Strategic release planning (road-mapping) is an important phase of requirements engineering process performed at product level. It is concerned with selection and assignment of requirements in sequences of releases such that important technical and resource constraints are fulfilled. It is always considered difficult to form a strategic release plan due to varying constraints and uncertainties. In this regard, different strategic release planning models have been presented in academia and different methods are being used in Industry. In this thesis, strategic release planning models presented in academia and some methods of strategic release planning being used in Industry are identified. The contributions of these models are also provided in the thesis. A systematic review has been performed to know strategic release planning models in academia. The aim of systematic review is to present fair evaluation of research concerning strategic release planning models. Through systematic review, requirements selection factors considered by a model, validation details of model and a model’s usefulness for bespoke and market-driven development are summarized. Moreover two organizations have been interviewed to know strategic release planning models being used in Industry in addition to the ones presented in academia. Similarly contribution of models being used in Industry is provided by logging details of requirements selection factors, validation details and usefulness for bespoke and market-driven software development of each model / process of Industry. Based on systematic review and industrial interviews’ results, a list of common requirements selection factors (considered by models of academia and Industry) is provided. Some general recommendations have been given for research in academia on strategic release planning models after analysis of systematic review and industrial interviews’ results. / Strategisk release planering (väg-kartläggning) är en viktig fas av requirements engineering process som utförs på produktnivå. Det handlar om urval och tilldelning av kraven i sekvenser av utsläpp så att viktiga tekniska och resurser är uppfyllda. Det är alltid anses svårt att skapa en strategisk release planen på grund av olika begränsningar och osäkerheter. I detta avseende olika strategiska release planering modeller har presenterats i den akademiska världen och olika metoder som används inom industrin. I denna avhandling, strategisk release planering modeller i den akademiska världen och vissa metoder för strategisk release planering som används inom industrin har identifierats. Bidraget från dessa modeller är också i avhandlingen. En systematisk genomgång har gjorts att veta strategisk release planering modeller i den akademiska världen. Syftet med systematisk översyn är att presentera en rättvis utvärdering av forskning om strategisk release planering modeller. Genom systematisk genomgång, krav urval faktorer betraktas som en modell, validering uppgifter om modell och en modell nyttan för beställda och marknadsdriven utveckling sammanfattas. Dessutom två organisationer som har intervjuats att veta strategisk release planering modeller som används inom industrin och utöver de åtgärder som presenteras i den akademiska världen. Likaså bidrag av modeller som används inom industrin ges genom att logga information om kraven urval faktorer, validering information och nytta för den beställda och marknadsdrivna mjukvaruutvecklingen av varje modell/process industri. Baserat på systematisk genomgång och industriell intervjuer resultat, en förteckning över gemensamma krav urval faktorer (som av modeller av den akademiska världen och industrin) tillhandahålls. Några allmänna rekommendationer har fått för forskning i den akademiska världen på strategisk release planering modeller efter analys av systematisk översyn och industriell intervjuer resultat. / +46765541016, +46762920070

Problem behavior is a concern for individuals with developmental disabilities. Research suggests that a release contingency time-out is effective to reduce problem behavior, but may increase the duration of time-out. Other sources recommend including a release contingency to avoid reinforcing problem behavior. It is possible clinicians generalize this concept to other domains, such as differential reinforcement with discrete-trial-training. Such a modification may be conceptualized as a tandem ratio requirement. Evidence from basic literature suggests that a tandem ratio requirement may increase a bout of responding. The current study examined effects of applied behavior analytic procedures using a bout analysis. The purpose was to identify a best-practice recommendation for clinicians to use when patterns of bout-like responding are evident, in order to efficiently decrease the duration of a bout. Three children with ASD participated. Results showed that release contingencies influenced bout-like responding in two participants. Social validity was assessed on the feasibility, efficacy, and likeability of the study. Social validity measures indicated the study had appreciable effects on problem behavior.

The purpose of the thesis is to conduct a case study for investigating change and release management at Catella Bank, within the context of IT Service Management (ITSM), by measuring and to provide suggestions for improvements. Incident and operations management is included to enhance the understanding of the historical performance at Catella. The case study is set out to answer the following research questions: 1. “How does a transition in change management structure impact the performance of successfully delivering both changes and releases of IT services at a financial institution?” 2. “What are the causes of delays in the delivering changes and releases?” 3. “How does stakeholder involvement alter the performance of implementing a successful change and release?” 4. “How do Information Technology, and the corresponding departments manage and control necessary changes and releases of software at present?” Research methodology utilized in the thesis includes both qualitative and quantitative research, including interviews, participation in meetings and empirical investigation of internal material at Catella. The result from the research has provided a significant collection of issues, as well as suggested solutions for Catella to take to improve organizational maturity in enhancing the capabilities in performing work related to the four managerial disciplines within ITSM. The research culminated in the creation of the CHARM (CHange And Release Management) model, which consists of integrating change and release management into project management, split between three different components for the three organizational levels. The author has created the following components: Strategy matrix, a governance model, and a process model.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第15675号 / 工博第3333号 / 新制||工||1503(附属図書館) / 28212 / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 森 泰生, 教授 跡見 晴幸, 教授 濵地 格 / 学位規則第4条第1項該当

Les gradients de concentration de peptides ou de protéines, ou leur relargage localisé, jouent un rôle primordial dans les voies de communication inter-cellulaire. L'activation locale de cellules est étudiée in vitro à l'aide de sources artificielles contraignantes ou invasives de protéines (pipettes, dispositifs microfluidiques). Des méthodes plus douces et moins invasives sont très demandées. À cet effet, nous avons développé deux types de capsules capables de libérer des macromolécules sous l'effet d'une stimulation extérieure. Le premier système emploie des liposomes additionnés d'un amphiphile à azobenzène, tensioactif ou polyélectrolyte, capable de générer des pores à travers la membrane sous l'effet de la lumière. Les temps de dissolution des assemblages lipides/tensioactifs et les cinétiques de relargage (perméabilité) sous irradiation lumineuse ont été étudiées par diffusion dynamique de la lumière et fluorescence. Le second système repose sur des capsules à cœur aqueux et à coque polymère, formées par polyaddition interfaciale. Nous avons montré que l'inclusion de chaînes thermosensibles dans la membrane (polyNIPAM, par ex.) rendait la stabilité de la capsule dépendante de la température. Nous avons démontré sur des capsules millimétriques, chargées avec du dextrane ou des protéines, que cela permettait le contrôle du relargage. L'utilisation de polymère à UCST en milieu aqueux nous a permis d'obtenir les premières capsules thermosensibles capables de libérer leur contenu par élévation de la température au dessus d'une valeur critique. Cela ouvre une voie prometteuse au développement d'un système biocompatible de libération de protéines. / Concentration gradients and local delivery of peptides or proteins play a crucial role in intercellular communication. In vitro, the effects of local activation of cells are studied with constrained or invasive artificial protein sources (pipettes, microfluidics). Milder and remotely-triggered techniques for the release of encapsulated biomolecules are highly in demand. To this aim we developed two classes of capsules able to release macromolecules upon an external stimulation. The first system is based on liposomes sensitized with azobenzene-containing amphiphiles (surfactants or polyelectrolytes) that can open pores in the membrane upon exposure to light. The dissolution time of lipids/surfactants assemblies and rate of release (permeability) under light irradiation has been assessed by dynamic light scattering and fluorescence measurements. The second system is a model of capsules with an aqueous core and a polymer shell, formed by interfacial polyaddition. We showed that inclusion of temperature-responsive chains in the membrane, e.g. polyNIPAM, confers temperature-dependant stability to the capsules; we demonstrated with millimeter-sized capsules loaded with dextran or proteins that this can be used to trigger the release. Using chains with UCST in water, we obtained the first temperature-sensitive capsules able to release their content upon increasing the temperature above a threshold. This represents a promising route to the biocompatible delivery of proteins.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: doc. RNDr. Milan Dittrich, CSc. Student: Marie Křivková Title of Thesis: Modification of parameters of nanoparticles prepared from aliphatic hydroxyacids polyesters Polyesters of aliphatic α-hydroxyacids are mentioned in the theoretical part. A significant part of it is mostly devoted to the polyester PLGA. Physicochemical properties, the process of biodegradation and biodistribution are described there. Subsequently, some examples of PLGA utilization in pharmacy and medicine are mentioned. The theoretical part deals also with the method of diffusion used for nanoparticles preparation, which was used in the experimental part, and the principles of size and surface charge measurements of these nanoparticles. The crucial part of this master thesis is based upon an experiment. It is focused on various approaches to the formulation of nanoparticles out of aliphatic polyester carriers with variable molecular constitution. Polymer PLGA with linear molecule and polymers containing PLGA branched on tripentaerythritol and polyacrylic acid were used. Using the diffusion method, nanoparticles were prepared out of these carriers. The outer water-based phase was modified by use of cetrimide of different...

Doctor of Philosophy / Department of Horticulture and Natural Resources / Dale J. Bremer / Turfgrasses sequester and emit carbon dioxide, and emit nitrous oxide (N₂O) when fertilized with nitrogen and irrigated. Future water availability is a serious issue and drought restrictions may be imposed on turf managers while turf areas are subjected to traffic stress. My objectives in Chapter 2 were to: 1) quantify the magnitude and patterns of N₂O emissions and carbon (C) sequestration in zoysiagrass (Zoysia japonica Steud.); and 2) determine how irrigation (66% and 33% reference evapotranspiration [ET₀] replacement) and fertilization (polymer-coated urea, urea, and unfertilized) management may reduce N₂O emissions and enhance carbon sequestration. My objectives in Chapters 3 and 4 were to evaluate above- and below-ground responses of cool-season (C3) [Kentucky bluegrass (Poa pratensis L.) and perennial ryegrass (Lolium perenne L.)] and warm-season (C4) grasses {buffalograss [Buchloe dactyloides (Nutt.) Engelm] and zoysiagrass] at golf course-related mowing heights [1.6-cm (fairway) and 6.4-cm (rough)], with and without traffic during a simulated drought and subsequent recovery period (without traffic). In Chapter 2, N₂O emissions increased by 6.3% with more irrigation during summers and increased from 4.06 kg ha⁻¹ in unfertilized turf to 4.50, and 5.62 kg ha⁻¹ in polymer-coated urea and urea treated turf, respectively, during the 2-year study. There was no difference in C sequestration rates between a high vs. low input management schedule. The C sequestration rate was 0.952 Mg C ha⁻¹ yr⁻¹ for zoysiagrass when averaged across management schedules and depths. The use of a controlled-release fertilizer such as PCU compared to the use of a quick-release fertilizer and/or lower irrigation will reduce N₂O emissions in turfgrass. In Chapters 3 and 4, the better drought tolerance of C4 grasses led to more differences between traffic treatments within C4 than C3 grasses, but C4 grasses maintained the highest quality and green cover. Quality at rough- compared to fairway-height was more impacted by traffic. Decreasing soil moisture due to drought led to a minimal impact from traffic on soil bulk density, soil penetration resistance (SPR), and root measurements. During drought, SPR at deeper soil depths and fairway plots increased and exceeded the critical value of 2.0 MPa. Both C4 grasses and perennial ryegrass had larger root diameters, which may have led to better soil compaction resistance. Traffic during drought will have a negative and accelerated impacts above-ground, but minimal impact below-ground, which will vary with turf species and mowing height.

M.A. / Please refer to full text to view abstract

L'intérêt pour le développement de ciments osseux à base de phosphates de calcium (CaP) en tant que systèmes de délivrance de médicament a augmenté en raison de sa capacité à être injecté et à permettre un traitement local et contrôlé des maladies ou défauts osseux. A cette fin, nous nous sommes intéressés à la formulation d’un ciment mixte à base de carbonate et phosphate de calcium (CaCO3-CaP) chargé avec différentes teneurs (3, 6 et 9% calculé par rapport à la masse de la phase solide du ciment) en acide fusidique (AF), composé pratiquement insoluble dans l’eau, ou en son sel hydrosoluble, le fusidate de sodium (SF). L’influence de l’incorporation de l’antibiotique sous ces deux formes sur les propriétés physicochimiques (temps et cinétique de prise, résistance à la compression, injectabilité) et la microstructure (porosité) du ciment ainsi que sur la libération in vitro de ce médicament a été étudiée. L’effet de la quantité d’eau (rapport liquide/solide (L/S)) utilisée pour l’élaboration du ciment sur ces propriétés a été également examiné. Les résultats obtenus ont révélé que l'ajout de l’antibiotique n’avait aucun effet sur la composition minérale du ciment durcit : la réaction de prise donne lieu à la formation d’une apatite carbonatée analogue au minéral osseux. Nous avons observé que le temps de prise du ciment a été prolongé par l’addition d’AF, tandis que la présence de SF le réduit et cet effet est dose dépendant. L’utilisation d’un accélérateur de prise (Na2HPO4) réduit le temps de prise d’une manière significative, et a permis d’atteindre un temps de prise de l’ordre de 25 à 30 minutes ; celui-ci se situe dans une gamme compatible avec une application en chirurgie orthopédique ou dentaire. Ce travail a également permis de mettre en évidence que l’incorporation de l’antibiotique dans le ciment s’accompagne d’ une diminution de la porosité et de la résistance à la compression. En outre, l’augmentation du rapport liquide-solide (L/S) se traduit par une augmentation du temps de prise, de la porosité des ciments et par une diminution de la résistance à la compression. Les mesures d’injectabilité des ciments étudiés ont montré que la charge nécessaire pour l’extrusion de la pâte est diminuée par l'ajout d’AF (injectabilité améliorée) et que cet effet est amplifié en présence de SF. Le phénomène de séparation de phases qui limitait l’injectabilité de la pâte du ciment de référence a été supprimé par l’ajout de 9 % de SF et par l’augmentation de la quantité d’eau utilisée (L/S plus élevé) pour l’élaboration du ciment. Les essais de libération in vitro du principe actif dans une solution de NaCl 0.9 % à 37°C pendant un mois montrent que la libération est prolongée et ce quels que soient la forme de l’antibiotique et le rapport L/S. Le taux libéré est lié à la porosité totale et à la taille des pores du ciment ainsi qu’à la solubilité de l'antibiotique. Les quantités libérées par jour sont de l’ordre de 0.5 à 2 mg/L. La libération du médicament a été modélisée en utilisant les équations de Korsmeyer-Peppas, de Higuchi ou de Kopcha. Les résultats ont montré que la libération du médicament est contrôlée principalement par un mécanisme de diffusion. Enfin, l’efficacité in vitro du système de délivrance préparé a été évaluée à travers des essais microbiologiques réalisés avec les ciments chargés en antibiotique ; les résultats préliminaires obtenus ont montré une activité anti-biofilm faible sur la souche bactérienne de type Staphylococcus aureus. / The interest in developing calcium phosphate cements as a drug delivery system has risen because of its capability to be injectable and to enable local and controlled treatment of bone disease or defects. In the present work, we are interested in the development of a mixed cement based on calcium phosphate and carbonate (CaCO3-CaP) loaded with different concentrations (3, 6 and 9% calculated on the weight of the cement solid phase) of fusidic acid (FA) compound substantially insoluble in water, or its water soluble salt, sodium fusidate (SF). The influence of the incorporation of both forms of antibiotic on the physicochemical properties (setting time and setting reaction kinetics, compressive strength, injectability) and the microstructure (porosity) of the cement as well as on the in vitro release of this drug was studied. The effect of the amount of water (liquid / solid ratio (L / S)) used for the preparation of cement on these properties was also examined. The results obtained showed that the addition of the antibiotic had no effect on the final composition of the hardened cement: the setting reaction leads to the formation of a carbonated apatite analogous to bone mineral. The setting time of the cement was prolonged by the addition of AF, while it is reduced in the presence of SF and we showed that this effect is dose-dependent. The introduction of an accelerator (Na2HPO4) in the cement formulation reduces the setting time significantly in a range (25 to 30 minutes) which is adapted to orthopedic and dental applications. This work has also demonstrated that the incorporation of the antibiotic in the cement is accompanied by a decrease in the cement porosity and resistance to compression. In addition, increasing the liquid to solid ratio induced an increase in the setting time and in the porosity of the cement whereas the cement compressive strength is decreased. Measurements conducted on cement injectability have shown that the load required to extrude the paste is reduced by the addition of AF (improved injectability) and this effect is enhanced in the presence of SF. The phase separation phenomenon that limits the injectability of the reference cement paste was suppressed by the addition of 9% of SF and by increasing the amount of water (higher L / S) used for the preparation of cement. In vitro release test of the antibiotic in NaCl 0.9% solution at 37 °C over one month showed that the release is sustained regardless of the form of the antibiotic and of the L / S ratio. The released rate is related to the total porosity and pore size of the cement as well as the solubility of the antibiotic. The amounts released per day are in the range of 0.5 to 2 mg /L. Drug release was modeled using the Korsmeyer-Peppas, Higuchi or Kopcha equations. These modelisations showed that the drug release is mainly controlled by a diffusion mechanism. Finally, the in vitro efficiency of the prepared drug delivery systems was evaluated through microbiological tests on antibiotic-loaded cements; the preliminary results obtained showed a weak anti-biofilm activity against Staphylococcus aureus bacterial strain.

Les thérapeutiques individualisées et ciblées se développent actuellement, les formes galéniques évoluent donc en parallèle pour contrôler la libération des principes actifs (PA) et les conduire au plus proche des sites d’intérêts. Les formes orales solides représentent les formulations galéniques les plus utilisées, faciles d’emploi, indolores et réduisant le risque d’infection. Lors de leur conception, il est aussi possible de moduler la libération du PA.Deux approches sont étudiées dans ce manuscrit, l’une correspond au ciblage de la libération d’un PA vers son site d’action thérapeutique qui est le colon, la seconde consiste à contrôler la libération du PA pour maintenir une concentration constante, minimiser les effets indésirables et les périodes de présence de concentrations sub-thérapeutiques au niveau du site d’action.Première approche :Les traitements des Maladies Inflammatoires Chroniques de l’Intestin (MICI) peuvent être significativement améliorées par une libération localisée du PA. Une des approches est l’utilisation d’enrobages composés de polysaccharides dégradés par les enzymes sécrétées par la microflore colique. Mais l’absence d’une méthode in vitro reproductible simulant les conditions physiologiques du colon et l’impact potentiel des traitements antibiotiques associées qui pourraient affecter la quantité et la qualité des bactéries présentes et des enzymes sécrétées est un obstacle à sa mise au point. L’objectif de l’étude était d’effectuer un screening de polysaccharides ayant un intérêt dans le développement de nouvelles formulations à libération colique. Après cette sélection, la libération des formulations retenues ont été évaluées par une méthode utilisant des selles de patients atteints de MICI traités ou non par antibiothérapie. Enfin, l’utilisation de mélanges bactériens pour un éventuel remplacement de l’utilisation de selles fraiches a été évaluée.Seconde approche : Les formes orales enrobées présentent un grand potentiel pour la libération contrôlée de PA. Néanmoins, il est difficile d’obtenir une libération à vitesse constante avec ce type de formulation. Ceci est généralement dû au rôle prédominant du transport de masse par diffusion, ce qui entraine, avec le temps, une diminution de la concentration en PA au cœur du système, donc une réduction du gradient de concentration qui est la force motrice de la libération du PA. Ce type de cinétique de libération peut être inapproprié pour un traitement médicamenteux sûr et efficace. Malgré l’importance pratique de ce défi crucial de formulation, étonnamment, peu de stratégies efficaces sont connues. Dans cette étude, une nouvelle approche, basée sur une succession de couches de PA et de polymères (initialement dépourvu de PA) présentant une distribution initiale de PA non homogène, associé à un effet de temps de latence et à une diffusion partielle initiale à travers le noyau de la minigranule. Des variations de type, de quantité, d’épaisseur et de séquence des couches de PA et de polymères ont été testées. Un système assez simple composé de quatre couches (deux couches de PA et deux couches de polymère) permettait d’aboutir à une libération relativement constante durant 8h. / Individualized and targeted therapies are currently developed, therefore the dosage forms move in parallel to control the drug release and drive it nearest to interest sites. Solid oral dosage forms are the pharmaceutical formulations the most common, easy to use, painless and reducing the infectious risk. In these formulation designs, it is also possible to adjust the drug release.Two approaches are discussed in this manuscript, the first one targets the drug release to the therapeutic site of action which is the colon, and the second one consists on controlling the drug release to maintain a constant concentration, minimize side effects and periods of presence of sub-therapeutic concentrations at the site of action.The first approach:The treatment of colonic disease like Inflammatory Bowel Diseases (IBD), can be significantly improved via local drug delivery. One approach is to use polysaccharide coatings, which are degraded by enzymes secreted by the colonic microflora. However, the lack of a reliable in vitro test simulating conditions in a living colon and the potential impact of associated antibiotic treatments that could affect the quality and quantity of bacteria and enzymes secreted is an obstacle to its development. The aim of the study was to perform a screening of polysaccharides suitable for the development of new colonic release formulations. After this selection, the drug release of selected formulations were evaluated by a method using the stools of IBD patients treated or not with antibiotics. Finally, the use of bacterial mixtures substituting fresh fecal samples has been evaluated.The second approach: Coated pellets offer a great potential for controlling drug delivery systems. However, constant drug release rates are difficult to achieve with this type of dosage forms if the drug is freely water-soluble. This is because diffusional mass transport generally plays a major role and with time the drug concentration within the system decreases, resulting in decreased concentration gradients, which are the driving forces for drug release. This type of release kinetics might be inappropriate for an efficient and safe drug treatment. Despite the great practical importance of this potentially crucial formulation challenge, surprisingly little is yet known about efficient formulations. In this study, a novel approach is presented based on sequential layers of drug and polymer (initially free of drug) to provide a non-homogeneous initial drug distribution, combined with lag-time effects and partial initial drug diffusion towards the pellet’s core. By changing the type, number, thickness and sequence of the drug and polymer layers, a rather simple 4 layers system (2 drug and 2 polymer layers) allowed an about constant drug release during 8 h.