecules. Many studies have used synthetic methods to produce the constituent DNA molecules, but this typically constrains the molecules to be no longer than around 100 base pairs (30 nm). However, applications that require larger self-assembling DNA complexes, several tens of nanometers or more, need to be generated by other techniques. Here, we present a generic technique to generate large linear, branched, and/or circular DNA macromolecular complexes. The effectiveness of this technique is demonstrated here by the use of Lambda Bacteriophage DNA as a template to generate single- and double-branched DNA structures approximately 120 nm in size.

Optimal production planning for PCB assembly

It is indisputable that printed circuit boards (PCBs) play a vital role in our daily lives. With the ever-increasing applications of PCBs, one of the crucial ways to increase a PCB manufacturer’s competitiveness in terms of operation efficiency is to minimize the production time so that the products can be introduced to the market sooner. Optimal Production Planning for PCB Assembly is the first book to focus on the optimization of the PCB assembly lines’ efficiency. This is done by: • integrating the component sequencing and the feeder arrangement problems together for both the pick-and-place machine and the chip shooter machine; • constructing mathematical models and developing an efficient and effective heuristic solution approach for the integrated problems for both types of placement machines, the line assignment problem, and the component allocation problem; and • developing a prototype of the PCB assembly planning system. The techniques proposed in Optimal Production Planning for PCB Assembly will enable process planners in the electronics manufacturing industry to improve the assembly line’s efficiency in their companies. Graduate students in operations research can familiarise themselves with the techniques and the applications of mathematical modeling after reading this advanced introduction to optimal production planning for PCB assembly.

A mathematical model for assembly line balancing model to consider disordering sequence of workstations

Purpose – A binary integer programming model for the simple assembly line balancing problem (SALBP), which is well known as SALBP-1, was formulated more than 30 years ago. Since then, a number of researchers have extended the model for the variants of assembly line balancing problem.The model is still prevalent nowadays mainly because of the lower and upper bounds on task assignment. These properties avoid significant increase of decision variables. The purpose of this paper is to use an example to show that the model may lead to a confusing solution. Design/methodology/approach – The paper provides a remedial constraint set for the model to rectify the disordered sequence problem. Findings – The paper presents proof that the assembly line balancing model formulated by Patterson and Albracht may lead to a confusing solution. Originality/value – No one previously has found that the commonly used model is incorrect.

Optimizing PCB assembly for family setup strategy

Purpose – The purpose of this paper is to investigate the optimization for a placement machine in printed circuit board (PCB) assembly when family setup strategy is adopted. Design/methodology/approach – A complete mathematical model is developed for the integrated problem to optimize feeder arrangement and component placement sequences so as to minimize the makespan for a set of PCB batches. Owing to the complexity of the problem, a specific genetic algorithm (GA) is proposed. Findings – The established model is able to find the minimal makespan for a set of PCB batches through determining the feeder arrangement and placement sequences. However, exact solutions to the problem are not practical due to the complexity. Experimental tests show that the proposed GA can solve the problem both effectively and efficiently. Research limitations/implications – When a placement machine is set up for production of a set of PCB batches, the feeder arrangement of the machine together with the component placement sequencing for each PCB type should be solved simultaneously so as to minimize the overall makespan. Practical implications – The paper investigates the optimization for PCB assembly with family setup strategy, which is adopted by many PCB manufacturers for reducing both setup costs and human errors. Originality/value – The paper investigates the feeder arrangement and placement sequencing problems when family setup strategy is adopted, which has not been studied in the literature.

PCB assembly line assignment:a genetic algorithm approach

Purpose – This paper sets out to study a production-planning problem for printed circuit board (PCB) assembly. A PCB assembly company may have a number of assembly lines for production of several product types in large volume. Design/methodology/approach – Pure integer linear programming models are formulated for assigning the product types to assembly lines, which is the line assignment problem, with the objective of minimizing the total production cost. In this approach, unrealistic assignment, which was suffered by previous researchers, is avoided by incorporating several constraints into the model. In this paper, a genetic algorithm is developed to solve the line assignment problem. Findings – The procedure of the genetic algorithm to the problem and a numerical example for illustrating the models are provided. It is also proved that the algorithm is effective and efficient in dealing with the problem. Originality/value – This paper studies the line assignment problem arising in a PCB manufacturing company in which the production volume is high.

A heuristic approach for component scheduling on a high-speed PCB assembly machine

The collect-and-place machine is one of the most widely used placement machines for assembling electronic components on the printed circuit boards (PCBs). Nevertheless, the number of researches concerning the optimisation of the machine performance is very few. This motivates us to study the component scheduling problem for this type of machine with the objective of minimising the total assembly time. The component scheduling problem is an integration of the component sequencing problem, that is, the sequencing of component placements; and the feeder arrangement problem, that is, the assignment of component types to feeders. To solve the component scheduling problem efficiently, a hybrid genetic algorithm is developed in this paper. A numerical example is used to compare the performance of the algorithm with different component grouping approaches and different population sizes.

A genetic algorithm to optimise the component placement process in the PCB assembly

In printed circuit board (PCB) assembly, the efficiency of the component placement process is dependent on two interrelated issues: the sequence of component placement, that is, the component sequencing problem, and the assignment of component types to feeders of the placement machine, that is, the feeder arrangement problem. In cases where some components with the same type are assigned to more than one feeder, the component retrieval problem should also be considered. Due to their inseparable relationship, a hybrid genetic algorithm is adopted to solve these three problems simultaneously for a type of PCB placement machines called the sequential pick-and-place (PAP) machine in this paper. The objective is to minimise the total distance travelled by the placement head for assembling all components on a PCB. Besides, the algorithm is compared with the methods proposed by other researchers in order to examine its effectiveness and efficiency.

Molecular modelling assisted design and synthesis of cyclothialidine derivatives as DNA gyrase inhibitors

Since cyclothialidine was discovered as the most active DNA gyrase inhibitor in 1994, enormous efforts have been devoted to make it into a commercial medicine by a number of pharmaceutical companies and research groups worldwide. However, no serious breakthrough has been made up to now. An essential problem involved with cyclothialidine is that though it demonstrated the potent inhibition of DNA gyrase, it showed little activity against bacteria. This probably is attributable to its inability to penetrate bacterial cell walls and membranes. We applied the TSAR programme to generate a QSAR equation to the gram-negative organisms. In that equation, LogP is profoundly indicated as the key factor influencing the cyclothialidine activity against bacteria. However, the synthesized new analogues have failed to prove that. In the structure based drug design stage, we designed a group of open chain cyclothialidine derivatives by applying the SPROUT programme and completed the syntheses. Improved activity is found in a few analogues and a 3D pharmacophore of the DNA gyrase B is proposed to lead to synthesis of the new derivatives for development of potent antibiotics.

Classification of bacterial strains based on DNA profiles

The analysis of bacterial genomes for epidemiological purposes often results in the production of a banding profile of DNA fragments characteristic of the genome under investigation. These may be produced using various methods, many of which involve the cutting or amplification of DNA into defined and reproducible characteristic fragments. It is frequently of interest to enquire whether the bacterial isolates are naturally classifiable into distinct groups based on their DNA profiles. A major problem with this approach is whether classification or clustering of the data is even appropriate. It is always possible to classify such data but it does not follow that the strains they represent are ‘actually’ classifiable into well-defined separate parts. Hence, the act of classification does not in itself answer the question: do the strains consist of a number of different distinct groups or species or do they merge imperceptibly into one another because DNA profiles vary continuously? Nevertheless, we may still wish to classify the data for ‘convenience’ even though strains may vary continuously, and such a classification has been called a ‘dissection’. This Statnote discusses the use of classificatory methods in analyzing the DNA profiles from a sample of bacterial isolates.

Recent Results on Stability Analysis of an Optimal Assembly Line Balance

Two assembly line balancing problems are addressed. The first problem (called SALBP-1) is to minimize number of linearly ordered stations for processing n partially ordered operations V = {1, 2, ..., n} within the fixed cycle time c. The second problem (called SALBP-2) is to minimize cycle time for processing partially ordered operations V on the fixed set of m linearly ordered stations. The processing time ti of each operation i ∈V is known before solving problems SALBP-1 and SALBP-2. However, during the life cycle of the assembly line the values ti are definitely fixed only for the subset of automated operations V\V . Another subset V ⊆ V includes manual operations, for which it is impossible to fix exact processing times during the whole life cycle of the assembly line. If j ∈V , then operation times tj can differ for different cycles of the production process. For the optimal line balance b of the assembly line with operation times t1, t2, ..., tn, we investigate stability of its optimality with respect to possible variations of the processing times tj of the manual operations j ∈ V .

A DNA Codification for Genetic Algorithms Simulation

In this paper we propose a model of encoding data into DNA strands so that this data can be used in the simulation of a genetic algorithm based on molecular operations. DNA computing is an impressive computational model that needs algorithms to work properly and efficiently. The first problem when trying to apply an algorithm in DNA computing must be how to codify the data that the algorithm will use. In a genetic algorithm the first objective must be to codify the genes, which are the main data. A concrete encoding of the genes in a single DNA strand is presented and we discuss what this codification is suitable for. Previous work on DNA coding defined bond-free languages which several properties assuring the stability of any DNA word of such a language. We prove that a bond-free language is necessary but not sufficient to codify a gene giving the correct codification.

EnDNA-Prot:identification of DNA-binding proteins by applying ensemble learning

DNA-binding proteins are crucial for various cellular processes, such as recognition of specific nucleotide, regulation of transcription, and regulation of gene expression. Developing an effective model for identifying DNA-binding proteins is an urgent research problem. Up to now, many methods have been proposed, but most of them focus on only one classifier and cannot make full use of the large number of negative samples to improve predicting performance. This study proposed a predictor called enDNA-Prot for DNA-binding protein identification by employing the ensemble learning technique. Experiential results showed that enDNA-Prot was comparable with DNA-Prot and outperformed DNAbinder and iDNA-Prot with performance improvement in the range of 3.97-9.52% in ACC and 0.08-0.19 in MCC. Furthermore, when the benchmark dataset was expanded with negative samples, the performance of enDNA-Prot outperformed the three existing methods by 2.83-16.63% in terms of ACC and 0.02-0.16 in terms of MCC. It indicated that enDNA-Prot is an effective method for DNA-binding protein identification and expanding training dataset with negative samples can improve its performance. For the convenience of the vast majority of experimental scientists, we developed a user-friendly web-server for enDNA-Prot which is freely accessible to the public. © 2014 Ruifeng Xu et al.

The Production Scheduling in Assembly System with Evolutionary Algorithm

In this paper an evolutionary algorithm is proposed for solving the problem of production scheduling in assembly system. The aim of the paper is to investigate a possibility of the application of evolutionary algorithms in the assembly system of a normally functioning enterprise producing household appliances to make the production graphic schedule.

A novel algorithm of posture best fit based on key characteristics for large components assembly

Measurement and variation control of geometrical Key Characteristics (KCs), such as flatness and gap of joint faces, coaxiality of cabin sections, is the crucial issue in large components assembly from the aerospace industry. Aiming to control geometrical KCs and to attain the best fit of posture, an optimization algorithm based on KCs for large components assembly is proposed. This approach regards the posture best fit, which is a key activity in Measurement Aided Assembly (MAA), as a two-phase optimal problem. In the first phase, the global measurement coordinate system of digital model and shop floor is unified with minimum error based on singular value decomposition, and the current posture of components being assembly is optimally solved in terms of minimum variation of all reference points. In the second phase, the best posture of the movable component is optimally determined by minimizing multiple KCs' variation with the constraints that every KC respectively conforms to its product specification. The optimal models and the process procedures for these two-phase optimal problems based on Particle Swarm Optimization (PSO) are proposed. In each model, every posture to be calculated is modeled as a 6 dimensional particle (three movement and three rotation parameters). Finally, an example that two cabin sections of satellite mainframe structure are being assembled is selected to verify the effectiveness of the proposed approach, models and algorithms. The experiment result shows the approach is promising and will provide a foundation for further study and application. © 2013 The Authors.