Physical and financial follow-up of investment projects: a methodology for the Project Information System

Includes bibliography

Consuming viscous prey: a novel protein-secreting delivery system in neotropical snail-eating snakes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Development and characterization of biocompatible isotropic and anisotropic oil-in-water colloidal dispersions as a new delivery system for methyl dihydrojasmonate antitumor drug

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Use of E. coli OMVs as delivery system to elicit neutralizing antibodies against Chlamydia infectivity: the HtrA protein example

The obligate intracellular pathogen Chlamydia trachomatis is a gram negative bacterium which infects epithelial cells of the reproductive tract. C. trachomatis is the leading cause of bacterial sexually transmitted disease worldwide and a vaccine against this pathogen is highly needed. Many evidences suggest that both antigen specific-Th1 cells and antibodies may be important to provide protection against Chlamydia infection. In a previous study we have identified eight new Chlamydia antigens inducing CD4-Th1 and/or antibody responses that, when combined properly, can protect mice from Chlamydia infection. However, all selected recombinant antigens, upon immunization in mice, elicited antibodies not able to neutralize Chlamydia infectivity in vitro. With the aim to improve the quality of the immune response by inducing effective neutralizing antibodies, we used a novel delivery system based on the unique capacity of E. coli Outer Membrane Vesicles (OMV) to present membrane proteins in their natural composition and conformation. We have expressed Chlamydia antigens, previously identified as vaccine candidates, in the OMV system. Among all OMV preparations, the one expressing HtrA Chlamydia antigen (OMV-HtrA), showed to be the best in terms of yield and quantity of expressed protein, was used to produce mice immune sera to be tested in neutralization assay in vitro. We observed that OMV-HtrA elicited specific antibodies able to neutralize efficiently Chlamydia infection in vitro, indicating that the presentation of the antigens in their natural conformation is crucial to induce an effective immune response. This is one of the first examples in which antibodies directed against a new Chlamydia antigen, other than MOMP (the only so far known antigen inducing neutralizing antibodies), are able to block the Chlamydia infectivity in vitro. Finally, by performing an epitope mapping study, we investigated the specificity of the antibody response induced by the recombinant HtrA and by OMV-HtrA. In particular, we identified some linear epitopes exclusively recognized by antibodies raised with the OMV-HtrA system, detecting in this manner the antigen regions likely responsible of the neutralizing effect.

Multidimensional project control system: applicazione di verifica della qualità dei progetti in Despar Italia c.r.l.

La dissertazione affronterà il tema del controllo qualità nei progetti, applicando conoscenze, tecniche e strumenti propri del Project e del Multiproject Management. L’analisi partirà svolgendo, nel primo capitolo, considerazioni introduttive riguardo le due discipline citate. Lo scopo ultimo sarà quello di elaborare un sistema di controllo integrato della qualità, indirizzato principalmente al Project Management che è presente in una qualsiasi organizzazione che opera per progetti. Nel secondo capitolo verrà illustrato il metodo denominato Multidimensional Project control System sul quale il modello sviluppato in seguito si basa. La progettazione di un sistema di controllo è una parte importante dello sforzo di gestione di un progetto. Tale sistema è basato su una serie di obiettivi di progetto e sulla loro importanza relativa e fonda la sua natura su una sistematica valutazione in corso d’opera dello stato di conformità del progetto, sia a livello di processo che a livello di output. Nel capitolo conclusivo si affronta l’obiettivo principale di questo elaborato. Sono stati forniti dati e documenti dall’azienda Despar Italia c.r.l. ed è stato chiesto di sviluppare un metodo di controllo che il Project Management potesse utilizzare per implementare un processo di verifica della qualità di progetto. Viene quindi descritta l’azienda, come il Management pianifica, gestisce e controlla i progetti e quali necessità devono essere soddisfatte. Si procede poi con l’illustrazione e spiegazione del metodo sviluppato, chiarito da un esempio esplicativo. L’elaborato si concluderà con delle riflessioni finali, proponendo critiche e spunti per eventuali sviluppi futuri.

Synthesis of 1,1'-(Hexane-1,6-Diyl)Bis(5-Oxopyrrolidine-3-Carboxylic Acid) as a Monomer for a Polyanhydride Drug Delivery System

Polyanhydrides have been given much attention in the literature recently because of their desirable properties as controlled drug delivery solutions. Drug therapies could be loaded into a polyanhydride matrix and protected from denaturation and removal from the body while being slowly eluted as the polyanhydride degraded yielding a tailorable concentration profile in the bloodstream at therapeutic levels. To that end, this report discusses the synthesis of a novel monomer for polyanhydride synthesis: 1,1'-(hexane-1,6-diyl)bis(5-oxopyrrolidine-3-carboxylic acid) henceforth known as CPyH monomer for (carboxypyrrolidone)hexane monomer.

Antimicrobial therapy using a local drug delivery system (Arestin) in the treatment of peri-implantitis. I: Microbiological outcomes

OBJECTIVES: To assess the microbiological outcome of local administration of minocycline hydrochloride microspheres 1 mg (Arestin) in cases with peri-implantitis and with a follow-up period of 12 months. MATERIAL AND METHODS: After debridement, and local administration of chlorhexidine gel, peri-implantitis cases were treated with local administration of minocycline microspheres (Arestin). The DNA-DNA checkerboard hybridization method was used to detect bacterial presence during the first 360 days of therapy. RESULTS: At Day 10, lower bacterial loads for 6/40 individual bacteria including Actinomyces gerensceriae (P<0.1), Actinomyces israelii (P<0.01), Actinomyces naeslundi type 1 (P<0.01) and type 2 (P<0.03), Actinomyces odontolyticus (P<0.01), Porphyromonas gingivalis (P<0.01) and Treponema socranskii (P<0.01) were found. At Day 360 only the levels of Actinobacillus actinomycetemcomitans were lower than at baseline (mean difference: 1x10(5); SE difference: 0.34x10(5), 95% CI: 0.2x10(5) to 1.2x10(5); P<0.03). Six implants were lost between Days 90 and 270. The microbiota was successfully controlled in 48%, and with definitive failures (implant loss and major increase in bacterial levels) in 32% of subjects. CONCLUSIONS: At study endpoint, the impact of Arestin on A. actinomycetemcomitans was greater than the impact on other pathogens. Up to Day 180 reductions in levels of Tannerella forsythia, P. gingivalis, and Treponema denticola were also found. Failures in treatment could not be associated with the presence of specific pathogens or by the total bacterial load at baseline. Statistical power analysis suggested that a case control study would require approximately 200 subjects.

Antitumor activity of an epithelial cell adhesion molecule targeted nanovesicular drug delivery system

Site-specific delivery of anticancer agents to tumors represents a promising therapeutic strategy because it increases efficacy and reduces toxicity to normal tissues compared with untargeted drugs. Sterically stabilized immunoliposomes (SIL), guided by antibodies that specifically bind to well internalizing antigens on the tumor cell surface, are effective nanoscale delivery systems capable of accumulating large quantities of anticancer agents at the tumor site. The epithelial cell adhesion molecule (EpCAM) holds major promise as a target for antibody-based cancer therapy due to its abundant expression in many solid tumors and its limited distribution in normal tissues. We generated EpCAM-directed immunoliposomes by covalently coupling the humanized single-chain Fv antibody fragment 4D5MOCB to the surface of sterically stabilized liposomes loaded with the anticancer agent doxorubicin. In vitro, the doxorubicin-loaded immunoliposomes (SIL-Dox) showed efficient cell binding and internalization and were significantly more cytotoxic against EpCAM-positive tumor cells than nontargeted liposomes (SL-Dox). In athymic mice bearing established human tumor xenografts, pharmacokinetic and biodistribution analysis of SIL-Dox revealed long circulation times in the blood with a half-life of 11 h and effective time-dependent tumor localization, resulting in up to 15% injected dose per gram tissue. These favorable pharmacokinetic properties translated into potent antitumor activity, which resulted in significant growth inhibition (compared with control mice), and was more pronounced than that of doxorubicin alone and nontargeted SL-Dox at low, nontoxic doses. Our data show the promise of EpCAM-directed nanovesicular drug delivery for targeted therapy of solid tumors.

Content Delivery System for Optimal VoD Streaming

The demand of video contents has rapidly increased in the past years as a result of the wide deployment of IPTV and the variety of services offered by the network operators. One of the services that has especially become attractive to the customers is real-time video on demand (VoD) because it offers an immediate streaming of a large variety of video contents. The price that the operators have to pay for this convenience is the increased traffic in the networks, which are becoming more congested due to the higher demand for VoD contents and the increased quality of the videos. As a solution, in this paper we propose a hierarchical network system for VoD content delivery in managed networks, which implements redistribution algorithm and a redirection strategy for optimal content distribution within the network core and optimal streaming to the clients. The system monitors the state of the network and the behavior of the users to estimate the demand for the content items and to take the right decision on the appropriate number of replicas and their best positions in the network. The system's objectives are to distribute replicas of the content items in the network in a way that the most demanded contents will have replicas closer to the clients so that it will optimize the network utilization and will improve the users' experience. It also balances the load between the servers concentrating the traffic to the edges of the network.

A hardware in the loop design methodology for FPGA system and its application to complex functions

In this work, a unified algorithm-architecture-circuit co-design environment for complex FPGA system development is presented. The main objective is to find an efficient methodology for designing a configurable optimized FPGA system by using as few efforts as possible in verification stage, so as to speed up the development period. A proposed high performance FFT/iFFT processor for Multiband Orthogonal Frequency Division Multiplexing Ultra Wideband (MB-OFDM UWB) system design process is given as an example to demonstrate the proposed methodology. This efficient design methodology is tested and considered to be suitable for almost all types of complex FPGA system designs and verifications.

THE DESIGN OF A POWER SYSTEM FOR A WIRELESS SENSOR NETWORK FOR LONG-TERM OPERATION

Wireless sensor networks (WSNs) have shown wide applicability to many fields including monitoring of environmental, civil, and industrial settings. WSNs however are resource constrained by many competing factors that span their hardware, software, and networking. One of the central resource constrains is the charge consumption of WSN nodes. With finite energy supplies, low charge consumption is needed to ensure long lifetimes and success of WSNs. This thesis details the design of a power system to support long-term operation of WSNs. The power system’s development occurs in parallel with a custom WSN from the Queen’s MEMS Lab (QML-WSN), with the goal of supporting a 1+ year lifetime without sacrificing functionality. The final power system design utilizes a TPS62740 DC-DC converter with AA alkaline batteries to efficiently supply the nodes while providing battery monitoring functionality and an expansion slot for future development. Testing tools for measuring current draw and charge consumption were created along with analysis and processing software. Through their use charge consumption of the power system was drastically lowered and issues in QML-WSN were identified and resolved including the proper shutdown of accelerometers, and incorrect microcontroller unit (MCU) power pin connection. Controlled current profiling revealed unexpected behaviour of nodes and detailed current-voltage relationships. These relationships were utilized with a lifetime projection model to estimate a lifetime between 521-551 days, depending on the mode of operation. The power system and QML-WSN were tested over a long term trial lasting 272+ days in an industrial testbed to monitor an air compressor pump. Environmental factors were found to influence the behaviour of nodes leading to increased charge consumption, while a node in an office setting was still operating at the conclusion of the trail. This agrees with the lifetime projection and gives a strong indication that a 1+ year lifetime is achievable. Additionally, a light-weight charge consumption model was developed which allows charge consumption information of nodes in a distributed WSN to be monitored. This model was tested in a laboratory setting demonstrating +95% accuracy for high packet reception rate WSNs across varying data rates, battery supply capacities, and runtimes up to full battery depletion.

Novel particulate BCG-loaded delivery system for mucosal immunization against tuberculosis

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2016