<p>Cancer is currently the second leading cause of death in the United States. Although many treatment options exist, some of the most common, including radiotherapy and chemotherapy, are restricted by dose-limiting toxicities. In addition, the largest hurdle for translating novel biological therapies such as siRNA into the clinic is lack of an efficient delivery mechanism to get the therapeutic into malignant cells. This work aims to improve this situation by engineering a minimally invasive controlled release system that specifically delivers therapeutics to the site of malignant tissue. This platform consists of two novel material components: a thermally responsive poly[N-isopropylacrylamide-co-acrylamide] (NIPAAm-co-AAm) hydrogel and gold-silica nanoshells. Therapeutic molecules are encapsulated within a poly(NIPAAm-co-AAm) hydrogel carrier, leading to increased serum stability, circulation time, and decreased exposure to off-site tissues. Additionally, gold-silica nanoshells embedded within this hydrogel will be used to optically trigger therapeutic release from the carrier. This hydrogel-nanoshell composite material was designed to be swollen under physiologic conditions (37 oC), and expel large amounts of water and absorbed molecules at higher temperatures (40-45 oC). This phase transition can be optically triggered by embedded gold-silica nanoshells, which rapidly transfer near-infrared (NIR) light energy into heat due to the surface plasmon resonance phenomena. NIR light can deeply penetrate biological tissue with little attenuation or damage to tissue, and upon exposure to such light a rapid temperature increase, hydrogel collapse, and drug expulsion will occur. Ultimately, these drug-loaded hydrogel-nanoshell composite particles would be injected intravenously, passively accumulate in tumor tissue due to the enhanced permeability and retention (EPR) effect, and then can be externally triggered to release their therapeutic payload by exposure to an external NIR laser. This dissertation describes the synthesis, characterization, and validation of such a controlled therapeutic delivery platform.</p><p>Initial validation of poly(NIPAAm-co-AAm)-gold nanoshell composites to act as a material in site-specific cancer therapeutic delivery was accomplished using bulk hydrogel-nanoparticle composite disks. The composite material underwent a phase transition from a hydrated to a collapsed state following exposure to NIR light, indicating the ability of the NIR absorption by the nanoshells to sufficiently drive this transition. The composite material was loaded with either doxorubicin or a DNA duplex (a model nucleic acid therapeutic), two cancer therapeutics with differing physical and chemical properties. Release of both therapeutics was dramatically enhanced by NIR light exposure, causing 2-5 fold increase in drug release. Drug delivery profiles were influenced by both the molecular size of the drug as well as its chemical properties. </p><p>Towards translation of this material into in vivo applications, the hydrogel-nanoshell composite material was synthesized as injectable-sized particles. Such particles retained the same thermal properties as the bulk material, collapsing in size from ~330 nm to ~270 nm upon NIR exposure. Furthermore, these particles were loaded with the chemotherapeutic doxorubicin and NIR exposure triggered a burst release of the drug payload over only 3 min. In vitro, this platform provided increased delivery of doxorubicin to colon carcinoma cells compared to free-drug controls, indicating the irradiated nanoshells may increase cell membrane permeability and increase cellular uptake of the drug. This phenomena was further explored to enhance cellular uptake of siRNA, a large anionic therapeutic which cannot diffuse into cells easily. </p><p>This work advances the development of an injectable, optically-triggered delivery platform. With continued optimization and in vivo validation, this approach may offer an novel treatment option for cancer management.</p> / Dissertation

Solid phase extraction is one of the most widely used techniques to trap and release compounds in a solution. A hydrophobic substance will stick efficiently to a hydrophobic surface (the “like dissolves like” principle). With an introduced response (i.e. pH change), a responsive surface can change from hydrophobic to hydrophilic, weakening the hydrophobic substance’s attraction and thus facilitate in an easy removal. A surface has been prepared having a terminal anthranilic acid (AA) moiety on silica gel particles, microscope slides, and TLC plates in three steps. First, a vinyl group was attached to the surface. Then, this vinyl group was reacted to form a surface carboxylic acid group. Finally, the carboxylic acid group was converted to an amide group that linked to the silica surface. FT-IR, and elemental analysis were used to confirm each step of the synthesis. At low pHs the –COOH group on the AA moiety is neutral and intrahydrogen bonding keeps this moiety’s phenyl (hydrophobic) portion exposed to the surface. The effect has been investigated by measuring contact angles at various pH values. At higher pHs the AA’s carboxylic acid group becomes the charged carboxylate, rendering the surface hydrophilic. Substances can be trapped and released using this unique switching approach. 2-naphthol, for example, is hydrophobic and thus was trapped at lower pHs (pH 4) (hydrophobic surface) and released at higher pHs (pH 10) (hydrophilic surface) on this responsive surface

Children who have experienced developmental, social, or economic risks may benefit more from attending high-quality preschool intervention programs than their more advantaged peers; thus, programs that have delivered high-quality experiences may have served as a protective factor for these children to help reduce the achievement gap that has existed at school entry. The overarching purpose of this dissertation was to examine best practice in providing systemic early literacy interventions as a protective factor against school failure for young at-risk children. The three studies comprising this dissertation included analyses of systemic early literacy interventions for young children at risk of reading and school failure due to (a) developmental delays, (b) low socioeconomic status, or (c) English language learner status. Consistent with previous literature, the researcher found that children participating in a responsive early literacy intervention program were better prepared for kindergarten than were non-participating peers. Responsive early literacy interventions were defined as purposeful instruction designed to meet the educational needs of children by implementing an embedded-explicit or balanced approach to teaching. Attendance in high-quality early education programs - especially for children from disadvantaged backgrounds - was linked to lasting effects on indicators related to student achievement.

The majority of current internet traffic is based on TCP. With the emergence of new applications, especially new multimedia applications, however, UDP-based traffic is expected to increase. Furthermore, multimedia applications have sparkled the development of protocols responding to congestion while behaving differently from TCP. As a result, network traffc is expected to become more and more diverse. The increasing link capacity further stimulates new applications utilizing higher bandwidths of future. Besides the traffic diversity, the network is also evolving around new technologies. These trends in the Internet motivate our research work. In this dissertation, modeling and estimation techniques of heterogeneous traffic at a router are presented. The idea of the presented techniques is that if the observed queue length and packet drop probability do not match the predictions from a model of responsive (TCP) traffic, then the error must come from non-responsive traffic; it can then be used for estimating the proportion of non-responsive traffic. The proposed scheme is based on the queue length history, packet drop history, expected TCP and queue dynamics. The effectiveness of the proposed techniques over a wide range of traffic scenarios is corroborated using NS-2 based simulations. Possible applications based on the estimation technique are discussed. The implementation of the estimation technique in the Linux kernel is presented in order to validate our estimation technique in a realistic network environment.

No description available.

This thesis seeks to acknowledge the issues and challenges, as well as the opportunities and successes that continue to present for Māori learners accessing special education services in Aotearoa New Zealand. Year after year, strategic educational documents, policies and services are revisited, reviewed or restructured in order to effect a series of considered and realistic responses that are able to address the inequities that perpetuate for Māori learners. Discussions and debates specific to what needs to change, how this should be done, and who has the authority to decide, continue to be had. Perceptions vary between interested groups about the relevance and appropriateness of much of the research evidence that is drawn on to inform special education policy and practice directions for use with Māori learners. This research study investigates two key special education constructs; culturally responsive practice, and evidence based practice. The overall aims are to ascertain what Māori perceive to be the key components that comprise both of these individual terms; to determine if (and how) they are dissimilar or synonymous terms from a Māori perspective; and, to understand how these perceptions differ or are in tandem with special education (western) thinking. It is argued that these terms are regularly defined for Māori by non-Māori, without input or consultation from the former, and that this (in effect) perpetuates a cycle of special education service provision that is unable to respond adequately to, or connect culturally with, Māori realities. The scene is set wherein a three-circle evidence based practice framework that has been adopted by special education is used (in tandem with the Māori concept of mana), as the structure for selecting the research participants; all of whom are Māori / Māori affiliated. It is my contention that a range of Māori perspectives that are reflective of all of the three types of evidence that special education acknowledges is a worthy starting point for determining parallels and distinctions. From the three evidence domains of research, practice, and whānau, 18 leaders share their respective and collective knowledge, expertise, thoughts and wisdom about the two key constructs. What transpires throughout this study is the emergence of six strong components that are unanimously privileged by these leaders as critical to culturally responsive evidence based special education practice for Māori tamariki and whānau. These components are then drawn on to uncover a range of kaupapa Māori frameworks that are reflective of the participants’ discourses.

In this work, the development of temperature- and protein-responsive sensor materials based on biocompatible, inverse hydrogel opals (IHOs) is presented. With these materials, large biomolecules can be specifically recognised and the binding event visualised. The preparation of the IHOs was performed with a template process, for which monodisperse silica particles were vertically deposited onto glass slides as the first step. The obtained colloidal crystals with a thickness of 5 μm displayed opalescent reflections because of the uniform alignment of the colloids. As a second step, the template was embedded in a matrix consisting of biocompatible, thermoresponsive hydrogels. The comonomers were selected from the family of oligo(ethylene glycol)methacrylates. The monomer solution was injected into a polymerisation mould, which contained the colloidal crystals as a template. The space in-between the template particles was filled with the monomer solution and the hydrogel was cured via UV-polymerisation. The particles were chemically etched, which resulted in a porous inner structure. The uniform alignment of the pores and therefore the opalescent reflection were maintained, so these system were denoted as inverse hydrogel opals. A pore diameter of several hundred nanometres as well as interconnections between the pores should facilitate a diffusion of bigger (bio)molecules, which was always a challenge in the presented systems until now. The copolymer composition was chosen to result in a hydrogel collapse over 35 °C. All hydrogels showed pronounced swelling in water below the critical temperature. The incorporation of a reactive monomer with hydroxyl groups ensured a potential coupling group for the introduction of recognition units for analytes, e.g. proteins. As a test system, biotin as a recognition unit for avidin was coupled to the IHO via polymer-analogous Steglich esterification. The amount of accessible biotin was quantified with a colorimetric binding assay. When avidin was added to the biotinylated IHO, the wavelength of the opalescent reflection was significantly shifted and therefore the binding event was visualised. This effect is based on the change in swelling behaviour of the hydrogel after binding of the hydrophilic avidin, which is amplified by the thermoresponsive nature of the hydrogel. A swelling or shrinking of the pores induces a change in distance of the crystal planes, which are responsible for the colour of the reflection. With these findings, the possibility of creating sensor materials or additional biomolecules in the size range of avidin is given. / In dieser Arbeit wird die Entwicklung von temperatur- und proteinresponsiven Sensormaterialien auf Basis von biokompatiblen, inversen Hydrogelopalen (IHO) vorgestellt, mit welchen die spezifische Erkennung größerer Biomoleküle visuell ausgelesen werden kann. Die Darstellung der IHOs erfolgte mittels Templatverfahren, bei dem im ersten Schritt monodisperse Silicapartikel vertikal auf Objektträger abgeschieden wurden. Die so erhaltenen Kolloidkristalle mit einer Dicke von 5 μm zeigten opaleszente Reflexionen aufgrund der gleichförmigen Anordnung der Partikel. Im zweiten Schritt wurde das Templat in eine Matrix aus biokompatiblen, thermoresponsiven Hydrogelen eingebettet. Die Comonomere wurden aus der Familie der Oligo(ethylenglykol)methacrylate ausgewählt. Zur Synthese des Hydrogels wurde die Monomerlösung in eine Polymerisationsform injiziert, welche die Kolloidkristalle als Templat beinhaltete. Die Zwischenräume der Templatpartikel wurden mit der Monomerlösung gefüllt und das Hydrogelnetzwerk per UV-Polymerisation erhalten. Die Templatpartikel wurden anschließend nasschemisch heraus gelöst, so dass eine poröse innere Struktur erhalten wurde. Die regelmäßige Anordnung der Poren und damit die opaleszenten Reflexionen wurden dabei beibehalten, so dass diese Systeme als inverse Hydorgelopale bezeichnet werden. Ein Porendurchmesser von mehreren hundert Nanometer, sowie durchgängige Verbindungskanäle zwischen den einzelnen Poren sollten eine Diffusion von großen (Bio)molekülen erleichtern, was bei bisherigen Systemen ein Problem darstellte. Die Copolymerzusammensetzung wurde dabei so gewählt, dass ein Kollaps des Hydrogels über 35 °C stattfand. Alle Hydrogele zeigten ausgeprägte Quellung in Wasser unterhalb der kritischen Temperatur. Der Einbau von reaktiven Comonomeren mit Hydroxylgruppen gewährleistete dabei die Funktionalisierbarkeit des Hydrogels mit Erkennungsgruppen für entsprechende Analytmoleküle, wie z.B. Proteine. Als Testsystem wurde Biotin als Erkennungseinheit für Avidin in das Hydrogel mittels polymeranaloger Steglich Veresterung eingebaut. Die Menge an zugänglichem Biotin wurde dabei per colorimetrischem Bindungsassay quantifiziert. Dabei zeigte sich, dass sich die Wellenlänge der Reflexion nach Zugabe von Avidin zum biotinylierten inversen Hydrogelopal signifikant verschob und damit das Bindungsereignis visuell auslesbar ist. Dieser Effekt beruht auf dem veränderten Quellungsverhalten des Hydrogels nach Bindung des hydrophilen Proteins Avidin in Wasser, welches durch den thermosresponsiven Charakter des Hydrogels verstärkt ist. Ein Aufweiten oder Schrumpfen der Poren ändert die Abstände der gleichmäßig angeordneten Poren, welche für die Farbe des inversen Opals verantwortlich sind. Auf Basis dieser Erkenntnisse lassen sich möglicherweise Sensormaterialen für die Erkennung weiterer Biomoleküle in der Größenordnung von Avidin erstellen.

The goal of this research is to develop a method of objectively comparing and optimizing the performance of demand-responsive transportation systems in heterogeneous environments. Demand-responsive transportation refers to modes of transportation that do not follow fixed routes or schedules, including taxis, paratransit, deviated-route services, ride sharing as well as other modes. Heterogeneous environments are transportation environments in which streets do not follow regular patterns, passenger behavior is difficult to model, and transit schedules and layouts are non-uniform. An example of a typical heterogeneous environment is a modern suburb with non-linear streets, low pedestrian activity, and infrequent or sparse transit service. The motivation for this research is to determine if demand-responsive transportation can be used to improve customer satisfaction and reduce operating costs in suburban and low-density urban areas where fixed-route transportation may be inefficient. This research extends existing comparison and optimization techniques that are designed to work in homogeneous environments. Homogeneous environments refer to transportation systems where the streets follow regular and repeating patterns, passengers are evenly distributed throughout the system, and the transit system is easily modeled. The performance of systems with these characteristics can be approximated with closed-form analytical expressions representing passenger travel times, vehicle distances traveled, and other performance indicators. However, in the low-density urban areas studied in this research, the street patterns and transit schedules are irregular and passenger behavior is difficult to model. In these areas, analytical solutions cannot be found. Instead, this research develops a simulation-based approach to compare and optimize performance in these heterogeneous environments. Using widely-available route-planning tools, open-source transit schedules, and detailed passenger data, it is possible to simulate the behavior of transit vehicles and passengers to such an exacting degree that analytical solutions are not needed. A major technical contribution of this research is the development of a demand-responsive transportation simulator to analyze performance of demand-responsive systems in heterogeneous environments. The simulator combines several open-source tools for route planning with a custom-built demand-responsive vehicle and passenger-itinerary optimizer to simulate individual vehicles and passengers within a large system. With knowledge of the street network, the transit schedule, passenger locations, and trip request times, the simulator will output exact passenger transit times, passenger travel distances, vehicle travel distance, and other performance indicators for a particular transportation setup in a given area. The simulator is used to develop a method of comparing various demand-responsive and fixed-route systems. By predefining a set of performance indicators, such as passenger travel time and operating cost, the simulator can be used to ascertain the performance of a wide array of transportation systems. Comparing the weighted cost of each type of system permits a transportation engineer or planner to determine what type of system will provide the best results in a given area. The simulator is extended to assist in optimization of the demand-responsive transportation system layout. A key problem that needs to be solved when implementing a demand-responsive system is to determine the size, shape, and location of the demand-responsive coverage areas, i.e., the areas in which passengers are eligible for demand-responsive transportation. Using a particle swarm optimization algorithm and the simulation-based comparison technique, the optimal size and shape for a demand-responsive coverage area can be determined. The efficacy of the comparison and optimization techniques is demonstrated within the city of Atlanta, GA. It is shown that for certain areas of the city of Atlanta, demand-responsive transportation is more efficient than the currently implemented fixed-route system. Depending on the objective of the transportation planner, passenger satisfaction as well as operating costs can be improved by implementing a demand-responsive system in certain low-density areas. The techniques introduced in this research, and the simulation tool developed to implement those techniques, provide a repeatable, accurate, and objective method with which to optimize and compare demand-responsive transportation systems in heterogeneous environments.

Mångfalden av enheter för webbanvändning ökar, men det finns fortfarande webbplatser som utvecklas med PC:s som enda prioritet. Responsiv webbdesign erbjuder nya möjligheter till webbutveckling eftersom en responsiv webbplats är anpassad till samtliga enheter på marknaden. Området har förvisso fått stort genomslag, men det är fortfarande nytt och relativt outforskat. Det finns också endel utmaningar med responsiv webbdesign som kan vara svåra att bemöta. Uppsatsen kartlägger utmaningar som lyfts fram i vetenskaplig litteratur, och bekräftar eller dementerar samt kompletterar kartlagda utmaningar genom enempirisk studie. I uppsatsens slutsats introduceras ett ramverk med utmaningar inom responsiv webbdesign. / The variety of devices for web use increases, but some web sites are still being developed with PC:s as their only priority. Responsive web design is a way of developing web sites for all devices on the market, and therefore creating new opportunities for web development. The area is still new and relatively unexplored, and there are challenges that can be difficult to address. The thesis maps out challenges found in scientific literature, and confirmes or denies and supplements identified challenges through an empirical study. The thesis concludes with an introduction to a framework with challenges in responsive webdesign.

Scholars and policy makers alike argue that leaders of democracies should find it in their interest to provide high levels of social services due to a fear of being voted out of office. Yet, I find that Africa's newer democracies provide levels of social services strikingly similar to what the continent's existing non-democracies supply. This dissertation seeks to explain why this is the case. I start by exploring the determinants of Africa's most recent wave of democratization, and find that much of Africa's 1990s democratic wave can be attributed to changes in foreign circumstances rather than from pressures from domestic democratic movements. I argue democratization has become disassociated with social services on the continent because of this exogenous nature of political liberalization. Rather than institutionalizing electoral incentives to provide social services, leadership of exogenously derived democracies become principally accountable to the foreign actors for whom political change was meant to appease. However, foreign actors are effectively unable and unwilling to demand political reforms that will institutionalize a more responsive democracy. This dynamic threatens any electoral incentive a ruling party might have to produce higher levels of social services. I test this argument quantitatively and find support for the notion that exogeneity of political change has dampened the impact that democratization has had on social service delivery in Africa. Additionally, through in-country, qualitative fieldwork I examine how citizens demand social services and how the government responds to such demands in Zambia, a country whose democratization was heavily influenced by foreign pressure. There, I found that while there were important initial strides made by Zambia's post-transition government to institutionalize a higher level of responsiveness in social services, later erosions in Zambia's checks and balances undermined these gains. Finally, using Afrobarometer's cross-national survey data, I explore what impact foreign influenced democratization has on citizens' attachment to and satisfaction with democracy. I find that exogenously derived democratization has a small negative impact on people's attachment to democracy and satisfaction with the way democracy works in their country. I conclude by discussing some of the policy implications of these findings.