Dissertationen zum Thema „Production line optimization“

This project is a continuous research of a topic well-known in the literature, namely, the performance study of unbalanced unpaced production system. In the literature, there were many studies that investigated the statistical outputs of an unbalanced production line using simulation. This project focuses on researching the outputs like average buffer level and idle time that are rarely studied in previous research by using optimization tools from discrete event simulation software FACTS.The models used in the article (Shaaban & McNamara, 2009) have been used as a guideline during the development of the simulation models for this project. Two simulation models were created, each using different discrete event simulation software, namely FACTS analyzer and Plant simulation. Those simulation models fulfills its role in verification & validation stage, with their statistical outputs compared to each other and with Shaaban and McNamara’s results. After verification & validation comes optimization of those simulation models, by using optimization tools from FACTS.The research area expanded during the optimization phase. Originally Shaaban et.al analyzed unbalanced production line with one fixed value of coefficient of variation. In order to expand the view on the properties of an unbalanced production line, three more coefficient variation were added with total of four in this project. As a result, 12 optimization results were created at the end of this project. Each optimization has 30 000 iterations to ensure its convergence.The first step of analysis is done by locating all Pareto-optimal solutions with optimization tools in FACTS. The raw data of all solutions are later transferred and converted into EXCEL files. Using scatter graph and putting all outputs against each other in EXCEL, it creates visual graph that can be used to analyze and to investigate interesting behavior in an unbalanced production line.The analysis on the optimization results showed several interesting behaviors from production line with different settings. One being that if a production line possess worse coefficient of variation than its competition. By raising the inter-stage buffer level of the production line with inferior coefficient of variation, it can achieve the same level, if not greater outputs than its competitor who possess better coefficient of variation. The other interesting behavior are optimization results with highest outputs in regard of either idle time or average buffer level, with deep analyzation using optimization tools from FACTS. Certain operation time pattern and inter-stage buffer pattern could be observed from those results.

This study examines the automatization potential for two production lines at Scania Transmission workshop in Södertälje using Industry 4.0 technologies. In order to do so, the capabilities of the operational performance and safety features of cobots and an Automated Visual Inspection System is theoretically investigated and intended to substitute CNC operators on certain tasks such as loading of conveyors and quality controls. The purpose of the study is to generate a realistic approach and give insight to the benefits of a future practical implementation.Previous research around these technologies as well as the actual data recordings and several interviews that took place during on-site visits is presented. The results show that a significant amount of time can be saved and allocated differently. Based on the findings of the study, a layout for the cobots and AVIS placement is proposed, aiming for CNC operator’s better control over the critical parts of the production lines, thus contributing to a much more manageable workflow.

At ABB’s high voltage cable factory in Karlskrona, there is a line production that is regarded as a bottleneck. The production rate at this workplace as well as the large variations of setups has created two major problems. The first problem is that it has become difficult for the planning department to determine the lead times for delivery to the customers. The other problem is that the long setup times has made this line production the bottleneck of the whole production. The factory at ABB HVC includes a number of line productions, where each line has their own purpose and value adding processes. The armoring line AR50 that this project has the focus to improve has the last value adding processes for the factory’s main product. The factory’s main product is the Cross-Linked Polyethylene cable, shortened XLPE. There are several different advantages with the XLPE-cable system. First of all they are maintenance-free and environmentally friendly. The main reason that the XLPE-cable is environmentally friendly is because it have low electrical losses. Since the submarine cables are underground the cables are invisible and not effected by weather conditions. This project implements the method SMED as well as various methods from the LEAN transcript in order to reduce the setup times and create a more stable and effficient production. An Ishikawa diagram were used in order to determine the root causes of the problems. Later both technical and management solutions were proposed and implemented. The project has concluded impressive results regarding setup time reduction and annual cost savings. It also enlightens the large potential for further improvement. This project will be continued during the year of 2014 in order to implement the proposed solutions. The future improvements are not just technical but also related to management and group dynamics.

More dynamic markets, shorter product life cycles and comprehensive variant management are challenges that dominate today's market. These maxims apply to the automotive sector, which is currently highly exposed to trade wars, changing mobility patterns and the emergence of new technologies and competitors. To meet these challenges, this thesis presents the creation of a digital twin of an existing production line of electric motors using discrete event simulation. Based on a detailed literature research, a step-by-step establishment of the simulation model of the production line using the software Plant Simulation is presented and argued. Finally, different experiments are carried out with the created model to show how a production line can be examined and optimized by means ofsimulation using different parameters. Within the scope of the different experiments regarding the number of workpiece carriers, number of operators as well as buffer sizes, the line was examined concerning the increase of the output. Furthermore, the simulation model was used to make decisions for future investments in additional XXX machines. Four different scenarios were examined and optimized. By examining the different parameters, optimization potentials of XXX% in the first scenario and up to XXX% in the fourth scenario were achieved. Finally, it was proven that the developed simulation model can be used as a tool for optimizing an existing production line and can generate useful investment information. Beyond that, the development of the simulation model can be employed to investigate further business questions at hand for the specific production line in question.
Mer dynamiska marknader, kortare produktlivscykler och omfattande varianthantering är utmaningar som dominerar dagens marknad. Dessa maximer gäller bilindustrin, som för närvarande är mycket utsatt för handelskrig, förändrade rörlighetsmönster och framväxten av ny teknik och nya konkurrenter. För att möta dessa utmaningar innebär denna avhandling skapandet av en digital tvilling av en befintlig produktionslinje av elmotorer med diskret händelsesimulering. Baserat på en detaljerad litteraturforskning presenteras och argumenteras en steg-för-steg-etablering av simuleringsmodellen för produktionslinjen med hjälp av programvaran Plant Simulation. Slutligen utförs olika experiment med den skapade modellen för att visa hur en produktionslinje kan undersökas och optimeras med hjälp av simulering med hjälp av olika parametrar. Inom ramen för de olika experimenten när det gäller antalet arbetsstyckesbärare, antalet operatörer samt buffertstorlekar undersöktes linjen om ökningen av produktionen. Dessutom användes simuleringsmodellen för att fatta beslut för framtida investeringar i ytterligare hårnålsmaskiner. Fyra olika scenarier undersöktes och optimerades. Genom att undersöka de olika parametrarna uppnåddes optimeringspotentialer på XXX % i det första scenariot och upp till XXX % i det fjärde scenariot. Slutligen bevisades det att den utvecklade simuleringsmodellen kan användas som ett verktyg för att optimera en befintlig produktionslinje och kan generera användbar investeringsinformation. Utöver detta kan utvecklingen av simuleringsmodellen användas för att undersöka ytterligare affärsfrågor till hands för den specifika produktionslinjen i fråga.

Motivated by operational issues in real-world glass manufacturing, this thesis addresses a problem of laying out and sequencing the orders so as to minimize wasted glass, called scrap. This optimization problem combines aspects of traditional cutting problems and traditional scheduling and sequencing problems. In so far as we know, the combination of cutting and scheduling has not been modeled, or solved. We propose a two-phase approach: snap construction and constructing cutting and offload schedules. Regarding the second phase problem, we introduce FGSP (float glass scheduling problem), and provide its solution structure, called coveys. We analyze simple sub-models of FGSP considering the main elements: time, unit, and width. For each model, we provide either a polynomial time algorithm or a proof of NP-completeness. Since FGSP is NP-complete, we propose a heuristic algorithm, Longest Unit First (LUF), and analyze the worst case performance of the algorithm in terms of the quality of solutions; the worst case performance bound is {1+(m-1)/m}+{1/3-1/(3m)} where m is the number of machines. It is 5/3 when m=2. For the real-world problem, we propose two different methods for snap construction, and we apply two main approaches to solve cutting and offloading schedules: an MIP approach and a heuristic approach. Our solution approach produces manufacturing yields greater than 99%; current practice is about 95%. This is a significant improvement and these high-yield solutions can save millions of dollars.

Le travail présenté dans cette thèse concerne la formulation et la résolution de deux problèmes d'optimisation multi-objectifs. Ces problèmes de décision, liés à une approche holistique, ont pour but de sélectionner la meilleure configuration « produit/ligne d’assemblage » à partir d'un ensemble de design produits, et de ressources. Concernant le premier problème, un modèle de coût a été développé afin de traduire les interdépendances complexes entre la sélection d’un design produit et les caractéristiques des ressources. Une étude empirique est proposée et vise à comparer, selon plusieurs indicateurs de qualité multi-objectifs, différentes méthodes de résolution - comprenant des algorithmes génétiques, de colonies de fourmis, d’optimisation par essaims particulaires, des chauves-souris, de recherche du coucou et de pollinisation des fleurs. Plusieurs règles de dominance et une recherche locale spécifique au problème ont été appliquées aux méthodes de résolution les plus prometteuses. Concernant le second problème, qui se penche également sur le dimensionnement des stocks tampons, les méthodes de résolution sont à un modèle de simulation à événements discrets, dont la fonction première est l’évaluation des valeurs des différentes fonctions objectives. L’approche holistique associée aux deux problèmes a été validée avec deux cas industriels
The work presented in this thesis concerns the formulation and the resolution of two holistic multi-objective optimization problems associated with the selection of the best product and hybrid assembly line configuration out of a set of products, processes and resources alternatives. Regarding the first problem, a cost model was developed in order to translate the complex interdependencies between the selection of specific product designs, processes and resources characteristics. An empirical study is proposed, which aimed at comparing, according to several multi-objective quality indicators, various resolution methods – including variants of evolutionary algorithms, ant colony optimization, particle swarm optimization, bat algorithms, cuckoo search algorithms, and flower-pollination algorithms. Several dominance rules and a problem-specific local search were applied to the most promising resolution methods. Regarding the second problem, which also considers the buffer sizing, the developed algorithms were enhanced with a genetic discrete-event simulation model, whose primary function is to evaluate the value of the various objective functions. The demonstration of the associated resolution frameworks for both problems was validated through two industrial-cases

With the rapid development of computers and their proven usability in manufacturing environments, simulation-based optimisation has become a recognised tool for proposing near-optimal results related to manufacturing system design and improvement. As a world-leading manufacturer within their field, Volvo GTO in Skövde, Sweden is constantly seeking internal development and has in recent years discovered the possibilities provided by flow simulation. The main aim of this thesis is to provide an optimal buffer size of a new post-assembly and packaging line (Konpack) yet to be constructed. A by-product of the flow simulation optimisation project in form of a flow simulation process evaluation was also requested. The simulation project started with a pre-study including the development of the frame of reference and an analysis of the literature focused on merging Lean philosophy with simulation-based optimisation. The simulation model was built based on both historical and estimated data. The optimisation results showed different buffer size alternatives depending on the throughput to be achieved, these are discussed, and near-optimal solutions presented for decision-making. Additionally, four experiments were carried out, both contributing to the model’s credibility as well as providing new and valuable insight to the stakeholders. The conclusions drawn from the optimisation and experiments indicate that Konpack will be able to meet the established throughput goals, provided that the suggested near-optimal solutions are considered. The experiments also unanimously point to the fact that Konpack has a built-in overcapacity, utilizable by optimising certain suggested input parameters. Additionally, an evaluation of the completeness of the standard simulation process employed by Volvo GTO is provided, concluding that no major changes are needed. Nevertheless, there is always room for improvement. Hence, future work regarding the flow simulation process at Volvo GTO is proposed.

Generic pharmaceutical supply chains are complex, interfacing humanitarian needs, industrial manufacturing, regulatory bodies and numerous other shareholders. This report gives a brief introduction to a current supply chain process within a company as well as a proposal to improve the supply chain financially, socially and environmentally. Data has been collected mainly through interviews and literature studies in order to conduct a case study. The project included an initial business case, calculations of necessary data in order to justify the work as well as to quantify the results. The main part of the proposal is to postpone the packing of medical products to a later stage as a way of improving the triple bottom line. Theoretically, this change results in lower ordering costs, lower volumes scrapped and thus lower scrapping costs and pollution, a decrease in order volumes further reducing costs and pollution and more. The study met the intended outcomes and would theoretically improve the company in line with the set targets. At the time of writing it is yet unclear whether it will lead to any action on behalf of the company.
Försörjningskedjorna inom farmaceutisk generika är komplexa med många externa beröringspunkter såsom mänskligt behov, industriell produktion, regulatoriska organisationer och andra intressenter. Den här rapporten erbjuder en kort introduktion till den befintliga försörjningsprocessen i ett företag i branschen samt ett förslag till hur företaget kan förbättra sin försörjningskedja ur ett ekonomiskt, socialt och miljömässigt perspektiv. Information har inhämtats främst genom intervjuer och litteraturstudier som har utgjort grund för en fallstudie. Projektet inkluderade framtagning av ett beslutsunderlag, datakalkyler för att ge stöd åt syftet med arbetet samt för att kvantifiera resultaten. Huvuddelen av förslaget utgörs av senareläggningen av packningsstadiet för medicinska produkter och effekten det får på det som på engelska kallas triple bottom line. Implementeringen av projektet ska teoretiskt leda till bland annat förbättrade vinstmarginaler, lägre andel kassationer och därmed en minskning av kostnader och utsläpp hänförliga till kassationer, lägre ordervolymer vilket i sin tur leder till sänkta kostnader och utsläpp. Studien har gett ett positivt utfall relativt målsättningen och implementeringen ska teoretiskt leda till en förbättring av verksamheten i linje med de uppsatta målen. I skrivande stund är det oklart huruvida företaget kommer att implementera förslaget.

This work deals with analysis one of the production lines at ModusLink Czech Republic s.r.o. It seeks to find possibilities for automation of different processes on the line, currently performed manually. The basic focus is to find the appropriate technical solutions to the automated control of the designated production line. The work seeks to describe all meaningful solutions and compare their advantages and disadvantages. From this comparison of the final proposal is based on comprehensive solutions with the use of machine vision. Another point is the selection of a suitable contractor for the implementation of the proposal, making its advantage in economic terms and the resulting recommendations, if implemented the proposal.

Due to the changes and improvements that have occurred over the years, the manufacturing sector has evolved. Companies in the 21st-century face changes in the marketplace that are difficult to predict due to international competition and the rapid emergence of new products. To cope, companies must reinvent themselves and design manufacturing systems that seek to produce quality and low-cost products, and respond to the changes that must be faced. These capabilities are encompassed in reconfigurable manufacturing systems (RMS), capable of dealing with uncertainties quickly and economically. On the other hand, production planning with this type of system presents a significant challenge. Although simulation-based optimization techniques have been applied to address certain RMS challenges, only a few studies have applied simulation-based multi-objective optimization to simultaneously address several conflicting design objectives, as is the case in this project. This project aims to investigate some aspects using SBMO that directly affect the performance of a plant and demonstrate the usefulness of the method.

Det finns övrigt digitalt material (t.ex. film-, bild- eller ljudfiler) eller modeller/artefakter tillhörande examensarbetet som ska skickas till arkivet.

Les procédés chromatographiques multicolonnes continus se sont imposés comme technique séparative dans l’industrie pharmaceutique en raison de leur productivité élevée et de leur développement rapide. De nos jours, la modélisation, le dimensionnement et l’optimisation des procédés LMS et Varicol sont considérés comme établis. Le fonctionnement automatique optimisé et robuste de ces procédés reste cependant un sujet de recherche. Le plus souvent, les paramètres opératoires sont choisis en deçà du réglage optimal afin d’inclure une marge de robustesse. Ils sont ajustés manuellement par un opérateur expérimenté pour maintenir les produits à leurs spécifications de pureté. Le nombre élevé de séparations chromatographiques rend crucial le développement d’une application d’un contrôle avancé de ces procédés. Récemment, plusieurs méthodes de contrôle des procédés LMS ont été proposées. Ce travail de thèse présente une nouvelle approche de contrôle avancé. Cette commande ajuste les paramètres opératoires d’une séparation grâce à deux types de mesure : une mesure en ligne et une mesure hors ligne. Une validation expérimentale du schéma de contrôle a été effectuée sur un procédé Varicol. Les résultats présentés démontrent que la commande permet d’amener la pureté des produits à leurs spécifications, d’optimiser les performances du procédé et de répondre aux perturbations, tout en sécurisant la pureté du produit cible
Multicolumn continuous chromatographic processes became a key separation technology in the areas of pharmaceutical industry thanks to high productivity and short process development times. Today, modeling, design, and optimization of SMB and Varicol, are well established. However a robust and optimized operation of processes is still an open issue. The common practice is to operate processes under suboptimal operating conditions in order to gain the necessary robustness. The operating parameters are tuned manually by experienced operators in order to maintain the product specifications. Therefore, as chromatographic applications spread, process control problem becomes increasingly important. Recently, several control methodologies of SMB process have been proposed. This thesis work introduces a new advanced control system approach. This system adjusts operating parameters thanks to two kinds of measurements : an in-line measurement and an at-line measurement. The performance of this control scheme is demonstrated through several experiments on Varicol. The reported results aim to demonstrate that the controller is able to deliver the products within the specifications, to optimize the process performance and to answer to disturbances while protecting the key product

Sedan mitten av 90-talet har byggkostnaderna ökat drastiskt i Sverige samtidigt som konkurrens från utländska entreprenörer ökat vilket gör att de svenska entreprenörerna måste hitta nya lösningar för att få ner produktionskostnaderna för att vara fortsatt konkurrenskraftiga. En stor kostnadspost är slöseri i form av stillestånd och dåligt utnyttjande av resurser som är en risk kopplad till bristfällig planering. Vid vägprojekt är masshanteringen en central del och står för ca 25% av den totala kostnaden vilket gör det till en attraktiv fråga att hantera i projektet och söka alternativa lösningar och optimeringar för att få ner kostnaden. Detta examensarbete har därför inriktats mot att undersöka hur digitala projektstyrningsverktyg kan bidra med att minska kostnader och risker för entreprenörer vid schakt & fyllnadsarbeten i vägprojekt. Detta genom att införa verktyg som massoptimering baserad på linjär programmering samt tidlägesplanering i vägprojekt. För att undersöka detta har tre forskningsfrågor tagits fram   FF 1: Vilka metoder finns tillgängliga för att produktionsplanera vägprojekt och hur kan de implementeras? FF 2: Hur kan digital massoptimering och tidlägesplanering minska kostnaderna för entreprenören? FF 3: Hur kan digital massoptimering och tidlägesplanering minska riskerna för entreprenören?   För att besvara forskningsfrågorna har en litteraturstudie inom massoptimering och tidlägesplanering samt en fallstudie av ett vägprojekt i Segersta som består av en 850 meter lång ny vägsträcka samt en vägport under befintlig järnväg genomförts. Fallstudien har huvudsakligen gjorts med hjälp av dataprogrammet Dynaroad och består av tre huvudsakliga delar vilka är datainsamling, en Dynaroad-modell baserad på den ursprungliga tidplan som gjordes inför projektet samt en optimerad modell som sedan jämförs mot anbudskalkylen och den ursprungliga tidplanen.   Resultaten från fallstudien påvisar att förbättringspotential finns på en mängd punkter såsom Tidsplanering, Resursplanering, Massoptimering samt granskning av anbudskalkyl inför produktionsstart.     Fallstudien visar att kostnaden för dumprar i projektet kan minskas med ca 20% jämfört med anbudskalkylen. Kostnaden för produktionsresurser, som exempelvis grävmaskiner och vältar, kan minskas med 30% jämfört med vad den ursprungliga tidplanen hade kostat vilket motsvarar en total besparing på 12% sett till schakt & fyll-aktiviteterna i projektet. Med dagens mjukvara blir det möjligt för entreprenörer att på ett enklare sätt implementera metoder som Line of Balance & Massoptimeringar och på så vis förbättra sin produktionsplanering på ett betydligt enklare sätt än vad som varit möjligt tidigare. Genom att modellera upp en tidplan med verktyg som Line of Balance kan entreprenören snabbt se förbättringsområden såsom produktionskrockar och aktiviteter som kan behöva fler eller färre resurser. Detta ger entreprenören en större kontroll över utförandet vilket kan bidra till att produktionen håller den budget som är uppsatt i anbudskalkylen. Kombinerat med en massoptimering levererar det två starka verktyg för att förbättra dagens produktionsplanering som bör ha en central roll i framtida vägprojekt.
Since the mid-1990s, construction costs have increased drastically in Sweden, meanwhile competition from foreign entrepreneurs has increased, which means that Swedish entrepreneurs must find new solutions to lower production costs in order to remain competitive. Here unnecessary costs associated with inadequate planning emerges in the form of downtimes and poor utilization of resources. Earthwork operations in road construction, which accounts for about 25% of the total construction cost, provides opportunities for optimizations and alternative solutions to lower the construction cost. This master thesis are therefore focused on examining how digital project management tools can contribute to reducing costs and risks for contractors in cut & fill activities in road projects using mass optimization and location-based time planning methods. Three research questions have been posed:   RQ 1: What methods are available for production planning of road projects and how can they be implemented? RQ 2: How can digital mass optimization and time planning reduce the costs for the contractor? RQ 3: How can digital mass optimization and time planning reduce the risks for the contractor?   To answer the research questions, a literature study in mass optimization and time-planning has been carried out along with a case study of a road construction project in Segersta, Sweden. The case study consists of an 850-meter-long new road section and an underpass below the existing railway. The software Dynaroad have been used to plan the road construction in the case study. The case study was divided in three main steps; (1)  data collection, (2) a Dynaroad model based on the original time schedule that was made prior to the project and (3) the optimized model was then compared against the bid calculation and the original schedule.   The results of the case study show that the potential for improvement exists in a number of points, such as Time Planning, Resource Planning, Mass Optimization and examination of bid calculations prior to production start. The case study shows that the cost of dumpers in the project can be reduced by about 20% compared to the bid estimate. The cost of production resources, such as excavators and rollers, can be reduced by 30% compared to what the original timetable had cost, which corresponds to a total saving of 12% in terms of the cut & fill activities in the project. Today's software makes it possible for contractors to implement methods such as the Line of Balance & Mass optimization to improve their production planning in a much simpler way than previously possible. With Line of Balance schedules the contractor can quickly see improvement areas such as production clashes and activities that may need more or less resources. This gives the contractor greater control over the execution, which can contribute to keeping the budget set in the bid calculation. Combined with a mass optimization, it delivers two strong tools to improve today's production planning that should have a central role in the planning and execution of future road projects.

Denna studies syfte är att leverera ett förslag på hur ett tillverkande företag i Sverige kan öka sin kapacitet, sitt genomflöde och flexibilitet i en manuell produktionslina. Produktionsgolvet är trångt för de anställda på grund av stora lagernivåer intill produktionslinan. Det finns fem arbetsstationer, tre flaskhalsar i produktionen och antalet PIA (Produkter I Arbete) är högt. Studien genomför mätningar för att kartlägga nuläget, hur den aktuella layouten och prestandan ser ut. För att mäta nuläget samlar studien in data genom observationer, en processpromenad, informella intervjuer och genomför egna mätningar. Datainsamlingen analyseras med hjälp av teorier och metoder från Lean, TOC (Theory of Constrains), linjebalansering och produktionsledning. Studien använder sig av 5s som angreppssätt för att systematiskt uppnå genomgående renhet av arbetsplatsen och en standardisering av påfyllnads- och prognostiseringsprocessen. Studien finner att för att öka produktionslinans kapacitet kan bemanningen på produktionslinan ökas, med detta som utgångspungspunkt föreslås en ny layout som tillåter två extra anställda att arbeta på produktionslinan. Detta uppnås genom att dela upp nuvarande delmoment i produktionslinan och skapa två extra stationer. Detta ändrar antalet arbetsstationer från fem till sju och tillåter två extra anställda att arbeta i produktionslinan. Detta eliminerar också två mindre flaskhalsar i produktions flödet. Vidare innefattar förslaget en ny rutin för påfyllnad- och prognostiseringsprocessen som bestämmer hur många artiklar som ska lagerföras vid produktionslinan. Till sist föreslås att den nu enda flaskhalsen ska styra takten, vilket gör processen till ett dragande system styrt av efterfråga istället för ett styrt av generell tillgång. Detta innefattar också att produktionslinan ska börja tillverka ett säkerhetslager med färdiga produkter, detta säkerhetslager ska bytas ut kontinuerligt för att hindra produkterna passerar utgångsdatum. Resterande majoritet av produktionen ska endast ske mot kundorder istället för mot ett lager. För att implementera förslaget bör organisationen utbilda sig och dess anställda i teorierna studien använder sig av. Både ledning och anställda i produktionslinan måste förstå teorierna och varför de används för att implementeringen ska lyckas.
The purpose of this study is to deliver a proposition on how a Swedish manufacturing company can improve its’ capacity, flow and flexibility in a manual production line. The production floor is crowded as a result of large quantities of articles adjacent to the production line. The production line has five workstations, three bottlenecks and has a high number of WIP (Work-In-Progress). The study collects data to assess the situation, the production lines performance and how the current layout is planned. To measure the current situation the study collects data through observations, a process tour, informal interviews and conducts its own measurements. The collected data is analysed using theories and methods from lean, TOC (Theory of Constrains), line balancing and production management. The study is approaching the problems using 5s to systematically achieve pervading cleanness in the workplace and a standardisation of the refilling- and prognostication process. The study finds that to increase the capacity of the production line, the staffing can be increased. Using this as a standing point, the study proposes a new production layout that allows two extra employees to work on the production line. This is achieved by creating two additional workstations in the production line. Changing the number of stations from five to seven and allowing two extra employees to work in the production line. This layout change also eliminates two smaller bottlenecks in the production flow. Furthermore, the propositions suggest a new routine for the refilling- and prognostication process that determines how many articles to store within the production floor. Lastly the proposition suggests that the now single bottleneck in the production flow decides the production rate. Making the production line a pulling system set by the demand of the bottleneck, rather than a system set by general assets. This also includes that the production line is going to start producing safety stock of completed products, this safety stock will continuously be replaced to prevent the products from passing expiration date. The remaining majority of the production should only be done by customer order, rather than producing to store complete products. In order to implement the proposition, the organization need to educate itself and its employees, both management and workers need to understand the concepts the proposition uses and why the concepts are used in order for the implementation to be successful.

Sekretess

This work is focused on solving problems in Industry 4.0. Main part of this work describes development of a discreet simulation model based on queuing theory. This model will be used for a heuristic optimization of a production line. Model will be validated with data from real production line. Improvement of effectivity using discrete model and heuristic optimization will be shown on virtual production line.

Cette thèse contribue à l'évaluation et l'optimisation de l'ergonomie dans la phase de conception des systèmes de production. Une mauvaise ergonomie physique dans les systèmes de production se traduit par une productivité plus faible et des blessures des opérateurs, et augmente les coûts pour les entreprises. L'objectif principal de ce travail est de proposer des méthodes d'optimisation pour la conception de systèmes de production, tenant compte à la fois de l'ergonomie, de la productivité et des coûts. Ce travail se concentre sur la conception préliminaire des lignes d'assemblage. L'enjeu est de fournir aux décideurs des méthodes d'optimisation pour la prise en compte de l'ergonomie, tout en satisfaisant toutes les contraintes technologiques et économiques. Les problèmes combinatoires considérés sont les problèmes d'équilibrage de lignes d'assemblage et de sélection des équipements. Nous avons considéré un modèle quantitatif d'ergonomie basé sur des équations de fatigue et de récupération tirées de la littérature. Nous avons proposé une linéarisation permettant de définir un programme linéaire en variables entières pour ce problème et des méthodes de résolution optimale et approchée. Nous avons également proposé une généralisation de l'approche, avec un modèle multi-objectif optimisant le coût et l'ergonomie. Nous avons développé un algorithme multi-objectif pour sa résolution. Sur la base des modèles et des algorithmes d'optimisation proposés, nous avons défini une méthodologie pour la conception de lignes d'assemblage avec l'optimisation de l'ergonomie dès la phase de conception. Cette méthodologie a été appliquée avec succès dans deux cas industriels
This thesis contributes to the research stream of evaluation and optimization of ergonomics in the design phase of manufacturing systems. Poor physical ergonomics in manufacturing systems results in lower productivity, lower motivation, injuries, and increases costs for companies. The main objective of this work is the proposition of optimization methods for manufacturing systems design, with the joint consideration of ergonomics, productivity, and cost. This work focuses on the preliminary design of assembly lines. The challenge is to provide decision-makers with optimization methods to take ergonomics into account while satisfying all technological and economic constraints. The combinatorial problems considered are the assembly line balancing problem and the selection of equipment. We considered a quantitative model of ergonomics based on fatigue and recovery equations taken from the literature. In addition to the combinatorial nature of problems dealt with, the main scientific challenge stems from the non-linear nature of the ergonomics model. We proposed a linearization allowing defining an integer linear program, we developed optimal and approximate resolution approaches. Besides, we proposed a generalization of the approach, with a multi-objective model optimizing cost and ergonomics. We developed a multi-objective algorithm for its resolution.Based on the proposed models and optimization algorithms, we have defined a methodology for the design of assembly lines with the optimization of ergonomics from the design phase. This methodology has been successfully applied to industrial cases

There are manufacturing systems all over the world and all of them present dif- ferent characteristics. To get close to those manufacturing systems and aid them to analyze data and improve their efficiency, it arises FACTS Analyzer®. The present project concerns the development of a bottleneck analysis using REVERSE- SCORE (Simulation based COnstraint REmoval), feature included in FACTS Ana- lyzer. It is used Simulation-based Multi-Objective Optimization (SMO) to ana- lyze the different variables of a production line and investigate how to best extend previous application of SMO for bottleneck detection to not only consider im- provements of system parameters but also degradations of them. Degrading some system parameters can have many hidden advantages such as reduce power con- sumption, increase material efficiency or lengthen the useful life of the machines or tools, advantages that can draw near sustainability.

L'objectif de la thèse est de créer et développer de nouvelles méthodes de résolution efficaces des problèmes combinatoires en configuration des lignes de fabrication. Deux problèmes ont été particulièrement étudiés: le problème d'équilibrage et de choix d'équipement pour des lignes dédiées et le problème de minimisation des coûts de changements de séries pour des lignes multi-produits. Une solution du premier problème consiste en une affectation admissible des ressources à un nombre de stations à déterminer de sorte que le coût total soit minimal. Afin de résoudre ce problème, nous l'avons réduit au problème de partition d'ensemble et l'avons résolu par des heuristiques gloutonnes et une méthode exacte de génération de contraintes. Les expérimentations sur différentes instances ont montré que la nouvelle approche de résolution surclasse les approches antérieures de la littérature en termes de qualité de solution et de temps de calcul. Pour le second problème deux critères sont considérés lexicographiquement : la minimisation du nombre de stations et la minimisation du coût de changement de séries. Nous avons examiné successivement les cas d'exécution parallèle et séquentielle des opérations. Des solutions approchées ont été trouvées par des heuristiques gloutonnes. Ensuite, nous avons proposé deux modèles de programmation linéaire en nombres entiers (PLNE) afin de trouver le nombre de stations minimal et ensuite d'obtenir le coût de changement de séries minimal. Les résultats des expérimentations sur ces nouveaux problèmes se sont avérés prometteurs à la fois en termes de qualité de solution et de temps de calcul.

Dissertation presented to obtain a Ph.D. degree in Engineering and Technology Sciences, Systems Biology at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa
Rotavirus-like particles (RLPs), a vaccine candidate against rotavirus disease, were produced by infecting Spodoptera frugiperda Sf-9 cells with genetically engineered recombinant baculoviruses. RLPs are spherically shaped particles composed by three viral proteins (vp) of rotavirus, vp2, vp6 and vp7, arranged in a triple layered structure. A diversity of protein structures, other than the correctly assembled RLP, are observed at the end of a typical production run suggesting that the protein assembly process is rather inefficient. Contaminants such as trimers of vp6 and vp7, vp6 tube-like structures, single-layered vp2 particles, double layered particles of vp2 and vp6 or RLPs lacking one or more subunits represent almost 88% of the total mass of proteins expressed. Thus, optimal control of protein expression concomitant with efficient particle assembly are critical factors for economical RLP production in the baculovirus/insect cells system.

Aquesta tesi es centra en l'avaluació de la fermentació en estat sòlid (FES) de residus agroindustrials, com alternatiu per a la producció d'aromes de valor afegit. Dos grups de compostos han estat considerats com a objectius. Les aromes de fruita, inclosos alguns compostos volàtils com aldehids, cetones, alcohols i èsters. D'aquests, els èsters alifàtics són aquells amb més valor afegit donat el seu particular olor a fruites. El segon grup són els aromes de roses, constituïts pel 2-feniletil alcohol (2-FA) i el 2-feniletil èster (2-FE); compostos utilitzats com a additius gràcies al seu olor a roses. En tots dos casos, l'objectiu ha estat el desenvolupament de bioprocessos basats en l'ús de residus, emprant com el bagàs de canya i les melasses de remolatxa. Amb aquest objectiu, s'ha utilitzat el llevat Generalment Reconeguda com Segur Kluyveromyces marxianus. La bioproducció de les aromes de fruita s'exposen a la primera secció. Aquesta inclou la selecció del substrat, així com l'avaluació preliminar d'algunes de les variables que afecten al procés. Un cop seleccionat el substrat, la producció d'aquests compostos ha estat avaluada a escala laboratori en bioreactors de 0.5L operats en discontinu. D'aquest apartat es pot indicar que el procés es veu significativament afectat per la temperatura i el cabal d'aire. Es va trobar que la màxima producció de volàtils (incloses totes les espècies quantificades) va ser de 161 mgVol per gram de substrat inicial en base seca (gST), a 40°C, 0.14 Lh-1g-1ST i addicionant un 35% de melasses. D'altra banda, la màxima producció d'èsters va ser obtinguda a 30°C, 0.11 Lh-1g-1ST i addicionant un 25% de melasses, aconseguint-se 47 mgEstg-1ST. Finalment, partint de l'optimització del procés a escala laboratori, el procés va ser avaluat a escales superiors (4.5 i 22L). En aquest cas, l’estudi s'ha enfocat en l'efecte que tenen les estratègies d'operació sobre l'acompliment global del procés. Així, la FES en discontinu s'ha comparat amb el procés emprant barrejat intermitent i operant en fed-batch. Aquesta última estratègia ha resultat ser una eina que afecta positivament la selectivitat cap als èsters, millorant al mateix temps alguns dels índexs de rendiment que descriuen el procés. La bioproducció d'aromes de rosa per FES és el objectiu de la segona secció. Inicialment s’ha fet l'avaluació de la FES en condicions estèrils en bioreactors de 0.5L. En aquest cas, es va desenvolupar un estudi inicial sobre les variables d'operació que afecten el procés, així com de diverses estratègies per millorar la producció. Es va trobar que la producció de 2-FA i 2-FE està associada amb l'activitat microbiològica del K. marxianus, i per tant, allargar aquesta activitat resulta en un factor decisiu per millorar la producció. En aquest sentit, l'addició de fonts addicionals de carboni, o l'ús de fed-batch han resultat ser alternatives eficients per millorar la producció de 2-FA i 2-FE. Partint dels resultats a escala laboratori, el procés va ser estudiat a escales més grans (1.6 i 22L) retirant algunes de les limitacions associades als processos a aquesta escala, com el control de temperatura i l'esterilització dels substrats. L'anàlisi d'aquesta part s’ha enfocat a l'ús d'estratègies d'operació com a eines per millorar l'acompliment global del procés. Així, la fermentació en discontinu ha estat contrastada amb la FES per fed-batch i la discontinua seqüencial. En aquest cas, la producció assolida en el procés en discontinu (17 mg2-FA+2-FE per gram de substrat inicial sec) va ser millorada a l'implementar les estratègies alternatives, aconseguint-se 19.2 mg2-FA+2-FEg-1ST al cas del fed-batch. De manera global, els resultats presentats constitueixen un pas endavant en el desenvolupament de la FES com a alternativa per produir aromes com a compostos de valor afegit a partir de residus agroindustrials.
Esta tesis se centra en la evaluación de la fermentación en estado sólido (FES) de residuos agroindustriales, como alternativa para la producción de aromas de valor añadido. Dos grupos de compuestos se consideraron como objetivos a estudiar. Los aromas frutales, que incluyen algunos compuestos volátiles como aldehídos, cetonas, alcoholes y ésteres. De estos, los ésteres alifáticos se consideran los de mayor valor añadido dado el olor a frutas que proveen. El segundo, los denominados aromas de rosas, conformados por el 2-feniletil alcohol (2-FA) y el 2-feniletil éster (2-FE); compuestos empleados como aditivos dado el olor a rosas que proveen. En ambos casos, el objetivo fue el desarrollo de bioprocesos basados en el uso de residuos, empleando como materias primas el bagazo de caña y las melazas de remolacha. Con este objetivo, se utilizó la levadura Generalmente Reconocida como Segura Kluyveromyces marxianus. La bioproducción de los aromas frutales se expone en la primera sección. Esta incluye la selección del sustrato, así como la evaluación preliminar de algunas de las variables que afectan al proceso. Una vez seleccionado el sustrato, la producción de estos compuestos ha sido evaluada a escala laboratorio en bioreactores de 0.5L operados por lotes. De allí se concluye que el proceso es significativamente afectado por la temperatura y el caudal de aire. Se encontró que la máxima producción de volátiles (incluidas todas las especies cuantificadas) fue de 161 mgVol por cada gramo de sustrato inicial en base seca (gST), a 40°C, 0.14 Lh-1g-1ST y adicionando un 35% de melazas. También, la máxima producción de ésteres fue alcanzada a 30°C, 0.11 Lh-1g-1ST y 25% de melazas, con 47 mgEstg-1ST. Finalmente, partiendo de la optimización del proceso por lotes, el proceso fue evaluado en escalas superiores (4.5 y 22L). Allí, la evaluación se enfocó en el efecto que tienen las estrategias de operación sobre el desempeño global del proceso. Así, la FES por lotes se comparó ante el proceso con mezclado intermitente y operando por lotes alimentados. Esta última estrategia resultó ser una herramienta que afecta positivamente la selectividad hacia los ésteres, mejorando además los índices de desempeño que describen el proceso. La bioproducción de aromas de rosa es el objetivo de la segunda sección. Inicialmente se aprecia la evaluación de la FES en bioreactores de 0.5L. Allí, se realizó un barrido inicial sobre las variables de operación que afectan el proceso, así como de algunas estrategias para mejorar la producción. Se encontró que la producción de 2-FA y 2-FE está asociada con la actividad microbiológica del K. marxianus, con lo cual extenderla es un factor que resulta decisivo para mejorar la producción. La adición de fuentes adicionales de carbono, o el uso de una alimentación fraccionada resultaron ser eficientes para mejorar la producción. Partiendo de los resultados a escala laboratorio, el proceso fue valorado a escalas mayores (1.6 y 22L) eliminando algunas de las limitaciones asociadas al trabajo a dicha escala como el control de temperatura y la esterilización de los sustratos. El análisis de esta parte se enfocó en el uso de estrategias de operación como herramientas para mejorar el desempeño global del proceso. Allí, la fermentación por lotes se contrastó ante la FES por lotes alimentados y empleando lotes secuenciales. Así, la producción alcanzada en el proceso por lotes de 17 mg2-FA+2-FE por gramo de sustrato inicial seco fue mejorada al implementar dichas estrategias, alcanzando 19.2 mg2-FA+2-FEg-1ST en el caso de lotes alimentados y 21 mg2-FA+2-FEg-1ST en los lotes secuenciales. De modo global, los resultados presentados constituyen un paso adelante en el desarrollo de la FES como alternativa para producir estos compuestos de valor añadido a partir de residuos agroindustriales.
This thesis focuses on the use of solid-state fermentation (SSF) as an alternative approach to the bioproduction of value-added aroma compounds through the valorization of selected agro-industrial residues. Specifically, two groups of objective aroma compounds have been studied. First, the fruit-like compounds, among which could be included a set of volatile scented species such as aldehydes, ketones, alcohols and esters. From these, the straight-chain esters could be catalogued as those more appreciated due to their high fruit-like aroma profile. The second group of species studied here are the semi-volatile compounds known as rose-like compounds, which are constituted by 2-phenethyl alcohol (2-PE) and 2-phenethyl acetate (2-PEA), two value-added species widely used as additives due to the rose-like odor they provide. In both cases, the aim was to develop residue-based bioprocesses using as raw materials the agro-industrial residue sugarcane bagasse (SCB) and the industry by-product sugar beet molasses (SBM). With this aim, the Generally Recognized As Safe (GRAS) yeast Kluyveromyces marxianus was used in the study. Developments related to the bioproduction of fruit-like compounds are exposed in the first section of the thesis. They include the initial substrate screening and an initial assessment of the operational variables affecting the process. Then, the optimization of the fruit-like compounds production in a batch SSF at 0.5 L system is developed. In that sense, it was found that the bioproduction is significantly affected by operational variables like the temperature and the air flow rate. While the maximum volatile production (including all the quantified species) was 161 mgVol per gram of dry substrate (g-1TS) at 40°C, 0.14 L h-1 g-1TS and 35% SBM, the ester species were maximized at 30°C, 0.11 L h-1 g-1TS and 25% SBM up to 47 mgEst g-1TS. Finally, based on the optimization of the batch SSF at lab scale, the evaluation of the process at bench-scale was performed (4.5 and 22 L scales). In this case, the analysis has been focused on the effects of some operational strategies named intermittent mixing and fed-batch SSF in the global performance of the bioprocess. Fed-batch has shown interesting characteristics affecting the selectivity of the ester species and also improving some of the evaluated performance indices. Bioproduction of the rose-like compounds via SSF is the core of the second section of this thesis. In this case, the first part is devoted to the evaluation of the feasibility of the process under sterile conditions in a batch SSF 0.5 L system. It was found that extending the K. marxianus activity is a key factor to increase the 2-PE and 2-PEA production. In this sense, by adding supplementary carbon sources to the media or splitting the substrate load (as a manner of a fed-batch mode) resulted in efficient and consistent ways to promote the biotransformation of these compounds. Based on the results at 0.5 L, the process was further evaluated at bench-scale (1.6 and 22 L scales) by releasing some of the constraints found at lab-scale such as the temperature control and the sterilization of the substrates. Again, the analysis was focused on the assessment of the operational strategies fed-batch and sequential-batch as alternative approaches to enhance the global behavior of the process. Here, strategies have succeeded increasing the 2-PE and 2-PEA production from 17 mg2-PE+2-PEA per gram of dry substrate (g-1TS) in a batch scenario, up to 19.2 mg2-PE+2-PEA g-1TS by using a fed-batch approach, and until 21 mg2-PE+2-PEA g-1TS through a sequential-batch. Overall, the results exposed in this thesis represent a step forward in the development of SSF as an alternative approach for producing valuable aroma compounds from agro-industrial wastes.

New food innovation is largely based on consumer demand, and currently many consumers demand healthy foods with clean label ingredient statements and plant-based origins. Sprouted grain products meet these qualifications and thus are growing in popularity. Sweetened products have been made from oats by adding exogenous amylase enzymes to hydrolyze starch into sugars. The purpose of this study was to create a clean label oat sweetener using endogenous enzymes. First, amylase activity under various sprouting conditions was determined for 4 hulless and 10 in-hull oat varieties. Paul (hulless variety) and Horsepower (in-hull variety) had the highest amylase activity after sprouting 120 h at 16°C. The amylase activity in these two varieties was then further optimized by determining the highest amylase activity occurred by sprouting for 120 hours at 24°C. Second, amylase activity was determined for these two varieties after oven-drying and freeze-drying of sprouted oats, followed by a 4-week ambient storage period. Paul decreased in alpha-amylase activity for both oven-dried and freeze-dried samples, whereas Horsepower remained constant in its amylase activity for oven-dried and freeze-dried samples. Stored samples were also analyzed for susceptibility to lipid oxidation using SPME-GC-MS. All hexanal levels rose during the 4-week storage study except for the oven-dried Paul samples which began high and decreased over time. Third, a slurry of sprouted Horsepower oats, oat flour, and water was incubated at 45, 55, and 65°C to determine the optimal temperature needed to create a sweetened paste for use in oat-based food products. Incubation at 55°C had the highest initial rate of sugar production as measured by normal phase HPLC. Amount of sugar produced increased over time and plateaued at 6 h.

The world becomes more integrated and sophisticated, especially in the birth of advanced technologies, which have influenced all life aspects. Automated systems could be considered an example of those aspects, which have been affected by recent changes in today’s life. The competition in the market is putting increasing pressure on different manufacturing organizations to find the best methods that enable them to stay up to date with the latest technologies in the industrial field. One of the most famous dilemmas that exist in this field is designing an efficient and flexible material handling system. This issue draws the attention of both decision-makers in different companies and software developers who put considerable effort into making that desired system real. Inclusive research needs to be performed to obtain such a system, and the most significant part of the research that requires special attention is the applied methodology.The approach to be adapted determines the degree of stability of a particular material handling system to function effectively in the case studied. Several methods are available and could be implemented to design that effective system such as meta-heuristic algorithms, and approaches that depend on simulation software tools. The latter approach, which is the simulation approach, seems to get increasing attention from developers of the industrial system since it plays a vital role in reducing the cost and preserving available resources. Besides, it helps predict future changes and scenarios of the system to be analyzed.In this project, a discrete-event simulation model was built for the proposed layout of the main shop floor owned by a Swedish manufacturing company. The corporation located in the south of Sweden, and it produces a vast range of manufacture of goods. The chosen methodology is a combination of lean, simulation, and optimization approaches. It has been implemented on the proposed layout in which material is handled into production lines by using automated guided vehicles (AGVs) as a means of transportation. The analysis of results shows potential benefits, where the production process became more efficient and organized since the operational cost has been reduced by decreasing the number of required vehicles. Moreover, the simulation approach facilitated testing new ideas and designing improved scenarios without the necessity to change the current state of the factory layout or disturbing the regular activities.

La presente tesi inizia con un’analisi dell’aspetto nutrizionale degli alimenti. In particolare, è stato discusso il concetto di dieta equilibrata, con riferimento ai principi della “dieta mediterranea”. Proprio da questo modello alimentare trae ispirazione la “ottimazione”, una tecnica sviluppata e utilizzata per programmare pasti conformi a specifici standard nutrizionali (15/30/55 tra proteine, lipidi e carboidrati sull’apporto energetico totale, proporzioni tipicamente mediterranee). Tali preparazioni alimentari sono state testate anche attraverso metodi di analisi sensoriale. Il passaggio successivo è stato l’estensione del concetto di “ottimizzazione nutrizionale” a quello di “ottimizzazione ambientale”, dovuto all’ipotizzato minor impatto ambientale della dieta mediterranea. Il LCA (Life Cycle Assessment) è la tecnica che è stata utilizzata per valutare l’impatto ambientale di alcuni prodotti alimentari, quali verdure surgelate, un salume e un formaggio. Un ulteriore passaggio è stata la creazione di uno strumento di comunicazione, una nuova etichetta ambientale, realizzata per essere utilizzata dalle aziende per comunicare le loro performance ambientali e quindi il loro impegno al miglioramento continuo, e dai consumatori per ottenere maggiori informazioni sull’impatto ambientale dei prodotti acquistati quotidianamente, al fine di accrescere il proprio senso critico ed effettuare acquisti consapevoli.
The thesis begins with an analysis of the nutritional aspects of foods. In particular, the concept of balanced diet has been discussed, by referring to the principles of "mediterranean diet". Just from this food model, the “optimation” draws inspiration, a technique developed and used to plan meals consistent with specific nutritional standards (15/30/55 between protein, fat and carbohydrate on the total energy intake, typically Mediterranean). These food preparations have been tested through sensory analysis methods. The next step is the extension of "nutritional optimization" concept to the "environmental optimization” one, owing to the presumed lower environmental impact of the Mediterranean diet. LCA (Life Cycle Assessment) is the technique used to assess the environmental impact of various food products, such as frozen vegetables, cured meats, dairy products. A further step is the creation of a communication tool, a new environmental label, designed to be used by companies to communicate their environmental performance and therefore their commitment to continuous improvement, and by consumers to obtain more information on the environmental impact of the foods daily consumed, in order to increase their critical sense and make purchases in a conscious way.

Les virus-like particles (VLPs) han sorgit com a una alternativa a les vacunes convencionals basades en virus atenuats o inactivats. La seva capacitat d’autoacoblament en base a l’expressió d’una proteïna matriu i l’absència de material genòmic d’origen víric les fa candidats atractius per a una multitud d’aplicacions. Les VLPs de Gag del virus de la immunodeficiència humana (VIH) són un tipus de VLPs amb envolta que han atret especial interès degut a les seves propietats estructurals, amb aplicacions en teràpia gènica, nanotecnologia i el desenvolupament de vacunes multivalents. Les línies cel·lulars d’insecte són un sistema de referència per a produir aquest tipus de nanopartícules ja que proporcionen les condicions adients per la seva producció i assemblatge. En aquesta tesi s’ha avaluat la producció de VLPs del VIH-1 en les línies d’insecte Sf9 i High Five amb el sistema d’expressió baculovirus i transfecció transitòria. Per tal d’assolir aquest objectiu, s’ha emprat una aproximació basada en l’ús combinat de metodologies de disseny d’experiments i funcions de resposta combinada. Paral·lelament, s’han incorporat una sèrie de tècniques de mesura per tal de monitoritzar i quantificar el procés productiu i per a la caracterització final de les VLPs. En el primer capítol s’analitzen les característiques d’ambdues línies cel·lulars d’insecte com a plataformes per a la producció de VLPs de GageGFP amb el sistema d’expressió baculovirus. En tots dos casos, l’observació de les VLPs per microscòpia electrònica de criogènia permet determinar que tenen una mida similar i també permet detectar la presència d’altres poblacions de nanopartícules. L’anàlisi dels nivells de producció de baculovirus resulta en un increment de 23 vegades de virus infectius en les cèl·lules Sf9 mentre que una proporció més gran de virus d’oclusió s’observa en les cèl·lules High Five. La presència d’aquest últim fenotip de baculovirus evidencia un canvi en la complexitat de la línia cel·lular High Five després de la infecció amb el baculovirus. Finalment, la combinació de les tècniques d’ultracentrifugació i virometria de flux mostra que les VLPs derivades de High Five tenen un major coeficient de sedimentació, la qual cosa indica que aquestes VLPs poden estar associades amb altres elements cel·lulars. Al segon capítol es determinen les condicions òptimes per a la producció de VLPs en les cèl·lules Sf9 i High Five amb el sistema d’expressió baculovirus. En aquest sentit, s’apliquen metodologies de disseny d’experiments i funcions d’optimització amb tècniques de quantificació directa de nanopartícules per tal d’aprofundir en aquests sistemes. Inicialment s’aborden dues situacions objectiu, la primera cercant la maximització de la concentració de VLPs (Quantitat) i la segona buscant un balanç entre producció i percentatge de VLPs amb estructura completa (Qualitat). Los niveles de producción final de VLPs en la condición de calidad son 4.5 veces más elevados para las células Sf9 mientras que en la condición de cantidad se obtienen concentraciones de VLPs similares para ambas líneas. Al tercer capítol de la tesi es desenvolupa una estratègia de producció lliure de baculovirus i basada en la transfecció transitòria de ADN plasmídic amb polietilenimina (PEI). Anàlogament al capítol 2, s’implementa una aproximació sistemàtica de disseny d’experiments i funcions d’optimització. En ambdós casos, el recanvi de medi abans de la transfecció resulta ser beneficiós per tal d’assolir els nivells més alts d’expressió. Les condicions òptimes de concentració de cèl·lules viables, ADN i PEI es determinen en aquest estudi i la formació correcta de les VLPs produïdes es corrobora per microscòpia electrònica de criogènia. En aquest cas, les cèl·lules Sf9 assoleixen un increment de 8.4 vegades en la producció de VLPs respecte a la línia cel·lular High Five. A l’últim capítol de la tesi es desenvolupen conjunts de cèl·lules Sf9 i High Five amb expressió estable i contínua de VLPs al llarg del temps. Aquests conjunts de cèl·lules d’expressió estable es generen a partir de la integració aleatòria d’ADN codificant al genoma de les cèl·lules, i les que són més productives se seleccionen per citometria en base a la seva fluorescència. En relació a la producció de VLPs, s’aconsegueix un increment de 3.7 vegades en les cèl·lules High Five respecte les Sf9. Finalment, l’estabilitat d’aquests grups cel·lulars d’expressió estable es corrobora al llarg d’un mes en cultiu.
Las virus-like particles (VLPs) han surgido como a una alternativa a las vacunes convencionales basadas en virus atenuados o inactivados. Su capacidad de autoensamblaje en base a la expresión de una proteína matriz y la ausencia de material genómico de origen vírico las hace candidatos atractivos para una multitud de aplicaciones. Las VLPs de Gag del virus de la inmunodeficiencia humana (VIH) son un tipo de VLPs con envuelta que ha suscitado especial interés debido a sus propiedades estructurales, con aplicaciones en terapia génica, nanotecnologia y el desarrollo de vacunas multivalentes. Las líneas celulares de insecto son un sistema de referencia para producir este tipo de nanopartículas puesto que proporcionan les condiciones adecuadas para su producción y ensamblaje. En esta tesis se ha evaluado la producción de VLPs del VIH-1 en las líneas de insecto Sf9 y High Five con el sistema de expresión baculovirus y transfección transitoria. Para conseguir este objetivo, se ha utilizado una aproximación basada en el uso combinado de metodologías de diseño de experimentos y funciones de respuesta combinada. Paralelamente, se han incorporado una serie de técnicas de medición para monitorizar y cuantificar el proceso productivo y para la caracterización final de las VLPs. En el primer capítulo se analizan las características de ambas líneas celulares de insecto como plataformas para la producción de VLPs de GageGFP con el sistema de expresión baculovirus. En ambos casos, la observación de las VLPs mediante microscopia electrónica de criogenia permite determinar que tienen un tamaño similar y también permite detectar la presencia de otras poblaciones de nanopartículas. El análisis de los niveles de producción de baculovirus resulta en un incremento de 23 veces de virus infectivos en las células Sf9 mientras que una proporción más gran de virus de oclusión se observa en las células High Five. La presencia de este último fenotipo de baculovirus evidencia un cambio en la complejidad de la línea celular High Five después de la infección con el baculovirus. Finalmente, la combinación de les técnicas de ultracentrifugación y virometría de flujo muestran que las VLPs derivadas de High Five tienen un mayor coeficiente de sedimentación, lo que indica que éstas pueden estar asociadas con otros elementos celulares. En el segundo capítulo se determinan las condiciones óptimas para la producción de VLPs en las células Sf9 y High Five con el sistema de expresión baculovirus. En este sentido, se aplican metodologías de diseño de experimentos y funciones de optimización con técnicas de cuantificación directa de nanopartículas para profundizar en estos sistemas. Inicialmente se consideran dos situaciones objetivo, la primera investiga la maximización de la concentración de VLPs (Cantidad) y la segunda busca un balance entre producción y porcentaje de VLPs ensambladas (Calidad). Los niveles de producción final de VLPs en la condición de calidad son 4.5 veces más elevados para las células Sf9 mientras que en la condición de cantidad se obtienen concentraciones de VLPs similares para ambas líneas. En el tercer capítulo de la tesis se desarrolla una estrategia de producción libre de baculovirus y basada en la transfección transitoria de ADN plasmídico con polietilenimina (PEI). Análogamente al capítulo 2, se implementa una aproximación sistemática de diseño de experimentos y funciones de optimización. En ambos casos, el recambio de medio previo a la transfección resulta ser beneficioso para conseguir los niveles más altos de expresión. Las condiciones óptimas de concentración de células viables, ADN y PEI se determinan en este estudio y la formación correcta de las VLPs producidas se corrobora por microscopia electrónica de criogenia. En este caso, las células Sf9 consiguen un incremento de 8.4 veces en la producción de VLPs respecto a la línea celular High Five. En el último capítulo de la tesis se desarrollan grupos de células Sf9 y High Five con expresión estable y continua de VLPs a lo largo del tiempo. Estos conjuntos celulares de expresión estable se generan a partir de la integración aleatoria de ADN codificante en el genoma de las células, y las que son más productivas se seleccionan por citometría en base a su fluorescencia. En cuanto a la producción de VLPs, se consigue un incremento de 3.7 veces en las células High Five respecto a las Sf9. Finalmente, la estabilidad de estos grupos celulares de expresión estable se corrobora a lo largo de un mes en cultivo.
Virus-like particles (VLPs) have emerged as an interesting alternative to conventional vaccines based on live-attenuated or inactivated viruses. Their capacity for self-assembling upon expression of the core protein and the lack of viral genomic material make them excellent candidates for a variety of purposes. Gag VLPs from the human immunodeficiency virus (HIV) are a type of enveloped VLPs that have drawn special attention due to their structural properties with applications in gene therapy, nanobiotechnology and multivalent vaccine development. Insect cell lines are a reference system to produce these types of nanoparticles since they provide the ideal conditions for their production and assembly. In this work, the production of HIV-1 GageGFP VLPs is assessed in Sf9 and High Five insect cells with the baculovirus expression vector system (BEVS) and transient gene expression (TGE). A rational approach based on the combination of Design of Experiments (DoE) and desirability functions is used to optimize the VLP production conditions. Advanced measurement techniques are implemented to monitor and quantify the production process and for final VLP characterization. In the first chapter, the characteristics of both insect cell lines as platforms for GageGFP VLP production with the BEVS are analyzed. In both cases, similar VLP sizes for both cells are measured by cryogenic electron microscopy (cryo-EM) and other nanoparticle populations are identified. The analysis of baculovirus production levels results in a 23-fold increase of budded virus in Sf9 cells while a larger amount of occlusion-derived virus is detected in High Five cells. The presence of this baculovirus phenotype evidences a shift in the cellular complexity of High Five cells upon baculovirus infection. Finally, the combination of analytical ultracentrifugation with flow virometry reveals a higher sedimentation coefficient for High Five-derived VLPs, indicating their possible association with other cellular compounds. In the second chapter, the optimal conditions for VLP production in Sf9 and High Five cells with the BEVS are determined by means of DoE and desirability functions. Different methodologies based on direct nanoparticle quantification are used to gain insight into these systems. Two objective situations are defined, one targeting the maximization of the VLP titer (Quantity) and the second one aiming to find a balance between production and assembled VLPs (Quality). Final VLP production levels in the quality condition are 4.5-fold higher for Sf9 cells while similar VLP concentrations are found for both insect cells in the quantity condition. In the third chapter of this thesis, a baculovirus-free VLP production strategy is optimized for both insect cells based on plasmid-mediated TGE with polyethylenimine (PEI). As in chapter 2, a systematic approach combining DoE and desirability functions is implemented. In both cases, medium exchange before transfection proves to be beneficial to achieve the highest transgene expression yields. Then, the optimal conditions for viable cell concentration at transfection, DNA and PEI concentrations are determined and the correct formation of the VLPs produced is corroborated using cryo-EM. In this case, Sf9 cells achieve a 8.4-fold increase in VLP production compared to High Five cells. In the last chapter, stable Sf9 and High Five cell pools to produce VLPs are developed by random integration and selection of the high producer cells using fluorescence-activated cell sorting. In terms of VLP production, a 3.7-fold increase in VLP titer is achieved in High Five over Sf9 stable pools. Finally, cell pool stability is successfully corroborated during the course of a month.

Includes abstract.
Includes bibliographical references (leaves 139-148).
The devastating effect the HIV pandemic has had on the human population in the last twenty five years has highlighted the great need to develop a prophylactic HIV vaccine. The manufacture of a vaccine has proven difficult though, with a number of successful designs in animal models having little success in humans. In view of this, there has been a need for novel vaccine approaches that are able to elicit effective cellular and humoral immune responses, both of which are believed to be important in the eradication of the virus. One such approach is the use of HIV-1 Gag VLPs as vaccine candidates. In this study, the production of two chimaeric (Gag VLP vaccine candidates (GagRT and GagTN) was optimized in insect cells, and their ability to enhance a murine immune response in a DNA prime-VLP boost vaccine strategy was evaluated.

This thesis presents a technique for the optimal synthesis of planar five-link mechanisms that produce a desired mechanical advantage function over a specified path. Since a five-bar linkage has two degrees of freedom, small deviations from the specified path are possible without significantly altering the mechanical advantage function. The research shows one potential application, the design of strength machines, where it is important to control force while allowing the user freedom of motion. In the past, closed-form analytical synthesis techniques have been used to design mechanical-advantage-generating linkages. This method is time consuming and case specific. However, optimal synthesis techniques apply to the general case and present a robust solution procedure. This thesis uses the non-linear pattern search technique of Hooke and Jeeves to synthesize five-bar linkages. The search technique matches user strength curves and mechanism resistance curves to produce a five-link mechanism. This mechanism produces the desired mechanical-advantage function and serves as the basis for strength training machines. Unlike analytical synthesis, optimization allows direct incorporation of a greater number of design constraints, thus resulting in solutions that are more practical. The pattern search technique aims to minimize a given objective function that depends primarily on the force generating capabilities and kinematic constraints on of the linkage.
Master of Science

A company's decisions on how to manage its reverse supply chain (RSC) are important for both economic and environmental reasons. From a strategic standpoint, the key decision a manufacturer makes is whether or not to collect products at their end-of-life (EOL) (i.e., when their useful lives are over), and if so, how to recover value from the recovered products. We call this decision as the EOL option of a product, and it determines how the RSC is designed and managed overall. Many EOL options exist for a product such as resale, refurbishment, remanufacturing and part salvage. However, many factors influence the optimal EOL option. These factors include the product's: (i) characteristics, (ii) design, and (iii) pricing. A product's characteristics are its properties that impact the various costs incurred during its production, residual part values, and customer demand. In this work, the product design is viewed as the choice of quality for each of its parts. A part's quality-level determines, among other things, its cost, salvage value, and the likelihood of obtaining it in good condition from a disassembled used product. Finally, the manufacturer must determine how to price its new and used products. This decision depends on many considerations such as whether new and used products compete and whether competition exists from other manufacturers. The choice of appropriate EOL options for products constitutes a foundation of RSC design. In this work, we study how to optimally determine a product's optimal EOL option and consider the impact of product design and product pricing on this decision. We present a full description of the system that details the relationships among all entities. The system description reveals the use of a production planning type of modeling strategy. Additionally, a comprehensive and general mathematical model is presented that takes into consideration multi-period planning and product inventory. A unique aspect of our model over previous production planning models for RSC is that we consider the product returns as being endogenous variables rather than them being exogenous. This model forms the basis of our research, and we use its special cases in our analysis. To begin our analysis of the problem, we study the case in which the product design and price are fixed. Both non-mandated and mandated collection are considered. Our analysis focuses on a special case of the problem involving two stages: in the first stage, new products are produced, and in the second stage, the EOL products are collected for value recovery. For fixed product design and price, our analysis reveals a fundamental mapping of product characteristics onto optimal EOL options. It is germane to our understanding of the problem in general since a multi-period problem is separable into multiple two-stage problems. Necessary and sufficient optimality conditions are also presented for each possible solution of this two-stage problem. For the two-part problem, a graphical mapping of product characteristics onto optimal EOL options is also presented, which reveals how EOL options vary with product characteristics. Additionally, we study the case of product design under mandated collection, as encountered in product leasing. We assume new production cost, part replacement cost, and part salvage value to be functions of the quality-level of a part along with the likelihood of recovering a good-part from a returned product. These are reasonable assumptions for leased products since the customer is paying for the usage of the product over a fixed contract period. In this case, the two-stage model can still be used to gain insights. For the two-part problem, a method for mapping part yields onto optimal EOL options is presented. Closed-form optimality conditions for joint determination of part yields and EOL options are not generally attainable for the two-stage case; however, computationally efficient methods for this problem are developed for some relatively non-restrictive special cases. It is found that, typically, a part may belong to one of three major categories: (i) it is of low quality and will need to be replaced to perform remanufacturing, (ii) it is of high quality and its surplus will be salvaged, or (iii) it is of moderate quality and just enough of its amount is collected to meet remanufactured product demand. Finally, we consider the problem of determining optimal prices for new and remanufactured products under non-mandated manufacturer's choice of collection. New and remanufactured products may or may not compete, depending on market conditions. Additionally, we assume the manufacturer to have a monopoly on the product. Again, the two-stage problem is used and efficient solution methods are developed. Efficient solution methods and key insights are presented.
Ph. D.

El planeamiento urbano empieza a estar fuertemente focalizado en la provisión de redes adecuadas de infraestructuras que estimulen el desarrollo de una movilidad sostenible. Sin embargo, la integración de criterios ambientales en el diseño y gestión de las infraestructuras necesarias para el sustento de la movilidad urbana es mínima. Teniendo en cuenta la enorme extensión y la creciente inversión global en el despliegue de nuevas infraestructuras urbanas para el sustento de la movilidad sostenible, la carga ambiental aportada al espacio público de las ciudades puede ser significativa. Esta tesis doctoral se centra en la caracterización del comportamiento ambiental del ciclo de vida de diseños convencionales de aceras de hormigón, asfalto y granito e instalaciones para la recarga de vehículos eléctricos de dos ruedas. Las aceras son pavimentos urbanos básicos implementados para el sustento de la actividad peatonal y ciclista como los modos de movilidad urbana más limpios. A su vez, las aceras son la matriz sobre la cual se distribuye un abanico diverso de elementos urbanos relacionados con el soporte de la movilidad sostenible. Las instalaciones para la recarga de vehículos eléctricos son un elemento urbano que se está implementando masivamente en las ciudades para promover la electrificación del parque de vehículos urbanos como una estrategia prometedora para reducir significativamente el consumo de petróleo y las emisiones contaminantes de la movilidad motorizada. A través de la aplicación de la metodología de Análisis del Ciclo de Vida se identifican los diseños ambientalmente más óptimos para reducir la carga ambiental aportada al espacio público y contribuir a incrementar el valor ambiental de promover la movilidad sostenible en las ciudades. Asimismo, la tesis busca identificar soluciones para mejorar el comportamiento ambiental de aquellos elementos que presentan un alto impacto con el fin de incrementar las ventajas ambientales alcanzadas en la escala urbana. Por un lado, se analiza desde una perspectiva de Ecología Industrial el potencial de producción limpia de losas de granito utilizadas en construcción. Por otro lado, se aplican principios de ecodiseño en la conceptualización de una eco-pergola (mobiliario urbano) que puede contribuir a sustentar una movilidad urbana multimodal (peatonal y bicicleta eléctrica). Como resultado del desarrollo de la tesis doctoral, se proveen inventarios completos y desagregados de los recursos movilizados (energía, agua y materiales) e impactos ambientales asociados a cada elemento objeto de estudio, se identifican puntos críticos y se definen una serie de criterios y buenas prácticas para la toma de decisiones que conlleven a optimizar el comportamiento del espacio público de las ciudades.
Urban planning starts to be heavily focused on the provision of adequate networks of urban infrastructures to stimulate a shift towards sustainable mobility in order to alleviate resource consumption and environmental impacts in cities. Nevertheless, the integration of life cycle environmental criteria in the design and management of the urban infrastructures required to support sustainable mobility is usually missing. Given the vast span and increasing global investment in the deployment of new infrastructure, the environmental burden imposed to the urban public space can be significant. This dissertation concentrates on the characterization of the life-cycle environmental performance of conventional designs of (concrete, asphalt and granite) sidewalks and charging facilities for electric vehicles (two-wheelers). Sidewalks are basic urban pavements implemented to support walking and cycling as the cleanest modes of urban mobility. Sidewalks also represent the matrix for the layout of different urban elements required to support sustainable mobility. Charging facilities for electric vehicles represent one urban element being heavily implemented in cities to encourage the electricification of the urban vehicle fleet as a promising strategy to cut oil consumption and pollutant emissions from motorized mobility. Life Cycle Assessment is applied in order to identify the most environmentally-friendly solutions and best practices to minimize the environmental burden imposed to the urban public space, thereby increasing the value of greening urban mobility. The dissertation also looks for solutions to improve the environmental performance of those product systems with high environmental footprint in order to achieve major environmental improvements at the urban scale. On the one hand, the potential for cleaner industrial production of granite tiles used in construction is analyzed from an Industrial Ecology approach (technological improvement, rainwater harvesting and by-product synergies). On the other hand, ecodesign principles are applied in the conceptualization of an eco-pergola (street furniture) that can contribute to support multimodal (pedestrian and e-bike) mobility. As a result, this dissertation provides complete and disaggregated inventory data of the mobilized resources (energy, water, materials) and environmental impacts of the life cycle of each product system, identifies the most relevant hot-spots for environmental improvement and defines a set of criteria and best-practices for sustainability-based decision-making to minimize the environmental burden of the urban public space.

Climate change is a global challenge that requires proactive action from municipalities, companies, and other organizations to prioritize sustainability in their daily operations. In the past few decades, life cycle assessment (LCA) approach has been successfully applied for environmental assessments in the drinking water sector. In this study, this approach has been used to present a comparative evaluation of the potential environmental impacts associated with nine different process alternatives for future drinking water production at Norrvatten. This study is a pioneering one that explores the potential of LCA as a decision support tool to prioritize and optimize environmental impacts during the operational phase in Swedish drinking water production. The nine alternatives are designed for the year 2050 to meet the average daily demand of 208 MLD for the 14 municipalities in the northern Stockholm region that Norrvatten supplies with drinking water. Out of the nine alternatives, the alternative based on direct filtration of raw water on nanofiltration membranes came out as the most environmentally friendly solution due to the use of renewable electricity from hydro and wind power. The results indicate that the potential environmental impacts are dominated by the use of chemicals in all alternatives, which in turn depends on the energy sources used for chemical production that are mostly dominated by fossil-based non-renewable sources. The impacts due to transportation and energy consumption are relatively less in Swedish drinking water production. Moreover, filtration through granulated activated carbon (GAC) is the most environmentally damaging treatment step, but regeneration of saturated GAC induces positive impacts in all alternatives. Among environmental impact categories, categories related to fine particulate matter formation; global warming, human carcinogenic toxicity, and human non-carcinogenic toxicity are the most significant in all alternatives. Several of the treatment technologies included in the nine alternatives, such as Nanofiltration, have only been tested on a pilot scale and have not been used for drinking water production at Norrvatten. So this study should be followed up and supplemented with better representative inventory data relevant to the Swedish context in order to contribute more effectively in making the future Swedish drinking water production more sustainable and environmentally friendly. Also, this study is based on the most recently available data that may not be valid in 2050 and the latest trends to substitute non-renewable energy sources with renewable sources may reduce the impacts due to chemical production and transportation in the future. Moreover, this LCA study does not include any aspects of water quality and treatment costs. Hence, while comparing different alternatives, the quality of the treated water and its production cost must also be taken into account.
Klimatförändringar är en global utmaning som kräver proaktivt agerande från kommuner, företag och andra organisationer för att prioritera hållbarhet i sin dagliga verksamhet. Under de senaste decennierna har livscykelanalys (LCA) använts för miljöbedömningar inom VA-sektorn. I denna studie har detta tillvägagångssätt använts för att presentera en jämförande utvärdering av den potentiella miljöpåverkan som är förknippad med den framtida dricksvattenproduktionen vid Norrvatten. Med hjälp av LCA så jämförs nio olika processalternativ för den framtida produktionen och kan på så sätt bidra till att prioritera och optimera processval utifrån miljösynpunkt. De nio alternativen är utformade för år 2050 för att tillgodose den genomsnittliga dagliga efterfrågan på 208 MLD för de 14 kommuner i norra Stockholmsregionen som Norrvatten försörjer med dricksvatten. Av nio alternativ kom alternativet baserat på direkt filtrering av råvatten på nanofiltreringsmembran som den mest miljövänliga lösningen på grund av användningen av förnybar el från vatten- och vindkraft. Resultaten indikerar att de potentiella miljöeffekterna domineras av användning av kemikalier i samtliga alternativ, vilket i i sin tur beror på de energikällor som används för kemikalieproduktion domineras av fossilbaserade energibärare. Effekterna på grund av transport och energiförbrukning är relativt låg i svensk dricksvattenproduktion. Filtrering genom granulerat aktivt kol (GAC) det mest miljöbelastande behandlingssteget, men regenerering av mättad GAC ger positiva effekter i alla alternativ. Bland kategorier för miljöpåverkan så är kategorier relaterade till bildning av fina partiklar; global uppvärmning, mänsklig cancerframkallande toxicitet och mänsklig icke-cancerogen toxicitet de viktigaste i alla alternativ. Flera av de behandlingstekniker som ingår i de nio alternativen, såsom Nanofiltration, har enbarts testats i pilotskala och inte använts för dricksvattenproduktion vid Norrvatten. Så denna studie bör följas upp och kompletteras med data som är relevanta för förhållanden vid Vättern Denna studie baseras också på tillgängliga data som kanske inte är giltiga 2050 och de senaste trenderna för att ersätta icke förnybara energikällor med förnybara källor som kan minska effekterna på grund av kemisk produktion och transport i framtiden. Dessutom innehåller denna LCA-studie inga aspekter av vattenkvalitet och behandlingskostnader.. Vid jämförelse av olika alternativ måste även kvaliteten på det behandlade vattnet och dess produktionskostnad beaktas.

Mestrado em Métodos Quantitativos para a Decisão Económica e Empresarial
A Science4you S.A. é uma empresa portuguesa, com sede em Loures (MARL), que produz brinquedos científicos e educativos e presta outros serviços para crianças. A fábrica conta com 17744 referências, sendo 6641 referentes a produto final. A produção desta empresa está dividida por secções. Na secção de produção primária são enchidos os frascos. Na secção de produção intermédia é feita a etiquetagem e a arrumação dos diferentes componentes em sacos. As caixas são montadas nas duas secções de produção final. O produto final é classificado de acordo com três níveis de prioridade: prioridade elevada, para os produtos de campanha; prioridade intermédia para os produtos de stock; e prioridade baixa, para os produtos de buffer stock. A produção é orientada de acordo com objetivos diários, não existindo, atualmente, um procedimento sistemático de afetação dos recursos humanos disponíveis. Com o objetivo de encontrar uma afetação diária dos trabalhadores às diferentes tarefas envolvidas na produção, propõe-se uma abordagem de programação linear por metas hierarquizadas que minimiza os desvios entre os objetivos de produção e a produção efetiva. O modelo é aplicado a um dia de produção, e os resultados obtidos indiciam que esta abordagem poderá ser útil no cumprimento dos objetivos de produção.
Science4you S.A. is a Portuguese company, based in Loures (MARL), that produces scientific and educational toys and provides other services for children. The factory has 17744 references, 6641 of these are final products. The production is divided into sections. In the primary production section, the vials are filled. In the intermediate production section, the labeling and storage of the different components in bags is carried out. The boxes are assembled in the two final production sections. The final product is classified according to three priority levels: high priority for the campaign products; intermediate priority for stock products; and low priority, for buffer stock products. The production is oriented according to daily objectives, and there is currently no systematic procedure for allocating available human resources. In order to find a daily allocation of workers to the different tasks involved in the production, a goal programming approach is proposed by hierarchical goals that minimizes deviations between production objectives and actual production. The model is applied to a day of production and the results indicate that this approach may be useful in meeting the production objectives.
info:eu-repo/semantics/publishedVersion

During the past several decades, agricultural intensification has been crucial to increase the food supply. Several processes related to intensification are very detrimental to the environment, particularly biodiversity. Today, agriculture is facing the challenge of satisfying its demand for food while improving its environmental sustainability. Knowledge of the shape of the relationship between biodiversity and intensity is necessary to determine both where conservation policies will be most effective and how to allocate intensity to reconcile production and biodiversity. Few empirical studies on this relationship exist, and the influence of the spatial arrangement of intensity on biodiversity remains untested. This Ph.D. thesis determined how to target both agricultural intensity and its spatial allocation for meeting production and conservation objectives of farmlands. To answer this research question, we used a country-scaled approach that combined two France-scaled databases that describe agriculture and farmland birds. We characterized a nationwide gradient of agricultural intensity and studied a farmland bird community along this gradient, using several trait-based descriptors (specialization, trophic level, and species main habitat). Agricultural intensity and bird communities were described at the Small Agricultural Region (SAR; mean width = 22.4 km) level. As a first step, we developed a novel method to estimate an intensity indicator that was based on Input Costs/ha, with SAR resolution. This indicator provides a continuous intensity measure that is relevant across different types of agricultural systems. Secondly, we investigated the effects of a gradient of land uses (grassland to arable land) and its heterogeneity on the bird community. We found habitat specialists suffered from habitat loss, while generalists benefited from heterogeneity. Thirdly, we showed that the community responded significantly to intensity, with winner species replacing loser species along the gradient. The shift between losers and winners was sharper at low intensities. Interestingly, spatial aggregation of intensity had a strengthening effect on the bird community. Finally, the relationships linking intensity to the bird community, food production, and economic performance were integrated into a model aimed at optimizing intensity allocation. Optimal allocations reached win-no-lose solutions with the three criteria. They corresponded to targeted intensity modifications: many small changed, favoring homogeneous, extensive clusters, were optimal within an extensification scenario; while a few large changes, favoring heterogeneity, were optimal within an intensification scenario. We provide one of the first studies demonstrating that spatial aggregation of intensity can influence the biodiversity/intensity relationship. Our results also provide an opportunity to improve the effectiveness of conservation policies, at national scales, with spatial targeting: opposite targeting should be performed either to maximize biodiversity benefits or to increase production, while mitigating biodiversity impacts. Our results highlight the importance of mixed allocation strategies between land sparing/sharing extremes. In order to put these opportunities into effect, further research should address the technical solutions that achieve intensity modification at the farm level and design targeted policies that benefit biodiversity and other environmental criteria

This master’s thesis is focused on opportunities of optimization of electric power consumption from photovoltaic power plant. In theoretical part are presented basic principles and possibilities of photovoltaic system connection. It continues with an overview of backup systems and types of batteries. Practical part is about prediction of production and consumption of electric power, possibilities of power management and optimization. Next chapter deals with battery life cycle and their suitability for photovoltaic system. The last part of this thesis is the quantification of the stored electric energy economic value.

The aim of this diploma thesis is a detailed view of a process and way of managing all the sourcing activities in the company Thermo Fischer Scientific. The focus (of my work) is a czech site of mentioned company situated in Mukařov, which, apart from production itself, is engaged also in sourcing for its own needs (where in most cases it has a decision power in its own hands) as well as for the whole company in the global measure (where it operates just as an intermediate searching for possible business partners, without any powers of decision). The main contribution of my work lies in the comparison of both of these variations and detailed investigation and description of all the activities that could help to optimize the global sourcing. I found out that entire optimizations are based on communication improvements among all the sourcing managers and technologists within the global corporation. On the basis of this fact I have projected models of documents the sourcing managers should work with, suppliers database and an information server. The result of my work is a process scheme which should contribute to the outsourced projects optimization.

L' oncoprotéine E6 - qui joue un rôle crucial dans le processus d'oncogenèse induit par les papillomavirus a longtemps résisté à toute analyse. Depuis 1995 l'équipe Oncoprotéines a concentré ses efforts sur cette problématique. Ce qui a permis la résolution par RMN de la structure du domaine C-terminal de E6 en 2006. C'est dans ce cadre que j'ai commencé ce Doctorat en 2008, avec objectif de continuer la quête de données structurales sur E6 tout en acquérant des informations sur ses modes d'interaction avec ses cibles cellulaires. Les travaux de cette thèse ont permis l'obtention de la structure cristallographique de E6 (HPV16) en complexe avec un peptide de E6AP, en utilisant une approche originale capable de produire des protéines E6 stables et solubles. Cette structure constitue la première information structurale publiée sur des protéines E6 entières, attendue depuis plus de 20 ans par la communauté scientifique. J'ai effectué également durant cette thèse une analyse du système d'interaction de la protéine E6 basée sur une large étude d'interaction entre les protéines E6 (7 types) et 93 peptides porteurs de motif LxxLL.

Les travaux présentés dans cette thèse portent sur la conception de systèmes de fabrication en contexte incertain. La conception d'un tel système peut être vue comme un problème d'optimisation qui consiste à trouver une configuration qui permet d'optimiser certains objectifs tout en respectant des contraintes technologiques et économiques connues. Les systèmes de fabrication étudiés dans ce mémoire sont des lignes d'assemblage et d'usinage. La première est une ligne qui se présente comme une chaîne de postes de travail où, dans chaque poste, les opérations d'assemblage s'exécutent de manière séquentielle. La deuxième, quant à elle, est une ligne particulière qui se compose de machines de transfert comportant plusieurs boîtiers multibroches où les opérations s'exécutent simultanément. Dans un premier temps, nous décrivons de différentes approches permettant de modéliser l'incertitude des données en optimisation. Une attention particulière est portée sur les deux approches suivantes : l'approche robuste et l'analyse de sensibilité. Puis, nous présentons trois applications : la conception d'une ligne d'assemblage et d'une ligne d'usinage soumises aux variations de temps opératoires et la conception d'une ligne d'assemblage avec les temps opératoires connus sous la forme d'intervalles des valeurs possibles. Pour chaque application, nous identifions les performances attendues ainsi que la complexité de la prise en compte de l'incertitude. Ensuite, nous proposons de nouveaux critères d'optimisation en adéquation avec la problématique introduite. Enfin des méthodes de résolution sont développées pour appréhender les différents problèmes mis en évidence par ces critères.

Tesis por compendio
[ES] Algunos productos se caracterizan por su falta de homogeneidad, lo que significa que productos con diferentes características pueden ser obtenidos de un mismo proceso de producción debido a factores incontrolables como la naturaleza de las materias primas o las condiciones ambientales durante la producción. Hay cuatro aspectos que caracterizan la falta de homogeneidad en el producto: los subtipos homogéneos que se obtienen de un mismo lote de producción, la cantidad de productos que componen cada subtipo, el valor de cada uno de los subtipos, y el estado de los productos. La falta de homogeneidad en el producto dificulta la gestión de los procesos de las empresas y cadenas de suministro en el momento en el que los clientes requieren homogeneidad entre las unidades de producto que adquieren. Un ejemplo de esto se produce en el sector de la cerámica, en el que los clientes requieren que todas las unidades que van a ser ensambladas juntas tengan el mismo color, espesor y calidad por razones estéticas y de seguridad. Otro ejemplo es el extraído del sector agroalimentario, en el que el mercado final requiere productos que cumplan con un tamaño mínimo, un color particular, o sabor en el caso de las frutas. Además, el sector agroalimentario tiene la complejidad añadida producida por el deterioro de los productos a lo largo del tiempo, y la necesidad de los mercados de ofrecer a los clientes productos con una mínima duración tras su venta. En esta Tesis, se define como productos heterogéneos a aquellos productos que se pueden clasificar en subtipos homogéneos con una cantidad variable, mientras que los productos perecederos son aquellos que, además de ser heterogéneos, tienen falta de homogeneidad en su estado. De acuerdo con estos conceptos, el sector cerámico comercializa productos heterogéneos mientras que el sector agroalimentario comercializa productos perecederos. Esta Tesis propone marcos conceptuales y modelos de Investigación Operativa que soporten la gestión de cadenas de suministro con productos heterogéneos y perecederos en la toma de decisiones centralizada y distribuidas relacionadas con los niveles de decisión estratégica, táctica y operativa. El objetivo es mejorar la competitividad, sostenibilidad y flexibilidad de la cadena de suministro para adaptarse a los requerimientos del mercado bajo condiciones de incertidumbre. Para esto, se han propuesto modelos de Investigación Operativa deterministas e inciertos, cuyos resultados se comparan concluyendo que los resultados obtenidos con los modelos inciertos se adaptan mejor al comportamiento real de las cadenas de suministros.Los modelos de Investigación Operativa propuestos han contribuido a tres áreas de investigación: problemas operativos en el sector cerámico, problemas estratégicos en el sector agroalimentario y problemas de planificación en el sector agroalimentario. Las principales novedades en los problemas operativos en el sector cerámico son el modelado de las características de las baldosas cerámicas, la consideración de los requerimientos de homogeneidad entre unidades de diferentes líneas de pedido, y la posibilidad de realizar entregas parciales y entregas con retraso. Esta Tesis contribuye a los problemas estratégicos en el sector agroalimentario al diseñar una cadena de suministro completa de productos agroalimentarios frescos considerando el aspecto perecedero de los productos e integrando decisiones tácticas, y determinando el impacto real que tiene considerar el aspecto perecedero de los productos durante el diseño de la cadena de suministro ...
[CA] Alguns productes es caracteritzen per la seua falta d'homogeneïtat, el que significa que productes amb diferents característiques poden ser obtinguts d'un mateix procés de producció degut a factors incontrolables com la naturalesa de les matèries primeres o les condicions ambientals durant la producció. Hi ha quatre aspectes que caracteritzen la falta d'homogeneïtat en el producte: els subtipus homogenis que s'obtenen d'un mateix lot de producció, la quantitat de productes que componen cada subtipus, el valor de cada un dels subtipus, i l'estat dels productes. La falta d'homogeneïtat en el producte dificulta la gestió dels processos de les empreses i cadenes de subministrament en el moment en què els clients requerixen homogeneïtat entre les unitats de producte que adquirixen. Un exemple d'açò es produïx en el sector de la ceràmica, en el que els clients requerixen que totes les unitats que seran acoblades juntes tinguen el mateix color, grossària i qualitat per raons estètiques i de seguretat. Un altre exemple és l'extret del sector agroalimentari, en el que el mercat final requerix productes que complisquen amb una grandària mínima, un color particular, o sabor en el cas de les fruites. A més, el sector agroalimentari té la complexitat afegida produïda pel deteriorament dels productes al llarg del temps, i la necessitat dels mercats d'oferir als clients productes amb una mínima duració després de la seua venda. En aquesta Tesi, es definix com a productes heterogenis a aquells productes que es poden classificar en subtipus homogenis amb una quantitat variable, mentres que els productes peribles són aquells que, a més de ser heterogenis, tenen falta d'homogeneïtat en el seu estat. D'acord amb aquests conceptes, el sector ceràmic comercialitza productes heterogenis mentres que el sector agroalimentari comercialitza productes peribles. Aquesta Tesi proposa marcs conceptuals i models d'Investigació Operativa que suporten la gestió de cadenes de subministrament amb productes heterogenis i peribles en la presa de decisions centralitzada i distribuïdes relacionades amb els nivells de decisió estratègica, tàctica i operativa. L'objectiu és millorar la competitivitat, sostenibilitat i flexibilitat de la cadena de subministrament per adaptar-se als requeriments del mercat sota condicions d'incertesa. Per a açò, s'han proposat models d'Investigació Operativa deterministes i incerts, els resultats es comparen concloent que els resultats obtinguts amb els models incerts s'adapten millor al comportament real de les cadenes de subministraments. Els models d'Investigació Operativa proposats han contribuït a tres àrees d'investigació: problemes operatius en el sector ceràmic, problemes estratègics en el sector agroalimentari i problemes de planificació en el sector agroalimentari. Les principals novetats en els problemes operatius en el sector ceràmic són el modelatge de les característiques de les rajoles ceràmiques, la consideració dels requeriments d'homogeneïtat entre unitats de diferents línies de comanda, i la possibilitat de realitzar lliuraments parcials i lliuraments amb retard. Aquesta Tesi contribueix als problemes estratègics en el sector agroalimentari al dissenyar una cadena de subministrament completa de productes agroalimentaris frescos considerant l'aspecte perible dels productes, integrant decisions tàctiques, i determinant l'impacte real que té considerar l'aspecte perible dels productes durant el disseny de la cadena de subministrament ...
[EN] Some products are characterised by their lack of homogeneity, what means that products with different characteristics can be obtained from the same production process due to uncontrollable factors such as the nature of raw materials or the environmental conditions during production. There are four aspects that characterize the lack of homogeneity in the product: the homogeneous subtypes to be obtained from a production lot, the quantity of products that belong to each subtype, the value related to each of the subtypes and the state of the products. The lack of homogeneity in the product hinders the management of the supply chain or company's processes at the time customers require the homogeneity among the acquired units of product. An example of this is produced in the ceramic tile sector, in which customers need all acquired ceramic tiles that are going to be jointly assembled to have the same colour, thickness and quality for aesthetic and safety reasons. Another example is the extracted from the agri-food sector, in which final markets require products that meet some characteristics such as a minimum size, a particular colour or flavour in the case of fruits. In addition, the agri-food sector has the added complexity produced by the deterioration of products over time, and the need of markets to offer to end consumers products with a minimum durability after sale. In this Thesis, heterogeneous products are defined as products for which different subtypes can be obtained in a variable quantity while perishable products are those that, apart from being heterogeneous, have a lack of homogeneity in their state. According to these concepts, ceramic sectors would commercialize heterogeneous products while the agri-food sector would do so with perishable products. This Thesis proposes conceptual frameworks and Operations Research models to support the management of supply chains with heterogeneous and perishable products in centralized and distributed decision-making processes related to strategic, tactical and operative decisional levels. The objective is to improve the supply chain competitiveness, sustainability and flexibility to adapt to market requirements under uncertain conditions. For this, both deterministic and uncertain Operations Research models have been proposed, whose results are compared concluding that results obtained with uncertain models better fit with the behaviour of real supply chains. The proposed Operations Research models have contributed to three research areas: operational problems in the ceramic sector, strategic problems in the agri-food sector and planning problems in the agri-food sector. Main novelties in the ceramic operational problems are the modelling of the characteristics of ceramic tile products, the consideration of homogeneity requirements between units from different order lines, and the possibility of making partial deliveries and delayed deliveries. This Thesis contributes to strategic problems in agri-food products by designing an entire fresh agri-food supply chain considering the perishability of products and integrating tactical decisions, and by determining the real impact that considering the products' perishability has on the supply chain design process ...
This Thesis has been developed in the Research Centre of Management and Production Engineering (CIGIP, for its acronym in Spanish “Centro de Investigación en Gestión e Ingeniería de Producción”) of the Universitat Politècnica de València with the support of the predoctoral grant Programme of Formation of University Professors (FPU, for its acronym in Spanish “Formación de Profesorado Universitario”) from the Spanish Ministry of Science, Innovation and Universities (Ref. FPU15/03595). The supervisors of this Thesis are Dr. Angel Ortiz, and Dra. María del Mar Alemany Diaz that are Professors in the Research Centre of Management and Production Engineering (CIGIP) of the Universitat Politècnica de València. The FPU grant has been endorsed by the supervisor Dr. Ángel Ortiz. This Thesis has also been supported by the project ‘RUC-APS: Enhancing and implementing Knowledge based ICT solutions within high Risk and Uncertain Conditions for Agriculture Production Systems’ (Ref. 691249) funded by the EU under its funding scheme H2020-MSCA-RISE-2015, the project ‘Methods and models for operations planning and order management in supply chains characterised by uncertainty in production due to the lack of product uniformity’ (PLANGES-FHP) (Ref. DPI2011- 23597) funded by the Spanish Ministry of Economy and Competitiveness. The projects RUC-APS and PLANGES-FHP have been led by the one of the supervisors of this Thesis Dr. María del Mar Eva Alemany. In order to obtain the international mention for this Thesis, three months of research stages have been made in the research agency Agenzia Lucana di Sviluppo e di Innovazione in Agricoltora, located in Metaponto (Italy)
Esteso Álvarez, A. (2020). Operations research models for the management of supply chains of perishable and heterogeneous products in uncertain contexts. Application to the agri-food and ceramic sectors [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/141099
TESIS
Compendio

L’objectif de ce travail est de développer un cadre méthodologique et générique d’éco-conception de procédés chimiques couplant des outils de modélisation et de simulation traditionnels de procédés (HYSYS, COCO, ProSimPlus et Ariane), d’Analyse du Cycle de Vie (ACV), d’optimisation multiobjectif basée sur des Algorithmes Génétiques et enfin des outils d’aide à la décision multicritère (ELECTRE, PROMETHEE, M-TOPSIS). Il s’agit de généraliser, d’automatiser et d’optimiser l’évaluation des impacts environnementaux au stade préliminaire de la conception d’un procédé chimique. L’approche comprend trois étapes principales. Les deux premières correspondent d’une part aux phases d’analyse de l’inventaire par calcul des bilans de matière et d’énergie et d’autre part à l’évaluation environnementale par ACV. Le problème du manque d’information ou de l’imprécision dans les bases de données classiques en ACV pour la production d’énergie notamment sous forme de vapeur largement utilisée dans les procédés a reçu une attention particulière. Une solution proposée consiste à utiliser un simulateur de procédés de production d’utilités (Ariane, ProSim SA) pour contribuer à alimenter la base de données environnementale en tenant compte de variations sur les conditions opératoires ou sur les technologies utilisées. Des sous-modules « énergie » sont ainsi proposés pour calculer les émissions relatives aux impacts liés à l’utilisation de l’énergie dans les procédés. La troisième étape réalise l’interaction entre les deux premières phases et l’optimisation multi-objectif qui met en jeu des critères économiques et environnementaux. Elle conduit à des solutions de compromis le long du front de Pareto à partir desquelles les meilleures sont choisies à l’aide de méthodes d’aide à la décision. L’approche est appliquée à des procédés de production continus : production de benzène par hydrodéalkylation du toluène HDA et production de biodiesel à partir d’huiles végétales. Une stratégie à plusieurs niveaux est mise en oeuvre pour l'analyse de l'optimisation multi-objectif. Elle est utilisée dans les deux cas d'étude afin d'analyser les comportements antagonistes des critères
The objective of this work is to propose an integrated and generic framework for eco-design coupling traditional modelling and flowsheeting simulation tools (HYSYS, COCO, ProSimPlus and Ariane), Life Cycle Assessment, multi-objective optimization based on Genetic Algorithms and multiple criteria decision-making methods MCDM (Multiple Choice Decision Making, such as ELECTRE, PROMETHEE, M-TOPSIS) that generalizes, automates and optimizes the evaluation of the environmental criteria at earlier design stage. The approach consists of three main stages. The first two steps correspond respectively to process inventory analysis based on mass and energy balances and impact assessment phases of LCA methodology. Specific attention is paid to the main issues that can be encountered with database and impact assessment i.e. incomplete or missing information, or approximate information that does not match exactly the real situation that may introduce a bias in the environmental impact estimation. A process simulation tool dedicated to production utilities, Ariane, ProSim SA is used to fill environmental database gap, by the design of specific energy sub modules, so that the life cycle energy related emissions for any given process can be computed. The third stage of the methodology is based on the interaction of the previous steps with process simulation for environmental impact assessment and cost estimation through a computational framework. The use of multi-objective optimization methods generally leads to a set of efficient solutions, the so-called Pareto front. The next step consists in identifying the best ones through MCDM methods. The approach is applied to two processes operating in continuous mode. The capabilities of the methodology are highlighted through these case studies (benzene production by HDA process and biodiesel production from vegetable oils). A multi-level assessment for multi-objective optimization is implemented for both cases, the explored pathways depending on the analysis and antagonist behaviour of the criteria

Les Energies Marines Renouvelables (EMR) se développent aujourd’hui très vite tant au niveau de la recherche amont que de la R&D, et même des premiers démonstrateurs à la mer. Parmi ces EMR, l'énergie des vagues présente un potentiel particulièrement intéressant. Avec une ressource annuelle brute moyenne estimée à 40 kW/m au large de la côte atlantique, le littoral français est plutôt bien exposé. Mais l’exploitation à grande échelle de cette énergie renouvelable ne sera réalisable et pertinente qu'à condition d'une bonne intégration au réseau électrique (qualité) ainsi que d'une gestion et d'un dimensionnement optimisé au sens du coût sur cycle de vie. Une première solution de génération tout électrique pour un houlogénérateur a d’abord été évaluée dans le cadre de la thèse de Marie RUELLAN menée sur le site de Bretagne du laboratoire SATIE (ENS de Cachan). Ces travaux ont mis en évidence le potentiel de viabilité économique de cette chaîne de conversion et ont permis de poser la question du dimensionnement de l’ensemble convertisseur-machine et de soulever les problèmes associés à la qualité de l’énergie produite. Puis une seconde thèse a été menée par Judicaël AUBRY dans la même équipe de recherche. Elle a consisté, entre autres, en l’étude d’une première solution de traitement des fluctuations de la puissance basée sur un système de stockage par supercondensateurs. Une méthodologie de dimensionnement de l’ensemble convertisseur-machine et de gestion de l’énergie stockée fut également élaborée, mais en découplant le dimensionnement et la gestion de la production d’énergie et de ceux de son système de stockage. Le doctorant devra donc : 1. S’approprier les travaux antérieurs réalisés dans le domaine de la récupération de l’énergie des vagues ainsi que les modèles hydrodynamiques et mécaniques réalisés par notre partenaire : le LHEEA de l’Ecole Centrale de Nantes - 2. Résoudre le problème du couplage entre dimensionnement/gestion de la chaîne de conversion et dimensionnement/gestion du système de stockage. 3. Participer à la réalisation d’un banc test à échelle réduite de la chaine électrique et valider expérimentalement les modèles énergétiques du stockage et des convertisseurs statiques associés - 4. Proposer une méthodologie de dimensionnement de la chaine électrique intégrant le stockage et les lois de contrôle préalablement élaborées 5. Déterminer les gains en termes de capacités de stockage obtenus grâce à la mutualisation de la production (parc de machines) et évaluer l’intérêt d’un stockage centralisé - 6. Analyser l’impact sur le réseau d’une production houlogénérée selon divers scenarii, modèles et outils développés par tous les partenaires dans le cadre du projet QUALIPHE. L’exemple traité sera celui de l’Ile d’Yeu (en collaboration avec le SyDEV
The work of this PhD thesis deals with the minimization of the per-kWh cost of direct-drive wave energy converter, crucial to the economic feasibility of this technology. Despite the simplicity of such a chain (that should provide a better reliability compared to indirect chain), the conversion principle uses an oscillating system (a heaving buoy for example) that induces significant power fluctuations on the production. Without precautions, such fluctuations can lead to: a low global efficiency, an accelerated aging of the fragile electrical components and a failure to respect power quality constraints. To solve these issues, we firstly study the optimization of the direct drive wave energy converter control in order to increase the global energy efficiency (from wave to grid), considering conversion losses and the limit s from the sizing of an electrical chain (maximum force and power). The results point out the effect of the prediction horizon or the mechanical energy into the objective function. Production profiles allow the study of the flicker constraint (due to grid voltage fluctuations) linked notably to the grid characteristics at the connection point. Other models have also been developed to quantify the aging of the most fragile and highly stressed components, namely the energy storage system used for power smoothing (with super capacitors or electrochemical batteries Li-ion) and power semiconductors.Finally, these aging models are used to optimize key design parameters using life-cycle analysis. Moreover, the sizing of the storage system is co-optimized with the smoothing management

碩士
國立清華大學
工業工程與工程管理學系
104
The aim of proposed research is to build a representative simulation model and implement experimental design and response surface methodology (RSM) to analyze the effect between system parameters and key performance indicators. Subsequently, the optimal setting of footwear production line can be determined. A simulation optimization framework is proposed and validated by an empirical study. In the optimization process, transfer batch size, material arrival frequency, number of shoe lasts and the turnover of shoe last are the selected parameters. After screening factors, they are determined that they can affect throughput, cycle time and machine utilization significantly. The first-order model is built by experimental design in order to analyze the curvature effect of model. Furthermore, the second-order model is constructed by RSM and central composite design. An optimal setting and predicted response are evaluated through the contour, surface plots and analysis of response surface. Moreover, the stationary and canonical analysis are performed to identify whether predicted response is maximum, minimum or saddle point. The empirical study is divided into two parts, single-objective and multi-objective optimization. The multi-objective is optimized by using desirability function and optimization software. The experiment result shows that both of their predicted responses are better than current setting.

碩士
國立勤益科技大學
研發科技與資訊管理研究所
100
With the development of science and technology, the manufacture process integrates with skills of automation and intelligence. People gradually find that manual labor can be replaced by machine labor. And because of the increasing demand of large kind of goods and small orders, traditional method of specific path processing applied with mechanical arm in the production line can not fulfill nowadays manufacturing. In that case, highly flexible and multi-functional multi-joint robotic arms will become the mainstream product of the market stage by stage. While mainland China grows more and more prosperous, teenagers who were born after 1990 are no longer willing to devote themselves to the low-tech and low-wage jobs of manufacturing. Therefore, the trend of future manufacturing is automation. However, the more automatic the production line is, the more money is to be invested. Sufficient corresponding measures should be taken when designing the process of the production line. The purpose of the research is to draw an effective, modularized, automatic and labor-economizing design of production line, to help factory managers decide optimized production scheduling and the learning curve, and reach the balance between standardization and flexiblizaiton. The research steps are as follow: first, construct the AHP questionnaire, survey in the small and medium enterprises and summarize factors that are considered in production line designing. Second, through the TRIZ system, we analyze dimensions that affect the production process,use brainstorming and contradiction matrix to get the solution, and then implement the TRIZ rules into the improvement of the case company’s production process. Finally, verify the optimized configuration of the improved production line by using FLEXSIM systems. Integrated with AHP and TRIZ , the research come to conclusions of improving the production line, which are (1) transfer the traditional production-line into an automation one and change the manual labor into the mechanic arm. (2) by using simulation software, study the production status in advance and take measures of improvement and prevention beforehand. (3) improve the detect system, enlarge the temporary storage section, decrease the amount of defective products and increase the process quality. After adopting the suggestions above, the output of the production-line increase by 50% and the labor of 40 persons is replaced by the combination of 11 mechanic arms and 7 persons. Not only the production is increased, but also the human resource cost is cut down. The conclusion of the research helps factories become more effective and more economic.

碩士
國立中正大學
企業管理研究所
101
Nowadays, custom-made product has become a trend in all areas of industries. However, most buyers will not accept longer or even tardy delivery date although products have become more diversified. The date of delivery is shorter, the cash flows will be more flexible, and the risk will also be much lower. Recently, most enterprises tend to keep a conservative way when they deal with a business due to economic contraction and recession around the world. Besides, the price is another major point affecting the business. Hence, in addition to the increment in equipment and manpower, the crucial factor for manufacturers to gain successful transactions and meet the promised delivery date depends on the good quality of dispatch in manpower and machines. With regard to the staff arrangement in traditional manufacturing, it is often based on the empirical rules. There were no significant problems in small-size industries and they could reach the goal on schedule most of the time. However, it is difficult to get the perfect benefit because it is hard to arrange numerous manpower and various products properly. For study purpose, we investigate a manufacturer for Auto-parts and accessories. The objectives of this research are two-fold: (1) to arrange the limited manpower to finish the work as the lowest cost, (2) to finish the work as quick as possible in order to respond to order shuffling or rush order during peak season. In this study, we developed two mixed integer programming models for achieving the goals. The software of Linear Interactive General Optimizer (LINGO) was applied to run the real-world data and the best statistics were resulted. The methodology proposed in the thesis can shed a light for production manager in efficient allocating the manpower to machines so as to lower the production costs or completion time.

碩士
元智大學
工業工程與管理學系
100
With the fast change of technologies, the competition among industries is fierce. It is an important issue for a sustainable business to keep competitive edge, to reduce the production costs and to quick respond the customer’s demand. Lean six-sigma was introduced in the study to address above issue. Lean six-sigma retain the process and quality improvement project steps from six-sigma, and add the steps for waste elimination and value engineering for process flow from lean production. The study first discussed the six-sigma, lean production and their variants; followed by elaborating the lean six-sigma. A case company, which had a successful six-sigma project history, was studied. The company introduced lean six-sigma as an experiment for its transformer production line. A project team was formed to carry out the project. Besides traditional six-sigma steps, manufacturing processes were carefully studied by the team to eliminate the wastes and to propose new, improved processes. Since the physical layout was not changed, the study used simulation to simulate original process and various new ones. Based on simulation analysis, the bottlenecks in the manufacturing process were identified. Optimal adjustment of resources was done through simulation to achieve higher quantity production and shorter waiting time. Finally, the study gave the summary and future recommendations.

碩士
中原大學
工業工程研究所
102
This technical report explores the use of color filters (abbreviated as CF) process line operating mode to mixed line production On Cell touch sensor problem, an optimization method for parameter setting of machine equipment, and in the case G Company for case study. On Cell touch sensor the control program to import products made with CF mixed line production, its past experience in CF line processes can’t be applied to optimize the model requires the development of a new line of production and mixing parameters. G Company previously made trial and error method parameter optimization, can’t effectively achieve shorter production lead times and product defect rate control purposes, it is neces-sary to propose a set of scientific methods and can improve the yield. To solve this problem, research methods into three steps: (a) the reaction of customer complaint statistics touch products and selected factors adverse conditions are expected to improve (more commonly used only for a certain product specifications), (b) identify the cause Touch optimize product adverse conditions reasons related process and focus on machine equipment (only for a more common product specifications) and experimental de-sign (c) the use of focused machine equipment of important process parameters parameter value (only for certain over the Common product specifications). Where the second step is more complex, but also contains the method used: (i) fish-bone diagram: The purpose is to list the factors of production lines (human, machine, material, method) that might affect; (ii) the quality of cross-functional flowchart: The pur-pose of viewing the production process has to be repeated or whether the process can cause poor production procedures; (iii) Quality function deployment: the purpose is expected to improve the poor conditions, descending one by one narrow and converge to the production line may be adverse conditions machine equipment, parameters, and other factors; (iv) the causal matrix: The aim is by Plato proportional relationship after convergence, a list of key factors affecting processes; (v) Failure Mode Analysis (FMEA): The purpose of affecting the process of the key factors to do RPN values obtained detailed analysis of convergence observed a relatively high fraction of the project, we can focus on machine equipment, parameters. According to the above mentioned methods, found that the parameters of etching ma-chine is focused on improving the parameters, including etching machine of the spray pressure, the conveyor speed and the etchant temperature, found spray pressure which fac-tors are significant factors, while conveying speed and the temperature of the two factors was not significant, moreover considering etchant can be stored for longer without in-creasing the cost of heating elements, in addition to shortening the cycle time of the con-veyance under the consideration of the highest speed setting machine, increase the utiliza-tion rate of production can be improved, finally This combination of parameter values proposed three factors. For combinations of parameter values presented in this technical report, G companies small production test models produced from G's On Cell GP5A3054 product testing results to improve effectiveness analysis consists of two parts (1) Product defect rate analysis and (2) and R control chart analysis. analysis the Product defect ratio, that not improved yield before was 27.27% , sample size was 55 confidence interval (0.1550, 0.3903), the Product defect ratio improved to 2% for the 48 samples, 95% confidence interval for the Product defect ratio = (0.0196, 0.0596) lower average the Product defect ratio 25.27%. From the analysis and R control charts can be seen, there are more points before the improvement beyond the control limits, but many said the process beyond the center position offset spec-ifications far, the improved and R control charts in almost all control limits indicates the process is stable and close to the center of the process specification values. Then again re-duce manufacturing costs partly because lowering rates reduce the cost of making defective products and the amount of cost reduction will change as the utilization rate is different from, utilization rate of 100%, 80%, 60%, respectively, the relative availability Daily cost savings were 11,200,000 NT, 8,960,000 NT, 6,720,000 NT

The objective of reservoir management is to maximize a key performance indicator (net present value in this study) at a minimum cost. A typical approach includes engineering analysis, followed by the economic value of the technical study. In general, operators are inclined to spend more effort on the engineering side to the detriment of the economic area, leading to unbalanced and occasionally suboptimal results. Moreover, most of the optimization methods used for production scheduling focus on a given recovery phase, or medium-term strategy, as opposed to an integrated solution that allocates resources from discovery to field abandonment. This thesis addresses the optimization of a reservoir under both technical and economic constraints. In particular, the method presented introduces a life cycle maximization approach to establish the best exploitation strategy throughout the life of the project. Deterministic studies are combined with stochastic modeling and risk analysis to assess decision making under uncertainty. To demonstrate the validity of the model, this document offers two case studies and the optimal times associated with each recovery phase. In contrast with traditional depletion strategies, where the optimization is done myopically by maximizing the net present value at each recovery phase, our results suggest that time is dramatically reduced when the net present value is optimized globally by maximizing the NPV for the life of the project. Furthermore, the sensitivity analysis proves that the original oil in place and non-engineering parameters such as the price of oil are the most influential variables. The case studies clearly show the greater economic efficiency of this life cycle approach, confirming the potential of this optimization technique for practical reservoir management.
text

Dissertação de Mestrado em Bioquímica apresentada à Faculdade de Ciências e Tecnologia
Solanum betaceum Cav., normalmente designado por tamarilho, pertence à famíliadas solanaceas e é uma planta nativa do sul da América. O tamarilho por sermicropropagado através da técnica embriogénese somática (SE). Duas linhas celularesnão-embriogénicas, provenientes da SE, irão ser estudadas neste trabalho: linha celularnão-embriogénica 1 (NEL 1) e linha celular não-embriogénica 2 (NEL 2).As células induzidas por embriogénese somática podem ser aplicadas a sistemasbiotecnológicos, culturas de células vegetais em suspensão, com o objetivo de estudar eanalisar processos moleculares e celulares numa variedade de espécies de plantas. Estessistemas estão a ser utilizados para produzir proteínas recombinantes e metabolitossecundários. Estes produtos podem ser produzidos em larga escala em bioreatores.Algumas metodologias biotecnológicas têm sido efetuadas para aumentar aprodução dos produtos oriundos das plantas e o uso de elicitadores é uma delas. O uso deelicitadores nas culturas de células vegetais em suspensão podem causar diversos efeitosbiológicos como o aumento da produção de metabolitos secundários. Neste trabalho, doiselicitadores vão ser avaliados: extrato de levedura e hidrolisado de caseína.O objetivo deste trabalho é caracterizar e otimizar linhas celulares de tamarilho emcultura, usando um sistema de bioreator, em termos de:a) Crescimento celular: curvas de crescimento e contagem do número de células;b) Produção de metabolitos: quantificação de proteína, quantificações da massa,perfis de proteína e perfis proteolíticos;c) Influência de elicitadores: quantificação de proteína, quantificações da massa,perfis de proteína e perfis proteolíticos;Os resultados mostraram que a concentração de sucrose presente no meio líquidoafetou a produção de diferentes proteínas, nas duas linhas celulares. A adição de extratode levedura influenciou a produção de hidrolases glicosídicas e fosfatases alcalinas. Ohidrolisado de caseína influenciou o aumento de protéases, mais para a NEL 2 do que paraa NEL 1.
Solanum betaceum Cav., commonly called tamarillo, belongs to the solanaceous family and is a southern America native plant. Tamarillo can be micropropagated throughsomatic embryogenesis (SE) technique. Two non-embryogenic cellular lines ascended fromSE are going to be studied in this work: non-embryogenic cellular line 1 (NEL 1) and nonembryogeniccellular line 2 (NEL 2).Cells induced by somatic embryogenesis can be applied to biotechnologicalsystems, named plant cell suspension cultures, in order to study and analyze cellular andmolecular processes in a variety of plant species. These systems are currently used toproduce important products like recombinant proteins and secondary metabolites.Furthermore, these products can be produce in a large-scale way in liquid sterileenvironments named bioreactors.Some biotechnological approaches have been made for the enhancing of productsproduction by plants and, the use of elicitors is one of them. The use of elicitors in plant cellsuspension cultures may cause several biological effects like an increase in the productionof secondary metabolites. In this work two elicitors are going to be evaluated: yeast extractand casein hydrolyzed.The objective of this work is to characterize and optimize tamarillo cellular linescultures using a bioreactor system in terms of:a) Cellular Growth: growth curves and cell number counting;b) Metabolites production: protein quantification, mass quantifications, proteinprofiles and proteolytic profiles;c) Elicitors influence: protein quantification, mass quantifications, protein profilesand proteolytic profiles.The results showed that the sucrose concentration in liquid medium affected theproduction of different proteins in both cellular lines. Moreover, the addition of yeast extractelicitor influenced the production of glycosidase hydrolases and alkaline phosphates, in bothcellular lines. Casein hydrolyzed influenced the proteases enhance, more in NEL 2 than inNEL 1.
Outro - PTDC/BAA-AGR/32265/2017 : Tamarillo breeding: better plants for better products

碩士
國立高雄第一科技大學
運籌管理研究所
102
In modern production and distribution systems, the automated storage/retrieval systems (AS/RS), high-storage level systems that reduce labor cost, required floor space and error rate, while increasing product availability. The AS/RS system not only has a profound impact on efficiency of material handling, but also on operational efficiency of product line. Generally, AS/RS were equipped at great expense; however, with the aim of reaching higher productivity growth, the application of AS/RS should be given first priority, which is to say that, to design AS/RS system evaluation is inevitable. We consider AS/RS in the support of an assembly line having multiple cells. For the coordination between the assembly line and the AS/RS, two-stage integer programming models are considered and using LINGO mathematical optimization software to construct the IP model. Our goal is to find optimal orders combinations.