Ce travail porte sur la mise au point des nanocochléates intégrant à la fois l’amphotéricine B (AmB) et la miltéfosine (hexadécylphosphocholine, HePC) dotés de propriétés adéquates pour une administration par voie orale pour le traitement de la leishmaniose viscérale. Notre premier axe de recherche a été l’étude des interactions de l’AmB et de l’HePC avec les monocouches de lipides de DOPS (dioleoyl phosphatidylsérine) et de Cho (cholestérol) dans le développement de nanocochléates chargés avec ces deux principes actifs. Les résultats expérimentaux nous ont permis de déterminer le rapport drogue/lipides optimal pour la formulation des nanocochléates : 9DOPS/1Cho/0,5AmB/0,5HePC et de confirmer que dans la formulation de nanocochléates, l’AmB et l’HePC sont incorporés de façon stable et se situent au sein des bicouches lipidiques entre des lipides, plutôt que dans la phase aqueuse entre les bicouches.Notre second axe de recherche a porté sur la formulation et la caractérisation des nanocochléates chargés en AmB et en HePC. Ces nanocochléates ont été formulés à partir des liposomes unilamellaires encapsulant ces deux principes actifs. Les paramètres expérimentaux majeurs (taille de liposomes, proportion DOPS/1Cho) ont été optimisés. Les propriétés physico-chimiques des nanocochléates, telles que la taille, la charge de surface, la morphologie, le rendement d'encapsulation, l’organisation des principes actifs et la stabilité pendant le stockage au cours de temps ont été étudiées. En vue d'une formulation orale, la libération des principes actifs in vitro ainsi que la stabilité des nanocochléates in vitro dans les milieux gastro-intestinaux ont également été étudiés d’après la Pharmacopée des Etats-Unis. Enfin, une étude in vivo préliminaire chez le rat portant sur la pharmacocinétique plasmatique d'AmB après administration orale de nanocochléates chargés en AmB avec ou sans HePC en comparaison avec l’Ambisome® et la Fungizone® a été entamée. Les résultats préliminaires ont démontré une absorption significative par voie orale de l’AmB.Ce travail a permis de développer des nanocochléates avec des propriétés appropriées pour une formulation contenant à la fois l’AmB et l’HePC administrable par voie orale. Néanmoins, des optimisations restent à réaliser avant d’envisager une application clinique. / The aim of this work was to formulate nanocochleates containing both Amphotericin B (AmB) and miltefosine (hexadecylphosphocholine, HePC) with properties suitable for administration by the oral route for the treatment of visceral leishmaniasis. The first part of this work was a fundamental study of the interactions between AmB and HePC and monolayers of dioleylphosphatidylserine (DOPS) with or without cholesterol (Cho), to provide a basis for the formulation of nanocochleates containing the two active molecules. The results allowed us to define the optimal proportions for the formulation of nanocochleates: 9DOPS/1Cho/0.5AmB/0.5HePC and to predict that AmB and HePC would be incorporated stably into the formulation and would be located between the lipids in the bilayers rather than in the aqueous phase between the bilayers. The second part of the work was the formulation and characterization of nanococheates containing both AmB and HePC. These were derived from unilamellar liposomes containing the two active molecules. The crucial experimental parameters (size of the liposomes, ratio of DOPS to Cho) were optimized. The physico-chemical properties of the nanocochleates, such as the size, surface charge, morphology, encapsulation yield, the organization of the active molecules and the stability during long-term storage were studied. Since the formulation was destined for the oral route, in-vitro drug release and the stability of the nanocochleates in simulated gastro-intestinal media were studied according to the recommendations of the US Pharmacopeia. Finally, a preliminary in-vivo study of the plasma pharmacokinetics of AmB after oral gavage to rats of nanocochleates contained AmB with or without HePC, in comparison with AmBisome and Fungizone, was carried out. A significant oral absorption of AmB was observed. This work has led to the formulation of nanocochleates containing AmB and HePC with appropriate properties for oral administration. However, further optimization is necessary before such particles will be suitable for clinical use.

Effects of route choice by Advanced Traveller Information Service (ATIS) were investigated in a study. To support the route choice behavior, the possibility of using collective traffic management systems which are mounted in public road space. To investigate what factors and what information must be communicated to the driver so that they change their route. In this work ATIS be examined in city traffic. The empirical study will verify what the role of ATIS is and which characteristics of the Information Service influence the decision strat-egy. Variable Message Signs will inform the driver while driving on possible alternatives and issues that have a major impact on the driver\\\'s decision. Here, the driver does not always make a decision within the meaning of homo oeconomicus, which increases the subjective benefits. But other determinants such as socio-demographic variables interacts with decision.

Inefficient road transportation causes unnecessary costs and polluting emissions. This problem is even more severe in refrigerated transportation, in which temperature control is used to guarantee the quality of the products. Organizing logistics cooperatively can help decrease both the environmental and the economic impacts. In Joint Route Planning (JRP) cooperation, suppliers and customers jointly optimize routing decisions so that cost and emissions are minimized. Vendor Managed Inventory (VMI) cooperation extends JRP cooperation by optimizing routing and inventory planning decisions simultaneously. However, in addition to their economic advantages, VMI and JRP may also yield environmental benefits. To test this assertion, we perform a case study on cooperation between a number of supermarket chains in the Netherlands. The data of this case study are analyzed to quantify both the economic and environmental benefits of implementing cooperation via JRP and VMI, using vehicle routing and an inventory routing models. We found that JRP cooperation can substantially reduce cost and emissions compared with uncooperative routing. In addition, VMI cooperation can further reduce cost and emissions, but minimizing cost and minimizing emissions no longer result in the same solution and there is a trade-off to be made.

Routing hijacks have plagued the Internet for decades. These attacks corrupt the routing table entries that networks use to forward traffic, causing affected network devices to route private and possibly sensitive Internet traffic towards the hijacker. Despite many failed attempts to thwart hijackers, recent Internet-wide routing monitoring infrastructures give us hope that future systems can quickly and ultimately mitigate hijacks. Such monitoring infrastructures consist of multiple globally distributed monitoring entities, called Route Collectors. To enable the whole community to monitor the validity and stability of the exchanged routing information, network volunteers disclose their routes to public route collectors. However, hijackers can also exploit this information to avoid being reported to route collectors. This thesis evaluates the effectiveness of monitoring infrastructures against two kinds of hijack scenarios: (i) an omniscient attacker with complete knowledge of both the Internet topology and the routing preferences of networks, and (ii) a realistic attacker which lacks such knowledge but gathers routing information from what networks themselves disclose to the public route collectors. Prior simulations showed that hijacks that affect more than 2% of the Internet are always visible to the public route collector infrastructure. However, our simulations show that omniscient and realistic hijackers that react to the deployment of public collectors could stealthily hijack up to 11.7× more (i.e., 23.5%) and 8.1× (i.e., 16.2%) more of the Internet (respectively) without being observed by the existing public route collector infrastructure. Having evaluated the effectiveness of the existing public route collector infrastructure with current Internet datasets, we evaluated the effectiveness in realistic future scenarios of (i) more interconnected (flatter) Internet topologies as well as (ii) topologies where more network volunteers disclose their routes to the public collectors. Unfortunately, both types of hijackers are more effective in flatter Internet topologies. Omniscient hijackers could stealthily hijack up to 24.5× (i.e., 49.0%) more of the Internet while realistic hijackers up to 22.7× (i.e., 45.5%) more without being observed by route collectors. In topologies with up to 4× more volunteers disclosing their routes to the public route collectors, hijackers could react to these new monitors by modifying their attacks to stealthily hijack up to 4× (i.e., 8.2%) and 2.9× (i.e., 5.9%) more of the Internet (respectively). Finally, we conclude with an analysis of two suggestions for improving the existing public route collector infrastructure: (i) selecting new network volunteers in more strategic locations and (ii) having volunteers disclose more routes to the route collectors. We hope that our findings in simulations will help towards the design of more reliable public route monitoring infrastructures. / Ruttkapningar har plågat internet i årtionden. Dessa attacker korrumperar poster i routingtabeller som används av nätverket för att vidarebefordra trafik, på ett sådant sätt att påverkade enheter dirigerar privat och tänkbart känslig trafik till kaparen. Trots många misslyckade försök att hindra kapare, ger på senare tid internetbred ruttövervakningsinfrastruktur oss förhoppningen att framtida system snabbt och slutgiltigt kan förhindra kapningar. Sådan övervakningsinfrastruktur består av flera globalt distribuerade övervakningsenheter kallade ruttinsamlare. Nätverksvolontärer uppger sina rutter till sådana publika ruttinsamlare så att hela nätverket kan övervaka validiteten och stabiliteten av den utbytta ruttinformationen. Dessvärre kan kapare utnyttja denna information för att undvika att bli rapporterade till ruttinsamlare. I denna avhandling utvärderar vi effektiviteten av sådan övervakningsinfrastruktur mot två typer av kapnings scenarier: Det första innefattar en allvetande attackerare med fullständig vetskap om både internettopologin och ruttpreferenser i nätverken. Det andra innefattar en realistisk attackerare som saknar sådan kunskap men som samlar upp den ruttinformation som nätverken själva lämnar ut till publika ruttinsamlare. Tidigare simuleringar har visat att kapningar som påverkar mer än 2% av internet alltid är synliga för den publika ruttinsamlarinfrastrukturen. Vår simulering visar däremot att allvetande och realistiska kapare som reagerar på utplaceringen av publika ruttinsamlare i smyg kan kapa upp till 11.7 gånger (d.v.s. 23.5%) respektive 8.1 gånger (d.v.s. 16.2%) mer av internet, utan att upptäckas av den existerande publika ruttinsamlarinfrastrukturen. Efter att ha utvärderat effektiviteten i den existerande publika infrastrukturen med nuvarande internet datamängder, utvärderade vi effektiviteten i realistiska framtida scenarier av för det första fler sammanlänkad (plattare) internet topologier samt för det andra topologier där fler nätverksvolontärer uppger sina rutter till publika ruttinsamlare. Dessvärre är båda typer av kapare mer effektiva i plattare internet topologier. Allvetande kapare kunde i smyg kapa upp till 24.5 gånger (d.v.s. 49.0%) mer av internet, medan realistiska kapare kunde kapa upp till 22.7 gånger (d.v.s. 45.5%) mer av internet, utan att upptäckas av ruttinsamlare. I topologier med upp till 4 gånger fler nätverksvolontärer som uppger sina rutter till publika ruttinsamlare, kunde allvetande och realistiska kapare reagerar på nya övervakare genom att modifiera sina attacker till att i smyg kapa upp till 4 gånger (d.v.s. 8.2%) respektive 2.9 gånger (d.v.s. 5.9%) mer av internet. Slutligen sammanfattar vi med en analys av två förslag till förbättring av den existerande ruttinsamlarinfrastrukturen: I det första väljes nya nätverksvolontärer på mer strategiska platser och i det andra låter vi nätverksvolontärer uppge fler rutter till ruttinsamlare. Vi hoppas att våra simuleringsresultat kan bidra till en design av en mer pålitlig publik rutt övervakningsinfrastruktur. / <p>QC 20220524</p>

[pt] Esta pesquisa-intervenção teve como objetivo compreender como os agentes e as artesãs do Museu de Favela conceberam a conceituação e a criação em parceria de suvenires do Circuito Casas-Tela por intermédio da ativação de um procedimento para registrar os signos das favelas do Cantagalo, Pavão-Pavãozinho com a equipe do NIMESC/PUC-Rio. Partindo do diálogo de autores que se afiliam a uma perspectiva teórica da semiologia translinguística, da filosofia crítica da cultura e da sociologia crítica, foi realizado um trabalho de design participativo com os agentes do Museu de Favela. Os dados foram coletados em uma pesquisa de campo nessas comunidades por intermédio de oficinas de conceituação e de criação com os agentes do Museu e as artesãs. Os dados revelaram que a participação da atuação do designer em uma comunidade necessita de uma parceria científica próxima, que observa os dispositivos que captam os processos que se singularizam, fazendo-os parte integrante da formulação de uma identidade local potente, expressa na linguagem dos suvenires com as técnicas artesanais. / [en] This intervention research aimed at understanding how agents and the craftspeople of the Favela Museum designed the conception and creation in partnership of souvenirs of Circuit of Houses-Art (Casas-Tela) through the activation of a procedure to record the signs of favelas of Cantagalo, Pavão- Pavãozinho, in Rio de Janeiro, with the team of NIMESC/PUC-Rio. From the authors dialog that are affiliated with a theoretical perspective of translinguistic semiotic, from critical philosophy of culture and critical sociology, a participatory design work has been performed with the agents of Favela Museum. Data have collected in field research in these communities through conceptualization and creation workshops with agents of the Museum and craftspeople. Data revealed that the participation of the designer s role in a community requires a close scientific partnership, which observes the devices that capture the processes that are significant. They make themselves an integral part of the formulation of a powerful local identity, expressed in the language of souvenirs with handcrafted techniques.

By investigating digital maps with an inclusive- and research through design approach, this research project aims on answering the research question: how can a digital map convey accessibility information of a route before the journey without the need of special adaptation?The research question involves two issues, how digital maps can convey information about a route and what accessibility information of a route is.With Rätt från början and the Swedish Agency for Accessible Media as stakeholders, a recruitment of participants with different capabilities, preference, characteristics, and needs was completed to explore how the participants use digital maps and perceive accessibility of the physical world by using the methods of interviews and design probes.The design process resulted in prototypes of a digital map that affords exploration without displaying normative standards of accessibility by using a design strategy of presenting the world as it is through audio-haptic and visual communication.

When it comes to dry powder inhalation (DPI), adhesive mixtures are the most widely used formulation type. Various techniques have been developed to generate inhaled drug particles and improve the delivery efficiency of DPI formulations. For dry powder inhaler formulations (DPIs), micronized drug powders are usually mixed with lactose carriers to improve powder handling during manufacturing and powder aerosol delivery during patient use. The performance of DPI systems is strongly dependent on several formulation factors, the construction of the delivery device and the inhalation technique. There is a growing interest in DPI in new medical areas such as vaccines and antibiotics which requires further development and challenges to ensure physical and aerosolization stability of DPI.  This project aims to discuss the development of inhalation therapy, the challenges during formulation processes, the mixing process and the use of excipients in pulmonary drug delivery in DPIs. Further, the project is covered by experiments based on the literature overview and performed at the Department of Pharmaceutical Biosciences at Uppsala University. Bulk density was measured on three series of adhesive mixtures with increasing amounts of fine particles. In two series, small amounts of Magnesium Stearate, 0,1% and 0,01% were added.

Die molekularen Tantal-Komplexe [TaCl4(NMe2)(OEt2)], [TaCl4(NEt2)(OEt2)], [TaCl3(NEt2)(OiPr)]2, [TaCl4(NEt2)]2, [TaCl3(NEt2)2]2, sowie die Pentachloroetherate [MCl5(OEt2)] (M=Nb, Ta) wurden synthetisiert und ihre Kristallstruktur aufgeklärt. Bei der Zersetzung der Chloridetherate in die korrespondierenden Oxidtrichloride, konnte die vermutete Abspaltung von Ethylchlorid bestätigt werden. Bei den Untersuchungen zur Leistungsfähigkeit der Polyol-Route wurden binäre und ternäre Sulfide, welche sich nicht im wäßrigen System fällen lassen, synthetisiert. Die Sulfide der Gruppe 10 konnten erstmals unter den milden Reaktionsbedingungen der Polyol-Route erhalten werden. Im Falle der untersuchten ternären Cuprosulfide von Indium, Zinn und Antimon, konnte gezeigt werden, daß diese durch die Präparation mittels Polyol-Route zunächst kubisch mit ungeordnetem Kationenteilgitter kristallisieren. Durch eine anschließende thermische Behandlung bei 623 K wurden diese in die tetragonal geordneten Modifikationen überführt. Bei der polyol-vermittelten Synthese binärer und ternärer Selenide wurde erstmals Selenoharnstoff erfolgreich eingesetzt. Hiermit konnte im Zuge der Synthese eine homogene, molekulare Lösung erhalten werden, bei der eine optimale Durchmischung der anionischen und kationischen Edukte gewährleistet ist. Das ternäre Mischoxid LaTaO4 wurde erfolgreich mit Hilfe der Polyol-Route hergestellt und in einem Wirbelschichtreaktor zu La2Ta2O5N2 umgesetzt. Dafür wurde eine neue Anlage entwickelt. Es konnte gezeigt werden, daß die Präparation von Tantaloxidnitriden im Wirbelschichtreaktor mit einem geringeren Ammoniak-Verbrauch als bei der bisherigen Prozeßführung möglich ist.

In this study, a new SUE model using the Weibull random error terms is proposed as an alternative to overcome the drawbacks of the multinomial logit (MNL) SUE model. A path-size weibit (PSW) model is developed to relax both independently and identically distributed assumptions, while retaining an analytical closed-form solution. Specifically, this route choice model handles route overlapping through the path-size factor and captures the route-specific perception variance through the Weibull distributed random error terms. Both constrained entropy-type and unconstrained equivalent MP formulations for the PSW-SUE are provided. In addition, model extensions to consider the demand elasticity and combined travel choice of the PSW-SUE model are also provided. Unlike the logit-based model, these model extensions incorporate the logarithmic expected perceived travel cost as the network level of service to determine the demand elasticity and travel choice. Qualitative properties of these minimization programs are given to establish equivalency and uniqueness conditions. Both path-based and link-based algorithms are developed for solving the proposed MP formulations. Numerical examples show that the proposed models can produce a compatible traffic flow pattern compared to the multinomial probit (MNP) SUE model, and these models can be implemented in a real-world transportation network.

This master's thesis deals with design and implementation of program unit Access System for BUT Information System Apollo. The goal of this work is to analyze Oracle technology and chosen database schemes of access system. After that use results of analysis to design and to implement of application which provide functionality to creating access to the identification cards readers and support inspection of passing through identification cards readers. Project is creating in Borland Delphi 7.