Bakgrund: Lagerverksamheten har en väsentlig betydelse och kan vara avgörande för organisationen övergripande prestanda och framgång, i synnerhet för SMF (små och medelstora företag). Driften av lagerverksamheten kan bli särskilt utmanande om organisationen befinner sig i en stark tillväxtfas och om den aktuella artikeln kännetecknas av behov. För att effektivt kunna bedriva sin lagerverksamhet bör organisationer utgå från en lagerdesign. Däremot redogör inte dagens forskning hur SMF som befinner sig i en stark tillväxtfas samt lagerhåller en artikel med behov bör utforma en sådan lagerdesign. Syfte: Denna studie syftar till att föreslå en lagerdesign som tar hänsyn till artikelns behov. Vidare ämnar studien att undersöka vilka konsekvenser en hög tillväxtfas har på ett SMF:s lagerverksamhet. Metod: Studien har studerat organisationen Nordic Green Design AB, ett svenskt SMF vars artikelsortiment utgörs av prydnadsväxter. Artikelns behov förutsätter krav på rätt temperatur, ljus och bevattning. Datainsamlingen har utgått från intervjuer med organisationens lagerpersonal och marknadschef samt via observationer av organisationens befintliga lagerdesign. Data har därefter analyserats utifrån den teoretiska referensramen. Slutsats: Studien betonar vikten av att fastställa behov och krav i samband med utformandet av en lagerdesign, i synnerhet när artikeln präglas av behov. Fastställandet av behov och krav fastställer ramarna för vilka lagerhanteringsmetoder som är tillämpbara i lagerdesignen. Genom att skifta fokus mot fastställandet av behov och krav kan en effektivare lagerverksamhet uppnås. Vidare indikerar studien på att en stark tillväxtfas bidrar till omfattande organisatoriska utmaningar. Studiens resultat antyder att en decentraliserad organisationsstruktur har bäst förutsättningar för att hantera dessa utmaningar. / Background: Warehousing activities are essential and can be crucial to the organizations overall performance and success, especially for SMEs (small and mediumsized enterprises). The warehouse operations can be particularly challenging if the organization is in a rapid growth phase and if the stored article is characterized by requirements. In order to effectively carry out the warehouse operations, organizations need to develop a warehouse design. However, today’s research does not acknowledge how SME’s with above-mentioned prerequisites should form such warehouse design. Purpose: This study aims at proposing a warehouse design that takes into account the requirements of the article. Furthermore, the study intends to examine the consequences of a rapid growth phase on an SME's warehouse. Method: This paper has studied the organization Nordic Green Design AB, a Swedish SME, whose articles consists of ornamental plants. These products require specific care such as temperature, light and irrigation regulation. The data collection was based on interviews with the organization's warehouse staff and marketing manager. Additionally, data was collected through observations of the organization's existing warehouse design. The data has then been analyzed based on the theoretical reference frame. Conclusion: The study emphasizes the importance of identifying needs and requirements when developing a warehouse design, especially when the article is characterized by requirements. The determination of needs and requirements determines the foundation of which storage management methods that are applicable in the warehouse design. By shifting focus to the determination of needs and requirements, more efficient storage can be achieved. Furthermore, the study indicates that a rapid growth phase contributes to extensive organizational challenges. The results of the study suggest that a decentralized organizational structure has the best prerequisites for managing these challenges.

Made available in DSpace on 2016-08-17T18:39:30Z (GMT). No. of bitstreams: 1 2145.pdf: 2206472 bytes, checksum: 5295597725f34bdf5560d6cda8af7446 (MD5) Previous issue date: 2008-03-27 / Financiadora de Estudos e Projetos / Streptococcus pneumoniae (pneumococo) is a pathogenic bacterium that causes several infections which are aggravated by the increase of serotypes with antibiotics resistance. The development of an effective vaccine against this pathogen is crucial for the prevention of the neumococcal illnesses. Conjugated vaccines, consisting of the capsular polysaccharide joined to a carrier protein, are more efficient in the stimulation of the immunologic memory. The capsular polysaccharide (PS) is present in the capsule that involves the cell. Thus, the conjugated vaccine elaboration involves bacterial cells cultivation for its production. As the organism is cultivated in the oxygen absence, the lactate production is inevitably high, leading to growth inhibition due to lactate accumulation in the medium. To minimize the inhibitory effects of the lactate accumulation and to increase the PS production it is necessary to monitor the process and adequately control the addition of supplementary medium along with the withdrawal of saturated medium. This kind of operation can be performed by carrying out a fed-bath cultivation in a bioreactor connected to a perfusion system. The success on the monitoring, control and optimization of this bioprocess depends on the efficiency of the modeling and simulation resources employed. This research work considers the uses intelligent computational techniques, specifically the technique of heuristical search called simulated annealing (SA) combined with neural networks for the state inference and the optimization of S. pneumoniae cultivations. The proposal was implemented as a computational system that: a) uses the SA for the identification of the values for a set of parameters associated to unstructured models and; b) uses neural networks (individually and grouped as a committee) for the state inference of a culture. The work presents and discusses the results of the system for data sets experimentally obtained and highlights the importance of the proposal for achieving a higher efficiency in the culture control processes. / Streptococcus pneumoniae (pneumococo) é uma bactéria patogênica causadora de várias infecções que são agravadas pelo aumento de cepas com resistência aos antibióticos. O desenvolvimento de uma vacina efetiva contra este patógeno é crucial para a prevenção das doenças pneumocócicas. Vacinas conjugadas, constituídas pelo polissacarídeo capsular ligado a uma proteína carregadora, são mais eficientes no estímulo da memória imunológica. O polissacarídeo capsular (PS) está presente na cápsula que envolve a célula e, desta forma, a elaboração de vacinas conjugadas envolve o cultivo da bactéria para a produção do mesmo. Como o microrganismo é cultivado na ausência de oxigênio, a produção de lactato é inevitavelmente elevada e o seu acúmulo no meio provoca a inibição do crescimento. Para minimizar os efeitos inibitórios da acumulação de lactato e aumentar a produção de PS é necessário monitorar o processo e controlar adequadamente a adição de meio suplementar e a retirada de meio saturado em cultivos operados em batelada alimentada, utilizando biorreatores acoplados a sistema de perfusão. O sucesso no monitoramento, no controle e na otimização deste bioprocesso depende da utilização de recursos de modelagem e de simulação que sejam eficientes. Este trabalho de pesquisa propõe o uso de técnicas computacionais inteligentes, especificamente a técnica de busca heurística chamada de simulated annealing (SA) aliada a redes neurais, para a inferência de estado e a otimização de cultivos de S. pneumoniae. A proposta foi concretizada via desenvolvimento de um sistema computacional que: a) faz uso do SA para a identificação do conjunto de valores de parâmetros associados a modelos não estruturados e; b) usa redes neurais (individualmente e em regime de comitê) para a inferência de estado de um cultivo. O trabalho apresenta e discute os resultados do sistema em conjuntos de dados obtidos experimentalmente e evidencia a importância da proposta para uma maior eficiência no controle de processos de cultivo.

Made available in DSpace on 2016-06-02T19:55:31Z (GMT). No. of bitstreams: 1 4085.pdf: 6460777 bytes, checksum: 9367318799fc091b43ee6716e5057271 (MD5) Previous issue date: 2011-12-22 / Financiadora de Estudos e Projetos / High cell density cultivations of recombinant E. coli are a fast and economical way to produce recombinant proteins. Through this bioprocess, products with high added value and pharmaceuticals of great importance such as insulin, human and bovine growth hormone, protein antigens for formulation of vaccines, enzymes, among others, are obtained. However, keeping these cultivations within the desired conditions becomes a major challenge, since some variables such as dissolved oxygen concentration (DOC) and substrate concentration are difficult to control. Therefore, the development and implementation of an automatic monitoring and control tool are key requirements for the performance of high density cultivation. The present work has as main objectives to study feeding strategies for high cell density cultivation of recombinant Escherichia coli and develop a computational tool capable of ensuring the implementation of the chosen strategies, performing the monitoring, control and supervision of the cultivations. Fed batch cultivations were carried out under the supervision of the tool in a 5 L in-house bioreactor, equipped with sensors for temperature, dissolved oxygen, pH, pressure and biomass (sensor that measures the concentration of viable cells based on permittivity measurements), peristaltic pumps and connected to the gas analyzer. The tool was developed with LabView 8.0 and MatLab 6.5, being the acquisition and communication with the different bioreactor accessories via compact Field Point. Twenty two fed-batch cultivations with 5 different clones of E. coli, BL21(D3) expressing the enzyme penicillin G acylase (PGA) as well as antigenic proteins of S. pneumoniae (PspA3, PspA245 and PspA4Pro) and E. rhusiopathiae (SpaA) were performed during the development of the tool and the studies of feeding strategy. Both defined medium (HDF modified) as complex medium (ZYM-5052 modified), usually having glycerol as main carbon source and IPTG or lactose as inducers were used. In all cultivations, samples were collected to quantify the concentration of cells (dry weight method in filter of 0.22 m and optical density at 600 nm), organic acids, glucose, glycerol and lactose (HPLC) as well as protein expression (densitometry and NIPAB method for PGA) and plasmid stability (plating). The tool SUPERSYS_HCDCR (registered as a free software) developed, implemented and validated in the performed cultivations, carries out the basic functions of bioreactor supervision software, such as monitoring and data acquisition of pressure, temperature, pH, DOC, fraction of CO2 and O2 in the outlet gas as well as real-time estimate of the respiratory quotient, the rate of oxygen consumption and CO2 production. However, it also has the following special features, including: i) automatic control of air and oxygen flow according to cellular demand, ii) automatic activation of the feed pump at the end of the batch; iii) automatic control of feeding flow rate as function of the specific growth rate inferred in real time; iv) automatic control of feeding flow rate constrained by the concentration of dissolved oxygen, v) audible alarms indicating failures in the process; vi) failure messages sent via email; vii) automatic control of dissolved oxygen concentration; viii) control of the bioreactor pressure; and ix) control of bath temperature. Regarding the studies of feeding strategies aimed at biomass productivity increase in high cell density cultivations of recombinant E. coli, using the supervision tool developed together with changes in the composition of the synthetic culture medium available in the literature, a cellular concentrations greater than 150 g/L was achieved in less than 24 hours of cultivation, corresponding to a productivity of 9.2 g/Lh. This value, which is higher than the reported in the literature, was obtained without acetate accumulation and allowing high production of recombinant protein. / Cultivos de alta densidade celular de E. coli recombinante constituem uma tecnica rapida e economica para producao de proteinas recombinantes. Por meio deste bioprocesso, sao obtidos produtos de alto valor agregado e de grande importancia na industria farmaceutica, tais como insulina, hormonios de crescimento humano e bovino, antigenos proteicos para formulacao de vacinas, enzimas, dentre outros. Entretanto, manter estes cultivos dentro das condicoes desejadas se torna um grande desafio, em funcao da dificuldade de controlar variaveis como a concentracao de oxigenio dissolvido (COD) e a concentracao de substrato nos niveis desejados. Por isso, o desenvolvimento e a implementacao de sistemas automaticos de supervisao e controle sao requisitos fundamentais para o bom desempenho de um cultivo de alta densidade. O presente trabalho teve como principais objetivos estudar estrategias de alimentacao para cultivos de alta densidade celular de Escherichia coli recombinante e desenvolver uma ferramenta computacional para suporte na execucao das estrategias escolhidas, realizando o monitoramento, controle e supervisao dos cultivos. Os cultivos em batelada alimentada realizados sob supervisao da ferramenta foram conduzidos em biorreator de 5 L, equipado com sensores de temperatura, oxigenio dissolvido, pH, pressao e biomassa (sensor que mede a concentracao de celulas viaveis a partir dos dados de permissividade), bombas peristalticas e conectado a analisador de gases. A ferramenta foi desenvolvida com os programas LabView 8.0 e MatLab 6.5, sendo a aquisicao e a comunicacao com os diferentes acessorios do biorreator realizada via compact Field Point (National Instruments). Vinte e dois cultivos em batelada alimentada com 5 diferentes clones de E. coli, BL21(D3) expressando a enzima penicilina G acilase (PGA) assim como proteinas antigenicas de Streptococcus pneumoniae (PspA3, PspA245 e PspA4Pro) e de Erysipelothrix rhusiopathiae (SpaA) foram realizados durante o desenvolvimento da ferramenta e dos estudos de estrategia de alimentacao, empregando tanto meio definido (HDF modificado) como meio complexo (ZYM-5052 modificado), tendo glicerol ou glicose como principal fonte de carbono e IPTG ou lactose como indutores. Em todos os cultivos, amostras foram coletadas para quantificar a concentracao de celulas (metodo de massa seca em filtro de 0,22m e leitura da densidade otica a 600 nm), de acidos organicos, glicose, glicerol e lactose (HPLC) e a expressao da proteina (densitometria e metodo NIPAB para a PGA) e a estabilidade de plasmideo (plaqueamento). A ferramenta SUPERSYS_HCDCR (registrada como software livre) desenvolvida, implementada e validada nos cultivos realizados, desempenha as funcoes basicas de softwares de supervisao de biorreatores, tais como: monitoramento e aquisicao de dados de pressao, temperatura, pH, COD, fracao de CO2 e de O2 nos gases de saida; estimativa em tempo real do quociente respiratorio, das velocidades de consumo de oxigenio e de producao de CO2. Esta ferramenta apresenta as seguintes funcionalidades especiais: i) controle automatico das vazoes de ar e de oxigenio de acordo com a demanda celular; ii) acionamento automatico da bomba de alimentacao ao final da batelada; iii) controle automatico da vazao de alimentacao em funcao da velocidade especifica de crescimento inferida em tempo real; iv) controle automatico da alimentacao com restricoes pela concentracao de oxigenio dissolvido; v) alarmes sonoros indicando falhas no processo; vi) envio de mensagens de falhas por email; vii) controle automatico da concentracao de oxigenio dissolvido; viii) controle de seguranca da pressao do biorreator, e ix) controle da temperatura do banho. Em relacao aos estudos das estrategias de alimentacao visando ao aumento da produtividade em biomassa em cultivos de alta densidade celular de E. coli recombinante, com o auxilio da ferramenta de supervisao desenvolvida aliada a modificacoes na composicao do meio de cultivo sintetico disponivel na literatura, foram alcancadas concentracoes celulares maiores que 150 g/L em menos de 24 h de tempo total de cultivo, levando a uma produtividade de 9,2 g/Lh, a qual e superior aos valores relatados na literatura, sem acumulo de acetato e possibilitando elevada producao da proteina recombinante.

The proposal focuses on phasing scenario and identify how to treat the monument intact, but she fully exploit the current way. These phases are hierarchically established, without continuing into the next stage. Because the mill building to respond flexibly to the specific needs of communities. The concept is based on the gradual additive laminate and function. Layering and arise solely the premises, but also the interconnections, which between them generate more interaction. Each material has its own particular character and its own hierarchy towards other functional masses.

Das wesentliche Ziel dieser Doktorarbeit ist es, die Zusammenhänge zwischen der Struktur von kleinen organischen Molekülen, deren Anordnung in der Dünnschicht und der Effizienz organischer Solarzellen zu beleuchten. Die Kombination der komplementären Methoden spektroskopischer Ellipsometrie (VASE) und Röntgenstreuung, vor allem der unter streifendem Einfall (GIXRD), hat sich als sehr effiient für die Strukturuntersuchungen organischer Dünnschichten erwiesen. Zusammen geben sie einen detailreichen Einblick in die intermolekulare Anordnung, die Kristallinität, die molekulare Orientierung, die optischen Konstanten n und k und die Phasenseparation von organischen Schichten. Zusätzlich wird die Topografie der organischen Dünnschicht mit Rasterkraftmikroskopie untersucht. Der erste Fokus liegt auf der Analyse des Dünnschichtwachstums von Zink-Phthalocyanin (ZnPc) Einzelschichten. Für alle untersuchten Schichtdicken (5, 10, 25, 50 nm) und Substrattemperaturen (Tsub=30°C, 60°C, 90°C) zeigt ZnPc ein kristallines Schichtwachstum mit aufrecht stehenden ZnPc Molekülen. Um effiziente organische Solarzellen herzustellen, werden Donor- und Akzeptormoleküle üblicherweise koverdampft. Bei der Mischung von Donor- und Akzeptormolekülen bildet sich eine gewisse Phasenseparation aus, deren Form wesentlich für die Ladungsträgerextraktion entlang der Perkolationpfade ist. Der Ursprung dieser Phasenseparation wird innerhalb dieser Arbeit experimentell für ZnPc:C60 Absorber-Mischschichten untersucht. Um die Ausprägung der Phasenseparation zu variieren, werden verschiedene Tsub (30°C, 100°C, 140°C) und Mischverhältnisse (6:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:6) bei der Koverdampfung von ZnPc und C60 angewendet. GIXRD Messungen zeigen, dass hier der bevorzugte Kristallisationsprozess von C60 Molekülen die treibende Kraft für eine effiziente Phasenseparation ist. Solarzellen, die ZnPc:C60 Mischschichten mit verbesserter Phasenseparation enthalten (Tsub=140°C, 1:1), zeigen eine verbesserte Ladungsträgerextraktion und somit eine höhere Effizienz von 3,0% im Vergleich zu 2,5% für die entsprechende Referenzsolarzelle (Tsub=30°C, 1:1). Im zweiten Teil der Arbeit wird der Einfluss der Molekülorientierung auf die Dünnschichtabsorption beispielhaft an ZnPc und Diindenoperylen (DIP) untersucht. DIP und ZnPc Moleküle, die auf schwach wechselwirkenden Substraten wie Glas, SiO2, amorphen organischen Transportschichten oder C60 aufgedampft sind, zeigen eine eher stehende Orientierung innerhalb der Dünnschicht in Bezug zur Substratoberfläche. Im Gegensatz dazu führt die Abscheidung auf stark wechselwirkenden Substraten, wie z.B. einer Gold- oder Silberschicht oder 0.5 nm bis 2 nm dünnen PTCDA (3,4,9,10-Perylentetracarbonsäuredianhydrid) Templatschichten laut GIXRD und VASE Messungen dazu, dass sich die ZnPc und DIP Moleküle eher flach liegend orientieren. Dies führt zu einer wesentlich besseren Dünnschichtabsorption da das molekulare Übergangsdipolmoment jeweils innerhalb der Ebene des ZnPc und des DIP Moleküls liegt. Ein Einbetten von Gold- oder Silberzwischenschichten in organischen Solarzellen führt leider zu keinen klaren Abhängigkeiten, da die verbesserte Absorption durch die flach liegenden Moleküle von Mikrokavitäts- und plasmonischen Effekten überlagert wird. Ebenso wenig führte das Einfügen einer PTCDA-Zwischenschicht in organischen Solarzellen zum Erfolg, da hier Transportbarrieren den Effekt der verbesserten Absorption überlagern. Das letzte Kapitel konzentriert sich auf den Einfluss der Molekülstruktur auf das Dünnschichtwachstum am Beispiel von DIP und dessen Derivaten Ph4-DIP und P4-Ph4-DIP, Isoviolanthron und Bis-nFl-NTCDI (N,N-Bis(fluorene-2-yl)-naphthalenetetra-carboxylic Diimid) Derivaten. GIXRD Messungen belegen deutlich, dass die sterischen Behinderungen, hervorgerufen durch die Phenylringe (für Ph4-DIP und P4-Ph4-DIP) und Seitenketten (für Bis-nFl-NTCDI), ein amorphes Schichtwachstum induzieren. Im Vergleich sind die Dünnschichten von DIP und Bis-HFl-NTCDI kristallin. Bezüglich der Molekülorientierung und folglich der Absorption von DIP und dessen Derivaten kann ein starker Einfluss des Schichtwachstums beobachtet werden. In Solarzellen verhindert die Präsenz der Phenylringe eine effiziente Phasenseparation der Mischschichten aus (P4-)Ph4-DIP:C60, was zu einer verschlechterten Ladungsträgerextraktion und damit zu einem reduzierten Füllfaktor (FF) von 52% im Vergleich zu dem entsprechender DIP:C60 Solarzellen mit FF=62% führt Die Untersuchungen an der Bis-nFl-NTICDI Serie zeigen ein ähnliches Ergebnis: Auch hier zeichnen sich die amorphen Schichten aus Bis-nFl-NTCDI Molekülen mit Seitenketten durch schlechtere Transporteigenschaften aus als nanokristalline Bis-HFl-NTCDI Schichten. / The aim of this thesis is to demonstrate correlations between the molecular structure of small organic molecules, their arrangement in thin films, and the solar cell performance. For structure analysis of the organic thin films, the combination of variable angle spectroscopic ellipsometry (VASE) and grazing incidence X-ray diffraction (GIXRD) as complementary methods turned out to be a powerful combination. Using both methods, it is possible to obtain information about the crystallinity, crystallite size, intermolecular arrangement, mean molecular orientation, optical constants n and k, and phase separation within thin films. In addition, the topography of thin films is analyzed by atomic force microscopy. First, the thin film morphology of pristine zinc-phthalocyanine (ZnPc) films deposited at different substrate temperatures (Tsub=30°C, 60°C, 90°C) and for varying film thicknesses (5, 10, 25, 50 nm) is investigated. The ZnPc films grow highly crystalline with an upright standing molecular orientation with respect to the substrate surface for all investigated Tsub and all film thicknesses. In effcient organic solar cells, donor and acceptor molecules are commonly co-deposited to form a blend absorber film. This is usually accompanied by a certain phase separation between donor and acceptor molecules leads to a formation of percolation paths necessary to extract electrons and holes towards the electrodes. For ZnPc:C60 blends the origin of this phase separation process is analyzed by investigating different degrees of phase separation induced by film deposition at different Tsub (30°C, 100°C, 140°C) and for different blend ratios (6:1, ... , 1:6 (vol%)). GIXRD measurements indicate that the preferred crystallization of C60 is the driving force for good phase separation. Solar cells with improved phase separation of ZnPc:C60 blends (Tsub=140°C, 1:1) reveal a better charge carrier extraction and thus enhanced effciencies of 3.0% in comparison to 2.5% for the reference device (Tsub=30°C, 1:1). In the second part, the impact of molecular orientation within the absorber thin films on light harvesting is examined for pristine ZnPc and diindenoperylene (DIP) films. For film deposition on weakly interacting substrates like glass, SiO2, amorphous organic transport films, or C60, the orientation of DIP and ZnPc molecules is found to be upright standing. In contrast, GIXRD and VASE measurements show that films deposited onto strongly interacting substrates like Au and Ag, as well as on thin PTCDA templating layers lead to nearly flat-lying ZnPc and DIP molecules. Since the molecular transition dipole moment is oriented in the plane of the DIP and ZnPc molecules, the light absorption in films with flat-lying molecules is strongly improved. Unfortunately, an implementation of Au or Ag sublayers in organic solar cells does not result in reliable dependencies since the enhanced absorption by an improved molecular orientation is superimposed by different effects like microcavity and plasmonic effects. The implementation of PTCDA interlayers leads to transport barriers making the solar cell data interpretation difficult. In the last part, the influence of molecular structure on thin film growth is studied for DIP and its derivatives Ph4-DIP and P4-Ph4-DIP, isoviolanthrone, and Bis-nFl-NTCDI derivatives. GIXRD measurements reveal that steric hindrance is induced by the addition of side chains (for Bis-nFl-NTCDI) and phenyl rings (for Ph4-DIP and P4-Ph4-DIP) (N,N-Bis(fluorene-2-yl)-naphthalenetetra-carboxylic diimide) leading to an amorphous thin film growth. In contrast, DIP films and Bis-HFl-NTCDI films are found to be crystalline. The mean molecular orientation and hence the absorption is strongly affected by the different growth modes of DIP and its derivatives. In OSC, the presence of the phenyl rings prevents an effcient phase separation for (P4-)Ph4-DIP:C60 blends which causes diminished charge extraction in comparison to the crystalline DIP:C60 blends. For the Bis-nFl-NTCDI series, the transport properties are significantly worse in the amorphous films composed of Bis-nFl-NTCDI derivatives with alkyl chains in comparison to the nanocrystalline films made of the bare Bis-HFl-NTCDI.