912 resultados para Design Build Project Delivery System
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Assessing frequency and extent of mass movement at continental margins is crucial to evaluate risks for offshore constructions and coastal areas. A multidisciplinary approach including geophysical, sedimentological, geotechnical, and geochemical methods was applied to investigate multistage mass transport deposits (MTDs) off Uruguay, on top of which no surficial hemipelagic drape was detected based on echosounder data. Nonsteady state pore water conditions are evidenced by a distinct gradient change in the sulfate (SO4**2-) profile at 2.8 m depth. A sharp sedimentological contact at 2.43 m coincides with an abrupt downward increase in shear strength from approx. 10 to >20 kPa. This boundary is interpreted as a paleosurface (and top of an older MTD) that has recently been covered by a sediment package during a younger landslide event. This youngest MTD supposedly originated from an upslope position and carried its initial pore water signature downward. The kink in the SO4**2- profile approx. 35 cm below the sedimentological and geotechnical contact indicates that bioirrigation affected the paleosurface before deposition of the youngest MTD. Based on modeling of the diffusive re-equilibration of SO4**2- the age of the most recent MTD is estimated to be <30 years. The mass movement was possibly related to an earthquake in 1988 (approx. 70 km southwest of the core location). Probabilistic slope stability back analysis of general landslide structures in the study area reveals that slope failure initiation requires additional ground accelerations. Therefore, we consider the earthquake as a reasonable trigger if additional weakening processes (e.g., erosion by previous retrogressive failure events or excess pore pressures) preconditioned the slope for failure. Our study reveals the necessity of multidisciplinary approaches to accurately recognize and date recent slope failures in complex settings such as the investigated area.
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Several previous studies have shown that submarine mass-movements can profoundly impact the shape of pore water profiles. Therefore, pore water geochemistry and diffusion models were proposed as tools for identifying and dating recent (max. several thousands of years old) mass-transport deposits (MTDs). In particular, sulfate profiles evidentially indicate transient pore water conditions generated by submarine landslides. After mass-movements that result in the deposition of sediment packages with distinct pore water signatures, the sulfate profiles can be kink-shaped and evolve into the concave and linear shape with time due to molecular diffusion. Here we present data from the RV METEOR cruise M78/3 along the continental margin off Uruguay and Argentina. Sulfate profiles of 15 gravity cores are compared with the respective acoustic facies recorded by a sediment echosounder system. Our results show that in this very dynamic depositional setting, non-steady state profiles occur often, but are not exclusively associated with mass-movements. Three sites that show acoustic indications for recent MTDs are presented in detail. Where recent MTDs are identified, a geochemical transport/reaction model is used to estimate the time that has elapsed since the perturbation of the pore water system and, thus, the timing of the MTD emplacement. We conclude that geochemical analyses are a powerful complementary tool in the identification of recent MTDs and provide a simple and accurate way of dating such deposits.
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Objectives: The current study aims to evaluate dosage form preferences in children and young adults together with identifying the key pragmatic dosage form characteristics that would enable appropriate formulation of orally disintegrating tablets (ODTs). Methods: International, multisite, cross-sectional questionnaire of children and young adults aged from 6 to 18 years. Eligibility was based on age, ability to communicate and previous experience in taking medications. The study was carried out at three locations: the UK, Saudi Arabia and Jordan. The questionnaire instrument was designed for participant self-completion under supervision of the study team.Results 104 questionnaires were completed by the study cohort (n=120, response rate 87%). Results: showed that ODTs were the most preferred oral dosage forms (58%) followed by liquids (20%), tablets (12%) and capsules (11%). The preferred colours were pink or white while the preferred size was small (<8 mm) with a round shape. With regard to flavour, strawberry was the most preferred (30.8%), while orange was the least preferred (5.8%). The results also showed that the most important physical characteristics of ODTs were disintegration time followed by taste, size and flavour, respectively. Conclusions: The results of our study support the WHO's claim for a shift of paradigm from liquid towards ODTs dosage forms for drug administration to young children older than 6 years. Data from this study will also equip formulators to prioritise development of key physical/performance attributes within the delivery system.
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Smart hydrogels for biomedical applications are highly researched materials. However, integrating them into a device for implantation is difficult. This paper investigates an integrated delivery device designed to deliver an electro-responsive hydrogel to a target location inside a blood vessel with the purpose of creating an occlusion. The paper describes the synthesis and characterization of a Pluronic/methacrylic acid sodium salt electro-responsive hydrogel. Application of an electrical bias decelerates the expansion of the hydrogel. An integrated delivery system was manufactured to deliver the hydrogel to the target location in the body. Ex vivo and in vivo experiments in the carotid artery of sheep were used to validate the concept. The hydrogel was able to completely occlude the blood vessel reducing the blood flow from 245 to 0 ml/min after implantation. Ex vivo experiments showed that the hydrogel was able to withstand physiological blood pressures of > 270 mm·Hg without dislodgement. The results showed that the electro-responsive hydrogel used in this paper can be used to create a long-term occlusion in a blood vessel without any apparent side effects. The delivery system developed is a promising device for the delivery of electro-responsive hydrogels.
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L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures.
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The neoliberal period was accompanied by a momentous transformation within the US health care system. As the result of a number of political and historical dynamics, the healthcare law signed by President Barack Obama in 2010 ‑the Affordable Care Act (ACA)‑ drew less on universal models from abroad than it did on earlier conservative healthcare reform proposals. This was in part the result of the influence of powerful corporate healthcare interests. While the ACA expands healthcare coverage, it does so incompletely and unevenly, with persistent uninsurance and disparities in access based on insurance status. Additionally, the law accommodates an overall shift towards a consumerist model of care characterized by high cost sharing at time of use. Finally, the law encourages the further consolidation of the healthcare sector, for instance into units named “Accountable Care Organizations” that closely resemble the health maintenance organizations favored by managed care advocates. The overall effect has been to maintain a fragmented system that is neither equitable nor efficient. A single payer universal system would, in contrast, help transform healthcare into a social right.
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This thesis explores how to design a peer support system to facilitate self-organized knowledge sharing in non-formal learning environments, in particular when learners work on complex tasks. The peer support system aims to replace two teacher-led didactic arrangements: selecting a tutor at the initial stage, and guidance during the interaction process (Dillenbourg, 1999; Topping, 1996). Such a system has previously been developed by Van Rosmalen (2008) and De Bakker (2010) and has been tentatively used to facilitate knowledge sharing on content-related questions. In this thesis, we would like to find out how to further improve the design of this peer support system, especially to facilitate knowledge sharing on complex tasks. Since little pedagogical theory is available to inform the design of our peer support system, this thesis attempts to apply cognitive load theory (Sweller, Van Merriënboer, & Paas, 1998; Van Merriënboer & Sweller, 2005) that informs instructional designs in classroom settings to the design of our peer support system in Learning Networks.
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Treatment of hepatocellular cancer with chemotherapeutic agents has limited successin clinical practice and their efficient IC50 concentration would require extremely highdoses of drug administration which could not be tolerated due to systemic side effects.In order to potentiate the efficacy of anticancer agents we explored the potentialof co-treatment with pro-apoptotic Cytochrome c which activates the apoptoticpathway downstream of p53 that is frequently mutated in cancer. To this end weused hybrid iron oxide-gold nanoparticles as a drug delivery system to facilitate theinternalisation of Cytochrome c into cultured HepG2 hepatocellular carcinoma cells.Our results showed that Cytochrome c can be easily conjugated to the gold shell ofthe nanoparticles which are readily taken up by the cells. We used Cytochrome cin concentration (0.2μgmL-1) below the threshold required to induce apoptosis onits own. When the conjugate was administered to cells treated by doxorubicin, itsignificantly reduced its IC50 concentration from 9μgmL-1 to 3.5μgmL-1 as detectedby cell viability assay, and the efficiency of doxorubicin on decreasing viability ofHepG2 cells was significantly enhanced in the lower concentration range between0.01μgmL-1 to 5μgmL-1. The results demonstrate the potential of the application oftherapeutic proteins in activating the apoptotic pathway to complement conventionalchemotherapy to increase its efficacy. The application of hybrid iron oxide-goldnanoparticles can also augment the specificity of drug targeting and could serve as amodel drug delivery system for pro-apoptotic protein targeting and delivery.
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To minimize the side effects and the multidrug resistance (MDR) arising from daunorubicin (DNR) treatment of malignant lymphoma, a chemotherapy formulation of cysteamine-modified cadmium tellurium (Cys-CdTe) quantum dots coloaded with DNR and gambogic acid (GA) nanoparticles (DNR-GA-Cys-CdTe NPs) was developed. The physical property, drug-loading efficiency and drug release behavior of these DNR-GA-Cys-CdTe NPs were evaluated, and their cytotoxicity was explored by 3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyltetrazolium bromide assay. These DNR-GA-Cys-CdTe NPs possessed a pH-responsive behavior, and displayed a dose-dependent antiproliferative activity on multidrug-resistant lymphoma Raji/DNR cells. The accumulation of DNR inside the cells, revealed by flow cytometry assay, and the down-regulated expression of P-glycoprotein inside the Raji/DNR cells measured by Western blotting assay indicated that these DNR-GA-Cys-CdTe NPs could minimize the MDR of Raji/DNR cells. This multidrug delivery system would be a promising strategy for minimizing MDR against the lymphoma.
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The aim of this report is to give an overview of the results of Work Package 5 “Engineering Tools”. In this workpackage numerical tools have been developed for all relevant CHCP systems in the PolySMART demonstration projects (WP3). First, existing simulation platforms have been described and specific characteristics have been identified. Several different simulation platforms are in principle appropriate for the needs in the PolySMART project. The result is an evaluation of available simulation and engineering tools for CHCP simulation, and an agreement upon a common simulation environment within the PolySMART project. Next, numerical models for components in the demonstration projects have been developed. These models are available to the PolySMART consortium. Of all modeled components an overall and detailed working principle is formulated, including a parameter list and (in some cases) a control strategy. Finally, for four CHCP systems in the PolySMART project, a system simulation model has been developed. For each system simulation a separate deliverable is available (D5.5b to D5.5e) These deliverables replace deliverable 5.4 ‘system models’. The numerical models for components and systems developed in the Polysmart project form a valuable basis for the component development and optimisation and for the system optimisation, both within and outside the project. Developers and researchers interested in more information about specific models can refer to the institutes and contact persons involved in the model development.
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Dissertacao (Mestrado)
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The Hive represents a completely new vision for libraries and, since opening in 2012, has helped us constantly review and change our approach to service delivery. Our most recent work is around student engagement, where we are changing our relationship with students moving from passive recipients of services to active participants in service design, evaluation and delivery. This presentation will cover some examples of our student engagement work, the benefits it brings and some of the challenges that we face.
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Thesis (Ph.D.)--University of Washington, 2016-07
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Thesis (Ph.D.)--University of Washington, 2016-08