932 resultados para Delivery system
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Content Centric Network (CCN) is a proposed future internet architecture that is based on the concept of contents name instead of the hosts name followed in the traditional internet architecture. CCN architecture might do changes in the existing internet architecture or might replace it completely. In this paper, we present modifications to the existing Domain Name System (DNS) based on the CCN architecture requirements without changing the existing routing architecture. Hence the proposed solution achieves the benefits of both CCN and existing network infrastructure (i.e. content based routing, independent of host location, caching and content delivery protocols).
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Emerging cybersecurity vulnerabilities in supervisory control and data acquisition (SCADA) systems are becoming urgent engineering issues for modern substations. This paper proposes a novel intrusion detection system (IDS) tailored for cybersecurity of IEC 61850 based substations. The proposed IDS integrates physical knowledge, protocol specifications and logical behaviours to provide a comprehensive and effective solution that is able to mitigate various cyberattacks. The proposed approach comprises access control detection, protocol whitelisting, model-based detection, and multi-parameter based detection. This SCADA-specific IDS is implemented and validated using a comprehensive and realistic cyber-physical test-bed and data from a real 500kV smart substation.
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Pulsatile, or “on-demand”, delivery systems have the capability to deliver a therapeutic molecule at the right time/site of action and in the right amount (1). Pulsatile delivery systems present multiple benefits over conventional dosage forms and provide higher patient compliance. The combination of stimuli-responsive materials with the drug delivery capabilities of hydrogel-forming MN arrays (2) opens an interesting area of research. In the present work we describe, a stimuli-responsive hydrogel-forming microneedle (MN) array that enable delivery of a clinically-relevant model drug (ibuprofen) upon application of UV radiation (Figure 1A). MN arrays were prepared using a micromolding technique using a polymer prepared from 2-hydroxyethyl methacrylate (HEMA) and ethylene glycol dimethacrylate (EGDMA) (Figure 1B). The arrays were loaded with up to 5% (w/w) ibuprofen included in a light-responsible conjugate (3,5-dimethoxybenzoin conjugate) (2). The presence of the conjugate inside the MN arrays was confirmed by Raman spectroscopy measurements. MN arrays were tested in vitro showing that they were able to deliver up to three doses of 50 mg of ibuprofen after application of an optical trigger (wavelength of 365 nm) over a long period of time (up to 160 hours) (Figure 1C and 1D). The work presented here is a probe of concept and a modified version of the system should be used as UV radiation is shown to be the major etiologic agent in the development of skin cancers. Consequently, for future applications of this technology an alternative design should be developed. Based on the previous research dealing with hydrogel forming MN arrays a suitable strategy will be to use hydrogel-forming MN arrays containing a backing layer made with the material described in this work as the drug reservoir (2). Finally, a porous layer of a material that blocks UV radiation should be included between the MN array and the drug reservoir. Therefore radiation can be applied to the system without reaching the skin surface. Therefore after modification, the system described here interesting properties as “on-demand” release system for prolonged periods of time. This technology has potential for use in “on-demand” delivery of a wide range of drugs in a variety of applications relevant to enhanced patient care.
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Thesis (Master's)--University of Washington, 2016-08
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Conventional wisdom in many agricultural systems across the world is that farmers cannot, will not, or should not pay the full costs associated with surface water delivery. Across Organisation for Economic Co-operation and Development (OECD) countries, only a handful can claim complete recovery of operation, maintenance, and capital costs; across Central and South Asia, fees are lower still, with farmers in Nepal, India, and Kazakhstan paying fractions of a U.S. penny for a cubic meter of water. In Pakistan, fees amount to roughly USD 1-2 per acre per season. However, farmers in Pakistan spend orders of magnitude more for diesel fuel to pump groundwater each season, suggesting a latent willingness to spend for water that, under the right conditions, could potentially be directed toward water-use fees for surface water supply. Although overall performance could be expected to improve with greater cost recovery, asymmetric access to water in canal irrigation systems leaves the question open as to whether those benefits would be equitably shared among all farmers in the system. We develop an agent-based model (ABM) of a small irrigation command to examine efficiency and equity outcomes across a range of different cost structures for the maintenance of the system, levels of market development, and assessed water charges. We find that, robust to a range of different cost and structural conditions, increased water charges lead to gains in both efficiency and concomitant improvements in equity as investments in canal infrastructure and system maintenance improve the conveyance of water resources further down watercourses. This suggests that, under conditions in which (1) farmers are currently spending money to pump groundwater to compensate for a failing surface water system, and (2) there is the possibility that through initial investment to provide perceptibly better water supply, genuine win-win solutions can be attained through higher water-use fees to beneficiary farmers.
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Thesis (Ph.D.)--University of Washington, 2016-08
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eingereicht von Alexandra Partenhauser
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BACKGROUND: Inactivating genes in vivo is an important technique for establishing their function in the adult nervous system. Unfortunately, conventional knockout mice may suffer from several limitations including embryonic or perinatal lethality and the compensatory regulation of other genes. One approach to producing conditional activation or inactivation of genes involves the use of Cre recombinase to remove loxP-flanked segments of DNA. We have studied the effects of delivering Cre to the hippocampus and neocortex of adult mice by injecting replication-deficient adeno-associated virus (AAV) and lentiviral (LV) vectors into discrete regions of the forebrain. RESULTS: Recombinant AAV-Cre, AAV-GFP (green fluorescent protein) and LV-Cre-EGFP (enhanced GFP) were made with the transgene controlled by the cytomegalovirus promoter. Infecting 293T cells in vitro with AAV-Cre and LV-Cre-EGFP resulted in transduction of most cells as shown by GFP fluorescence and Cre immunoreactivity. Injections of submicrolitre quantities of LV-Cre-EGFP and mixtures of AAV-Cre with AAV-GFP into the neocortex and hippocampus of adult Rosa26 reporter mice resulted in strong Cre and GFP expression in the dentate gyrus and moderate to strong labelling in specific regions of the hippocampus and in the neocortex, mainly in neurons. The pattern of expression of Cre and GFP obtained with AAV and LV vectors was very similar. X-gal staining showed that Cre-mediated recombination had occurred in neurons in the same regions of the brain, starting at 3 days post-injection. No obvious toxic effects of Cre expression were detected even after four weeks post-injection. CONCLUSION: AAV and LV vectors are capable of delivering Cre to neurons in discrete regions of the adult mouse brain and producing recombination
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Alginate microgels are widely used as delivery systems in food, cosmetics, and pharmaceutical industries for encapsulation and sustained release of hydrophilic compounds and cells. However, the encapsulation of lipophilic molecules inside these microgels remains a great challenge because of the complex oil-core matrix required. The present study describes an original two-step approach allowing the easy encapsulation of several oil microdroplets within alginate microgels. In the first step, stable oil microdroplets were formed by preparing an oil-in-water (O/W) Pickering emulsion. To stabilize this emulsion, we used two solid particles, namely the cotton cellulose nanocrystals (CNC) and calcium carbonate (CaCO3). It was observed that the surface of the oil microdroplets formed was totally covered by a CNC layer, whereas CaCO3 particles were adsorbed onto the cellulose layer. This solid CNC shell efficiently stabilized the oil microdroplets, preventing them from undesired coalescence. In the second step, oil microdroplets resulting from the Pickering emulsion were encapsulated within alginate microgels using microfluidics. Precisely, the outermost layer of oil microdroplets composed of CaCO3 particles was used to initiate alginate gelation inside the microfluidic device, following the internal gelation mode. The released Ca2+ ions induced the gel formation through physical cross-linking with alginate molecules. This innovative and easy to carry out two-step approach was successfully developed to fabricate monodisperse alginate microgels of 85 pm in diameter containing around 12 oil microdroplets of 15 mu m in diameter. These new oil-core alginate microgels represent an attractive system for encapsulation of lipophilic compounds such as vitamins, aroma compounds or anticancer drugs that could be applied in various domains including food, cosmetics, and medical applications.
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In many major cities, fixed route transit systems such as bus and rail serve millions of trips per day. These systems have people collect at common locations (the station or stop), and board at common times (for example according to a predetermined schedule or headway). By using common service locations and times, these modes can consolidate many trips that have similar origins and destinations or overlapping routes. However, the routes are not sensitive to changing travel patterns, and have no way of identifying which trips are going unserved, or are poorly served, by the existing routes. On the opposite end of the spectrum, personal modes of transportation, such as a private vehicle or taxi, offer service to and from the exact origin and destination of a rider, at close to exactly the time they desire to travel. Despite the apparent increased convenience to users, the presence of a large number of small vehicles results in a disorganized, and potentially congested road network during high demand periods. The focus of the research presented in this paper is to develop a system that possesses both the on-demand nature of a personal mode, with the efficiency of shared modes. In this system, users submit their request for travel, but are asked to make small compromises in their origin and destination location by walking to a nearby meeting point, as well as slightly modifying their time of travel, in order to accommodate other passengers. Because the origin and destination location of the request can be adjusted, this is a more general case of the Dial-a-Ride problem with time windows. The solution methodology uses a graph clustering algorithm coupled with a greedy insertion technique. A case study is presented using actual requests for taxi trips in Washington DC, and shows a significant decrease in the number of vehicles required to serve the demand.
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The first goal of this study is to analyse a real-world multiproduct onshore pipeline system in order to verify its hydraulic configuration and operational feasibility by constructing a simulation model step by step from its elementary building blocks that permits to copy the operation of the real system as precisely as possible. The second goal is to develop this simulation model into a user-friendly tool that one could use to find an “optimal” or “best” product batch schedule for a one year time period. Such a batch schedule could change dynamically as perturbations occur during operation that influence the behaviour of the entire system. The result of the simulation, the ‘best’ batch schedule is the one that minimizes the operational costs in the system. The costs involved in the simulation are inventory costs, interface costs, pumping costs, and penalty costs assigned to any unforeseen situations. The key factor to determine the performance of the simulation model is the way time is represented. In our model an event based discrete time representation is selected as most appropriate for our purposes. This means that the time horizon is divided into intervals of unequal lengths based on events that change the state of the system. These events are the arrival/departure of the tanker ships, the openings and closures of loading/unloading valves of storage tanks at both terminals, and the arrivals/departures of trains/trucks at the Delivery Terminal. In the feasibility study we analyse the system’s operational performance with different Head Terminal storage capacity configurations. For these alternative configurations we evaluated the effect of different tanker ship delay magnitudes on the number of critical events and product interfaces generated, on the duration of pipeline stoppages, the satisfaction of the product demand and on the operative costs. Based on the results and the bottlenecks identified, we propose modifications in the original setup.
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Efficient and reliable techniques for power delivery and utilization are needed to account for the increased penetration of renewable energy sources in electric power systems. Such methods are also required for current and future demands of plug-in electric vehicles and high-power electronic loads. Distributed control and optimal power network architectures will lead to viable solutions to the energy management issue with high level of reliability and security. This dissertation is aimed at developing and verifying new techniques for distributed control by deploying DC microgrids, involving distributed renewable generation and energy storage, through the operating AC power system. To achieve the findings of this dissertation, an energy system architecture was developed involving AC and DC networks, both with distributed generations and demands. The various components of the DC microgrid were designed and built including DC-DC converters, voltage source inverters (VSI) and AC-DC rectifiers featuring novel designs developed by the candidate. New control techniques were developed and implemented to maximize the operating range of the power conditioning units used for integrating renewable energy into the DC bus. The control and operation of the DC microgrids in the hybrid AC/DC system involve intelligent energy management. Real-time energy management algorithms were developed and experimentally verified. These algorithms are based on intelligent decision-making elements along with an optimization process. This was aimed at enhancing the overall performance of the power system and mitigating the effect of heavy non-linear loads with variable intensity and duration. The developed algorithms were also used for managing the charging/discharging process of plug-in electric vehicle emulators. The protection of the proposed hybrid AC/DC power system was studied. Fault analysis and protection scheme and coordination, in addition to ideas on how to retrofit currently available protection concepts and devices for AC systems in a DC network, were presented. A study was also conducted on the effect of changing the distribution architecture and distributing the storage assets on the various zones of the network on the system’s dynamic security and stability. A practical shipboard power system was studied as an example of a hybrid AC/DC power system involving pulsed loads. Generally, the proposed hybrid AC/DC power system, besides most of the ideas, controls and algorithms presented in this dissertation, were experimentally verified at the Smart Grid Testbed, Energy Systems Research Laboratory. All the developments in this dissertation were experimentally verified at the Smart Grid Testbed.
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Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering (HVTE) owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by steady flow and scaffold flexure play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). In addition, scaffold flexure may enhance nutrient (e.g. oxygen, glucose) transport. In this study, we computationally quantified the i) magnitude of fluid-induced shear stresses; ii) the extent of temporal fluid oscillations in the flow field using the oscillatory shear index (OSI) parameter, and iii) glucose and oxygen mass transport profiles. Noting that sample cyclic flexure induces a high degree of oscillatory shear stress (OSS), we incorporated moving boundary computational fluid dynamic simulations of samples housed within a bioreactor to consider the effects of: 1) no flow, no flexure (control group), 2) steady flow-alone, 3) cyclic flexure-alone and 4) combined steady flow and cyclic flexure environments. We also coupled a diffusion and convention mass transport equation to the simulated system. We found that the coexistence of both OSS and appreciable shear stress magnitudes, described by the newly introduced parameter OSI-:τ: explained the high levels of engineered collagen previously observed from combining cyclic flexure and steady flow states. On the other hand, each of these metrics on its own showed no association. This finding suggests that cyclic flexure and steady flow synergistically promote engineered heart valve tissue production via OSS, so long as the oscillations are accompanied by a critical magnitude of shear stress. In addition, our simulations showed that mass transport of glucose and oxygen is enhanced by sample movement at low sample porosities, but did not play a role in highly porous scaffolds. Preliminary in-house in vitro experiments showed that cell proliferation and phenotype is enhanced in OSI-:τ: environments.^
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Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.
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Cassava contributes significantly to biobased material development. Conventional approaches for its bio-derivative-production and application cause significant wastes, tailored material development challenges, with negative environmental impact and application limitations. Transforming cassava into sustainable value-added resources requires redesigning new approaches. Harnessing unexplored material source, and downstream process innovations can mitigate challenges. The ultimate goal proposed an integrated sustainable process system for cassava biomaterial development and potential application. An improved simultaneous release recovery cyanogenesis (SRRC) methodology, incorporating intact bitter cassava, was developed and standardized. Films were formulated, characterised, their mass transport behaviour, simulating real-distribution-chain conditions quantified, and optimised for desirable properties. Integrated process design system, for sustainable waste-elimination and biomaterial development, was developed. Films and bioderivatives for desired MAP, fast-delivery nutraceutical excipients and antifungal active coating applications were demonstrated. SRRC-processed intact bitter cassava produced significantly higher yield safe bio-derivatives than peeled, guaranteeing 16% waste-elimination. Process standardization transformed entire root into higher yield and clarified colour bio-derivatives and efficient material balance at optimal global desirability. Solvent mass through temperature-humidity-stressed films induced structural changes, and influenced water vapour and oxygen permeability. Sevenunit integrated-process design led to cost-effectiveness, energy-efficient and green cassava processing and biomaterials with zero-environment footprints. Desirable optimised bio-derivatives and films demonstrated application in desirable in-package O2/CO2, mouldgrowth inhibition, faster tablet excipient nutraceutical dissolutions and releases, and thymolencapsulated smooth antifungal coatings. Novel material resources, non-root peeling, zero-waste-elimination, and desirable standardised methodology present promising process integration tools for sustainable cassava biobased system development. Emerging design outcomes have potential applications to mitigate cyanide challenges and provide bio-derivative development pathways. Process system leads to zero-waste, with potential to reshape current style one-way processes into circular designs modelled on nature's effective approaches. Indigenous cassava components as natural material reinforcements, and SRRC processing approach has initiated a process with potential wider deployment in broad product research development. This research contributes to scientific knowledge in material science and engineering process design.