Computational design of orthogonal microRNAs for synthetic biology

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Upcoming applications of synthetic biology will require access to a wide array of robust genetic components (parts). The logic of a genetic system is encoded with regulatory elements such as pairs of transcription factors:promoters, miRNAs:target sites, or ribozymes:aptamers among others. Due to a relatively simple form and mode of operation of miRNAs, it is possible to design their synthetic variants. Out of all possible miRNA sequences the ones chosen should perform efficiently and should avoid cross-talk with both the host system circuits and within the imported synthetic ones. In this work, a computational method involving a series of heuristics is developed that can be used to design ensembles of such sequences depending on the host transcriptome. As an example, an ensemble of eight such miRNA sequences is produced using this method for use in a human host. Those have then been validated experimentally against the above-mentioned requirements by transfection into HEK 293 cells and flow cytometry measurements of fluorescent markers. The produced sequences are available for use from pENTR vectors of the Gateway cloning system. The required computations were facilitated by a modern cluster computing system—Kaichu—especially developed for this project, but fit for general purpose use and available under an open-source license.EPSR

Research Trends and Outlooks in Assembly Line Balancing Problems

This paper presents the findings from the survey of articles published on the assembly line balancing problems (ALBPs) during 2014-2018. Before proceeding a comprehensive literature review, the ineffectiveness of the previous ALBP classification structures is discussed and a new classification scheme based on the layout configurations of assembly lines is subsequently proposed. The research trend in each layout of assembly lines is highlighted through the graphical presentations. The challenges in the ALBPs are also pinpointed as a technical guideline for future research works

Theory and simulation of DNA-coated colloids: a guide for rational design.

By exploiting the exquisite selectivity of DNA hybridization, DNA-coated colloids (DNACCs) can be made to self-assemble in a wide variety of structures. The beauty of this system stems largely from its exceptional versatility and from the fact that a proper choice of the grafted DNA sequences yields fine control over the colloidal interactions. Theory and simulations have an important role to play in the optimal design of self assembling DNACCs. At present, the powerful model-based design tools are not widely used, because the theoretical literature is fragmented and the connection between different theories is often not evident. In this Perspective, we aim to discuss the similarities and differences between the different models that have been described in the literature, their underlying assumptions, their strengths and their weaknesses. Using the tools described in the present Review, it should be possible to move towards a more rational design of novel self-assembling structures of DNACCs and, more generally, of systems where ligand-receptor are used to control interactions.This is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5CP06981

Spectroscopic Studies of Charge Dynamics in Non-Fullerene Organic Solar Cells

Organic solar cells (OSCs) are a promising technology for emission-free electricity supply. However, low power conversion efficiencies and poor device stabilities have so far prevented widespread commercial applications. Remarkable progress has been made recently by the development of non-fullerene electron acceptor materials. They benefit from good tunablity of energy levels as well as greater thermal and photochemical stability, and remarkable power conversion efficiencies of up to 16.5 % have been achieved. Furthermore, they have shown efficient charge separation with negligible energy loss, overcoming one of the crucial limitations of fullerene based OSC. Here, we present a study on the charge generation, separation, and recombination dynamics of non-fullerene solar cells. We investigate the model system P3TEA:SF-PDI$_2$ via pump-probe spectroscopy and time-resolved photoluminescence spectroscopy. We find ultrafast charge generation as well as regeneration of singlets via encounters of free electrons and holes. Additionally, we observe slow ($\sim$ 100 ps) and thermally activated charge separation from vibrationally relaxed charge transfer exciton (CTE) states. To directly track the CTE population, we employ pump-push-probe spectroscopy. Our results suggest that singlet excitons, CTE states, and free charges form an equilibrium, with reversible interconversion between them. These systems are therefore not limited by the need to provide excess energy to overcome the Coulomb binding energy. Thus, future efforts to improve efficiencies should focus on removing energy offsets and irreversible processes, such as non-radiative recombination. Furthermore, we study PBDB-T:ITIC, a material that was used in the first non-fullerene cell that exceeded 10 % efficiency. We find that the charge generation occurs on a $\sim$ 10 ps timescale, several orders of magnitude slower than in efficient fullerene-based systems. Additionally, we identify two different pathways for non-radiative decay: triplet generation in the polymer and trap-assisted charge recombination.The research for this thesis was funded by the Winton Programme for the Physics of Sustainability and the European Research Council

Genetic algorithm-neural network: feature extraction for bioinformatics data.

With the advance of gene expression data in the bioinformatics field, the questions which frequently arise, for both computer and medical scientists, are which genes are significantly involved in discriminating cancer classes and which genes are significant with respect to a specific cancer pathology. Numerous computational analysis models have been developed to identify informative genes from the microarray data, however, the integrity of the reported genes is still uncertain. This is mainly due to the misconception of the objectives of microarray study. Furthermore, the application of various preprocessing techniques in the microarray data has jeopardised the quality of the microarray data. As a result, the integrity of the findings has been compromised by the improper use of techniques and the ill-conceived objectives of the study. This research proposes an innovative hybridised model based on genetic algorithms (GAs) and artificial neural networks (ANNs), to extract the highly differentially expressed genes for a specific cancer pathology. The proposed method can efficiently extract the informative genes from the original data set and this has reduced the gene variability errors incurred by the preprocessing techniques. The novelty of the research comes from two perspectives. Firstly, the research emphasises on extracting informative features from a high dimensional and highly complex data set, rather than to improve classification results. Secondly, the use of ANN to compute the fitness function of GA which is rare in the context of feature extraction. Two benchmark microarray data have been taken to research the prominent genes expressed in the tumour development and the results show that the genes respond to different stages of tumourigenesis (i.e. different fitness precision levels) which may be useful for early malignancy detection. The extraction ability of the proposed model is validated based on the expected results in the synthetic data sets. In addition, two bioassay data have been used to examine the efficiency of the proposed model to extract significant features from the large, imbalanced and multiple data representation bioassay data

Models and Algorithms for the Optimisation of Replenishment, Production and Distribution Plans in Industrial Enterprises

Tesis por compendio[ES] La optimización en las empresas manufactureras es especialmente importante, debido a las grandes inversiones que realizan, ya que a veces estas inversiones no obtienen el rendimiento esperado porque los márgenes de beneficio de los productos son muy ajustados. Por ello, las empresas tratan de maximizar el uso de los recursos productivos y financieros minimizando el tiempo perdido y, al mismo tiempo, mejorando los flujos de los procesos y satisfaciendo las necesidades del mercado. El proceso de planificación es una actividad crítica para las empresas. Esta tarea implica grandes retos debido a los cambios del mercado, las alteraciones en los procesos de producción dentro de la empresa y en la cadena de suministro, y los cambios en la legislación, entre otros. La planificación del aprovisionamiento, la producción y la distribución desempeña un papel fundamental en el rendimiento de las empresas manufactureras, ya que una planificación ineficaz de los proveedores, los procesos de producción y los sistemas de distribución contribuye a aumentar los costes de los productos, a alargar los plazos de entrega y a reducir los beneficios. La planificación eficaz es un proceso complejo que abarca una amplia gama de actividades para garantizar que los equipos, los materiales y los recursos humanos estén disponibles en el momento y el lugar adecuados. Motivados por la complejidad de la planificación en las empresas manufactureras, esta tesis estudia y desarrolla herramientas cuantitativas para ayudar a los planificadores en los procesos de la planificación del aprovisionamiento, producción y distribución. Desde esta perspectiva, se proponen modelos realistas y métodos eficientes para apoyar la toma de decisiones en las empresas industriales, principalmente en las pequeñas y medianas empresas (PYMES). Las aportaciones de esta tesis suponen un avance científico basado en una exhaustiva revisión bibliográfica sobre la planificación del aprovisionamiento, la producción y la distribución que ayuda a comprender los principales modelos y algoritmos utilizados para resolver estos planes, y pone en relieve las tendencias y las futuras direcciones de investigación. También proporciona un marco holístico para caracterizar los modelos y algoritmos centrándose en la planificación de la producción, la programación y la secuenciación. Esta tesis también propone una herramienta de apoyo a la decisión para seleccionar un algoritmo o método de solución para resolver problemas concretos de la planificación del aprovisionamiento, producción y distribución en función de su complejidad, lo que permite a los planificadores no duplicar esfuerzos de modelización o programación de técnicas de solución. Por último, se desarrollan nuevos modelos matemáticos y enfoques de solución de última generación, como los algoritmos matheurísticos, que combinan la programación matemática y las técnicas metaheurísticas. Los nuevos modelos y algoritmos comprenden mejoras en términos de rendimiento computacional, e incluyen características realistas de los problemas del mundo real a los que se enfrentan las empresas de fabricación. Los modelos matemáticos han sido validados con un caso de una importante empresa del sector de la automoción en España, lo que ha permitido evaluar la relevancia práctica de estos novedosos modelos utilizando instancias de gran tamaño, similares a las existentes en la empresa objeto de estudio. Además, los algoritmos matheurísticos han sido probados utilizando herramientas libres y de código abierto. Esto también contribuye a la práctica de la investigación operativa, y proporciona una visión de cómo desplegar estos métodos de solución y el tiempo de cálculo y rendimiento de la brecha que se puede obtener mediante el uso de software libre o de código abierto.[CA] L'optimització a les empreses manufactureres és especialment important, a causa de les grans inversions que realitzen, ja que de vegades aquestes inversions no obtenen el rendiment esperat perquè els marges de benefici dels productes són molt ajustats. Per això, les empreses intenten maximitzar l'ús dels recursos productius i financers minimitzant el temps perdut i, alhora, millorant els fluxos dels processos i satisfent les necessitats del mercat. El procés de planificació és una activitat crítica per a les empreses. Aquesta tasca implica grans reptes a causa dels canvis del mercat, les alteracions en els processos de producció dins de l'empresa i la cadena de subministrament, i els canvis en la legislació, entre altres. La planificació de l'aprovisionament, la producció i la distribució té un paper fonamental en el rendiment de les empreses manufactureres, ja que una planificació ineficaç dels proveïdors, els processos de producció i els sistemes de distribució contribueix a augmentar els costos dels productes, allargar els terminis de lliurament i reduir els beneficis. La planificació eficaç és un procés complex que abasta una àmplia gamma d'activitats per garantir que els equips, els materials i els recursos humans estiguen disponibles al moment i al lloc adequats. Motivats per la complexitat de la planificació a les empreses manufactureres, aquesta tesi estudia i desenvolupa eines quantitatives per ajudar als planificadors en els processos de la planificació de l'aprovisionament, producció i distribució. Des d'aquesta perspectiva, es proposen models realistes i mètodes eficients per donar suport a la presa de decisions a les empreses industrials, principalment a les petites i mitjanes empreses (PIMES). Les aportacions d'aquesta tesi suposen un avenç científic basat en una exhaustiva revisió bibliogràfica sobre la planificació de l'aprovisionament, la producció i la distribució que ajuda a comprendre els principals models i algorismes utilitzats per resoldre aquests plans, i posa de relleu les tendències i les futures direccions de recerca. També proporciona un marc holístic per caracteritzar els models i algorismes centrant-se en la planificació de la producció, la programació i la seqüenciació. Aquesta tesi també proposa una eina de suport a la decisió per seleccionar un algorisme o mètode de solució per resoldre problemes concrets de la planificació de l'aprovisionament, producció i distribució en funció de la seua complexitat, cosa que permet als planificadors no duplicar esforços de modelització o programació de tècniques de solució. Finalment, es desenvolupen nous models matemàtics i enfocaments de solució d'última generació, com ara els algoritmes matheurístics, que combinen la programació matemàtica i les tècniques metaheurístiques. Els nous models i algoritmes comprenen millores en termes de rendiment computacional, i inclouen característiques realistes dels problemes del món real a què s'enfronten les empreses de fabricació. Els models matemàtics han estat validats amb un cas d'una important empresa del sector de l'automoció a Espanya, cosa que ha permés avaluar la rellevància pràctica d'aquests nous models utilitzant instàncies grans, similars a les existents a l'empresa objecte d'estudi. A més, els algorismes matheurístics han estat provats utilitzant eines lliures i de codi obert. Això també contribueix a la pràctica de la investigació operativa, i proporciona una visió de com desplegar aquests mètodes de solució i el temps de càlcul i rendiment de la bretxa que es pot obtindre mitjançant l'ús de programari lliure o de codi obert.[EN] Optimisation in manufacturing companies is especially important, due to the large investments they make, as sometimes these investments do not obtain the expected return because the profit margins of products are very tight. Therefore, companies seek to maximise the use of productive and financial resources by minimising lost time and, at the same time, improving process flows while meeting market needs. The planning process is a critical activity for companies. This task involves great challenges due to market changes, alterations in production processes within the company and in the supply chain, and changes in legislation, among others. Planning of replenishment, production and distribution plays a critical role in the performance of manufacturing companies because ineffective planning of suppliers, production processes and distribution systems contributes to higher product costs, longer lead times and less profits. Effective planning is a complex process that encompasses a wide range of activities to ensure that equipment, materials and human resources are available in the right time and the right place. Motivated by the complexity of planning in manufacturing companies, this thesis studies and develops quantitative tools to help planners in the replenishment, production and delivery planning processes. From this perspective, realistic models and efficient methods are proposed to support decision making in industrial companies, mainly in small- and medium-sized enterprises (SMEs). The contributions of this thesis represent a scientific breakthrough based on a comprehensive literature review about replenishment, production and distribution planning that helps to understand the main models and algorithms used to solve these plans, and highlights trends and future research directions. It also provides a holistic framework to characterise models and algorithms by focusing on production planning, scheduling and sequencing. This thesis also proposes a decision support tool for selecting an algorithm or solution method to solve concrete replenishment, production and distribution planning problems according to their complexity, which allows planners to not duplicate efforts modelling or programming solution techniques. Finally, new state-of-the-art mathematical models and solution approaches are developed, such as matheuristic algorithms, which combine mathematical programming and metaheuristic techniques. The new models and algorithms comprise improvements in computational performance terms, and include realistic features of real-world problems faced by manufacturing companies. The mathematical models have been validated with a case of an important company in the automotive sector in Spain, which allowed to evaluate the practical relevance of these novel models using large instances, similarly to those existing in the company under study. In addition, the matheuristic algorithms have been tested using free and open-source tools. This also helps to contribute to the practice of operations research, and provides insight into how to deploy these solution methods and the computational time and gap performance that can be obtained by using free or open-source software.This work would not have been possible without the following funding sources: Conselleria de Educación, Investigación, Cultura y Deporte, Generalitat Valenciana for hiring predoctoral research staff with Grant (ACIF/2018/170) and the European Social Fund with the Grant Operational Programme of FSE 2014-2020. Conselleria de Educación, Investigación, Cultura y Deporte, Generalitat Valenciana for predoctoral contract students to stay in research centers outside the research centers outside the Valencian Community (BEFPI/2021/040) and the European Social Fund.Guzmán Ortiz, BE. (2022). Models and Algorithms for the Optimisation of Replenishment, Production and Distribution Plans in Industrial Enterprises [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/187461Compendi

Proceedings of Abstracts Engineering and Computer Science Research Conference 2019

© 2019 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Note: Keynote: Fluorescence visualisation to evaluate effectiveness of personal protective equipment for infection control is © 2019 Crown copyright and so is licensed under the Open Government Licence v3.0. Under this licence users are permitted to copy, publish, distribute and transmit the Information; adapt the Information; exploit the Information commercially and non-commercially for example, by combining it with other Information, or by including it in your own product or application. Where you do any of the above you must acknowledge the source of the Information in your product or application by including or linking to any attribution statement specified by the Information Provider(s) and, where possible, provide a link to this licence: http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3/This book is the record of abstracts submitted and accepted for presentation at the Inaugural Engineering and Computer Science Research Conference held 17th April 2019 at the University of Hertfordshire, Hatfield, UK. This conference is a local event aiming at bringing together the research students, staff and eminent external guests to celebrate Engineering and Computer Science Research at the University of Hertfordshire. The ECS Research Conference aims to showcase the broad landscape of research taking place in the School of Engineering and Computer Science. The 2019 conference was articulated around three topical cross-disciplinary themes: Make and Preserve the Future; Connect the People and Cities; and Protect and Care

Simulated Annealing

The book contains 15 chapters presenting recent contributions of top researchers working with Simulated Annealing (SA). Although it represents a small sample of the research activity on SA, the book will certainly serve as a valuable tool for researchers interested in getting involved in this multidisciplinary field. In fact, one of the salient features is that the book is highly multidisciplinary in terms of application areas since it assembles experts from the fields of Biology, Telecommunications, Geology, Electronics and Medicine

Improvements on the bees algorithm for continuous optimisation problems

This work focuses on the improvements of the Bees Algorithm in order to enhance the algorithm’s performance especially in terms of convergence rate. For the first enhancement, a pseudo-gradient Bees Algorithm (PG-BA) compares the fitness as well as the position of previous and current bees so that the best bees in each patch are appropriately guided towards a better search direction after each consecutive cycle. This method eliminates the need to differentiate the objective function which is unlike the typical gradient search method. The improved algorithm is subjected to several numerical benchmark test functions as well as the training of neural network. The results from the experiments are then compared to the standard variant of the Bees Algorithm and other swarm intelligence procedures. The data analysis generally confirmed that the PG-BA is effective at speeding up the convergence time to optimum. Next, an approach to avoid the formation of overlapping patches is proposed. The Patch Overlap Avoidance Bees Algorithm (POA-BA) is designed to avoid redundancy in search area especially if the site is deemed unprofitable. This method is quite similar to Tabu Search (TS) with the POA-BA forbids the exact exploitation of previously visited solutions along with their corresponding neighbourhood. Patches are not allowed to intersect not just in the next generation but also in the current cycle. This reduces the number of patches materialise in the same peak (maximisation) or valley (minimisation) which ensures a thorough search of the problem landscape as bees are distributed around the scaled down area. The same benchmark problems as PG-BA were applied against this modified strategy to a reasonable success. Finally, the Bees Algorithm is revised to have the capability of locating all of the global optimum as well as the substantial local peaks in a single run. These multi-solutions of comparable fitness offers some alternatives for the decision makers to choose from. The patches are formed only if the bees are the fittest from different peaks by using a hill-valley mechanism in this so called Extended Bees Algorithm (EBA). This permits the maintenance of diversified solutions throughout the search process in addition to minimising the chances of getting trap. This version is proven beneficial when tested with numerous multimodal optimisation problems