Development of polymeric drug delivery vehicles for targeted cancer therapy

The aim of my Ph. D. thesis is to generalize a method for targeted anti-cancer drug delivery. Hydrophilic polymer-drug conjugates involve complicated synthesis; drug-encapsulated polymeric nanoparticles limit the loading capability of payloads. This thesis introduces the concept of nanoconjugates to overcome difficulties in synthesis and formulation. Drugs with hydroxyl group are able to initiate polyester synthesis in a regio- and chemo- selective way, with the mediation of ligand-tunable Zinc catalyst. Herein, three anti-cancer drugs are presented to demonstrate the high efficiency and selectivity in the method (Chapter 2-4). The obtained particles are stable in salt solution, releasing drugs over weeks in controlled manner. With the conjugation of aptamer, particles are capable to target prostate cancer cells in vitro. These results open the gateway to evaluate the in vivo efficacy of nanoconjugates for target cancer therapy (Chapter 5). Mechanism study of the polymerization leads to the discovery of chemosite selective synthesis of prodrugs with acrylate functional groups. Functional copolymer-drug conjugates will expand the scope of nanoconjugates (Chapter 6). Liposome-aptamer targeting drug delivery vehicle is well studied to achieve reversible cell-specific delivery of non-hydoxyl drugs e.g. cisplatin (Chapter 7). New monomers and polymerization mechanisms are explored for polyester in order to synthesize nanoconjugates with variety on properties (Chapter 8). Initial efforts to apply this type of prodrugs will be focused on the preparation of hydrogels for stem cell research (Chapter 9).

Governance and community capitals : understanding how governance has worked in three faith-based schools in the Western Highlands of Papua New Guinea

This thesis, titled Governance and Community Capitals, explores the kinds of practical processes that have made governance work in three faith-based schools in the Western Highlands of Papua New Guinea (PNG). To date, the nation of PNG has been unable to meet its stated educational goals; however, some faith-based primary schools have overcome educational challenges by changing their local governance systems. What constitutes good governance in developing countries and how it can be achieved in a PNG schooling context has received very little scholarly attention. In this study, the subject of governance is approached at the nexus between the administrative sciences and asset-based community development. In this space, the researcher provides an understanding of the contribution that community capitals have made to understandings of local forms of governance in the development context. However, by and large, conceptions of governance have a history of being positioned within a Euro-centric frame and very little, if anything is known about the naming of capitals by indigenous peoples. In this thesis, six indigenous community capitals are made visible, expanding the repertoire of extant capitals published to date. The capitals identified and named in this thesis are: Story, Wisdom, Action, Blessing, Name and Unity. In-depth insights into these capitals are provided and through the theoretical idea of performativity, the researcher advances an understanding of how the habitual enactment of the practical components of the capitals made governance work in this unique setting. The study draws from a grounded and appreciative methodology and is based on a case study design incorporating a three-stage cycle of investigation. The first stage tested the application of an assets-based method to documentary sources of data including most significant change stories, community mapping and visual diaries. In the second stage, a group process method relevant to a PNG context was developed and employed. The third stage involved building theory from case study evidence using content analysis, language and metaphorical speech acts as guides for complex analysis. The thesis demonstrates the contribution that indigenous community capitals can make to understanding local forms of governance and how PNG faith-based schools meet their local governance challenges.

Radiogenic isotopes in the Mediterranean Sea: water mass exchange and precessional variability during the Messinian

During the late Miocene, exchange between the Mediterranean Sea and Atlantic Ocean changed dramatically, culminating in the Messinian Salinity Crisis (MSC). Understanding Mediterranean-Atlantic exchange at that time could answer the enigmatic question of how so much salt built up within the Mediterranean, while furthering the development of a framework for future studies attempting to understand how changes may have impacted global thermohaline circulation. Due to their association with specific water masses at different scales, radiogenic Sr, Pb, and Nd isotope records were generated from various archives contained within marine deposits to endeavour to understand better late Miocene Mediterranean-Atlantic exchange. The archives used include foraminiferal calcite (Sr), fish teeth and bone (Nd), dispersed authigenic ferromanganese oxyhydroxides (Nd, Pb), and a ferromanganese crust (Pb). The primary focus is on sediments preserved at one end of the Betic corridor, a gateway that once connected the Mediterranean to the Atlantic through southern Spain, although other locations are investigated. The Betic gateway terminated within several marginal sub-basins before entering the Western Mediterranean; one of these is the Sorbas Basin, a well-studied location whose sediments have been astronomically tuned at high temporal resolution, providing the necessary age control for sub-precessional resolution records. Since the climatic history of the Mediterranean is strongly controlled by precessional changes in regional climate, the aim was to produce records at high (sub-precessional) temporal resolution, to be able to observe clearly any precessional cyclicity driven by regional climate which could be superimposed over longer trends. This goal was achieved for all records except the ferromanganese crust record. The 87Sr/86Sr isotope record (Ch. 3) shows precessional frequency excursions away from the global seawater curve. As precessional frequency oscillations are unexpected for this setting, a numerical box model was used to determine the mechanisms causing the excursions. To enable parameterisation of model variables, regional Sr characteristics, data from general circulation model HadCM3L, and new benthic foraminiferal assemblage data are employed. The model results imply that the Sorbas Basin likely had a positive hydrologic budget in the late Miocene, very different to that of today. Moreover, the model indicates that the mechanism controlling the Sr isotope ratio of Sorbas Basin seawater was not restriction, but a lack of density-driven exchange with the Mediterranean. Beyond improving our understanding of how marginal Mediterranean sub-basins may evolve different isotope signatures, these results have implications for astronomical tuning and stratigraphy in the region, findings which are crucial considering the geological and climatic history of the late Miocene Mediterranean is based entirely on marginal deposits. An improved estimate for the Nd isotope signature of late Miocene Mediterranean Outflow (MO) was determined by comparing Nd isotope signatures preserved in the deeper Alborán Sea at ODP Site 978 with literature data as well as the signature preserved in the Sorbas Basin (Ch. 4; -9.34 to -9.92 ± 0.37 εNd(t)). It was also inferred that it is unlikely that Nd isotopes can be used reliably to track changes in circulation within the shallow settings characteristic of the Mediterranean-Atlantic connections; this is significant in light of a recent publication documenting corridor closure using Nd isotopes. Both conclusions will prove useful for future studies attempting to understand changes in Mediterranean-Atlantic exchange. Excursions to high values, with precessional frequency, are also observed in the radiogenic Pb isotope record for the Sorbas Basin (Ch. 5). Widening the scope to include locations further away from the gateways, records were produced for late Miocene sections on Sicily and Northern Italy, and similar precessional frequency cyclicity was observed in the Pb isotope records for these sites as well. Comparing these records to proxies for Saharan dust and available whole rock data indicates that, while further analysis is necessary to draw strong conclusions, enhanced dust production during insolation minima may be driving the observed signal. These records also have implications for astronomical tuning; peaks in Pb isotope records driven by Saharan dust may be easier to connect directly to the insolation cycle, providing improved astronomical tuning points. Finally, a Pb isotope record derived using in-situ laser ablation performed on ferromanganese crust 3514-6 from the Lion Seamount, located west of Gibraltar within the MO plume, has provided evidence that plume depth shifted during the Pliocene. The record also suggests that Pb isotopes may not be a suitable proxy for changes in late Miocene Mediterranean-Atlantic exchange, since the Pb isotope signatures of regional water masses are too similar. To develop this record, the first published instance of laser ablation derived 230Thexcess measurements are combined with 10Be dating.

Hyperlinks in e-books : expanding the functionality of end-notes

With its powerful search engines and billions of published pages, the Worldwide Web has become the ultimate tool to explore the human experience. But, despite the advent of the digital revolution, e-books, at their core, have remained remarkably similar to their printed siblings. This has resulted in a clear dichotomy between two ways of reading: on one side, the multi-dimensional world of the Web; on the other, the linearity of books and e-books. My investigation of the literature indicates that the focus of attempts to merge these two modes of production, and hence of reading, has been the insertion of interactivity into fiction. As I will show in the Literature Review, a clear thrust of research since the early 1990s, and in my opinion the most significant, has concentrated on presenting the reader with choices that affect the plot. This has resulted in interactive stories in which the structure of the narrative can be altered by the reader of experimental fiction. The interest in this area of research is not surprising, as the interaction of readers with the fabric of the narrative provides a fertile ground for exploring, analysing, and discussing issues of plot consistency and continuity. I found in the literature several papers concerned with the effects of hyperlinking on literature, but none about how hyperlinked material and narrative could be integrated without compromising the narrative flow as designed by the author. It led me to think that the researchers had accepted hypertextuality and the linear organisation of fiction as being antithetical, thereby ignoring the possibility of exploiting the first while preserving the second. All the works I consulted were focussed on exploring the possibilities provided to authors (and readers) by hypertext or how hypertext literature affects literary criticism. This was true in earlier works by Landow and Harpold and remained true in later works by Bolter and Grusin. To quote another example, in his book Hypertext 3.0, Landow states: “Most who have speculated on the relation between hypertextuality and fiction concentrate [...] on the effects it will have on linear narrative”, and “hypertext opens major questions about story and plot by apparently doing away with linear organization” (Landow, 2006, pp. 220, 221). In other words, the authors have added narrative elements to Web pages, effectively placing their stories in a subordinate role. By focussing on “opening up” the plots, the researchers have missed the opportunity to maintain the integrity of their stories and use hyperlinked information to provide interactive access to backstory and factual bases. This would represent a missing link between the traditional way of reading, in which the readers have no influence on the path the author has laid out for them, and interactive narrative, in which the readers choose their way across alternatives, thereby, at least to a certain extent, creating their own path. It would be, to continue the metaphor, as if the readers could follow the main path created by the author while being able to get “sidetracked” into exploring hyperlinked material. In Hypertext 3.0, Landow refers to an “Axial structure [of hypertext] characteristic of electronic books and scholarly books with foot-and endnotes” versus a “Network structure of hypertext” (Landow, 2006, p. 70). My research aims at generalising the axial structure and extending it to fiction without losing the linearity at its core. In creative nonfiction, the introduction of places, scenes, and settings, together with characterisation, brings to life the facts without altering them; while much fiction draws on facts to provide a foundation, or narrative elements, for the work. But how can the reader distinguish between facts and representations? For example, to what extent do dialogues and perceptions present what was actually said and thought? Some authors of creative nonfiction use end-notes to provide comments and citations while minimising disruption the flow of the main text, but they are limited in scope and constrained in space. Each reader should be able to enjoy the narrative as if it were a novel but also to explore the facts at the level of detail s/he needs. For this to be possible, end-notes should provide a Web-like way of exploring in more detail what the author has already researched. My research aims to develop ways of integrating narrative prose and hyperlinked documents into a Hyperbook. Its goal is to create a new writing paradigm in which a story incorporates a gateway to detailed information. While creative nonfiction uses the techniques of fictional writing to provide reportage of actual events and fact-based fiction illuminates the affectual dimensions of what happened (e.g., Kate Grenville’s The Secret River and Hilary Mantel’s Wolf Hall), Hyperbooks go one step further and link narrative prose to the details of the events on which the narrative is based or, more in general, to information the reader might find of interest. My dissertation introduces and utilises Hyperbooks to engage in two parallel types of investigation Build knowledge about Italian WWII POWs held in Australia and present it as part of a novella in Hyperbook format. Develop a new piece of technology capable of extending the writing and reading process.

Virtual Enterprise Process Management: An Application to Industrial Maintenance

Part 2: Behaviour and Coordination

Pool Irradiator Safety Review for Genesis-II Systems

This report examines the Genesis II irradiator made by Gray*Star Incorporated, Mississippi Department of Health radiation safety regulations, and Nuclear Regulatory Commission (NRC) inspection guidelines for irradiators. The purpose for this report is to evaluate any hazards which may lead to a catastrophic water loss, evaluate protective action distances during a reduced shielding situation, and evaluate the safety engineering measures incorporated by Mississippi and Federal regulations to ensure the mitigation of risk for pool irradiators. Due to safeguard controls prohibiting release of precise data on emergency response measures and radioactivity of the isotopes utilized this report will be focused on regulations mandating specific engineering controls and manufacturer recommended guidelines for best practices.

Binocular functional architecture for detection of contrast-modulated gratings

Combination of signals from the two eyes is the gateway to stereo vision. To gain insight into binocular signal processing, we studied binocular summation for luminance-modulated gratings (L or LM) and contrast-modulated gratings (CM). We measured 2AFC detection thresholds for a signal grating (0.75 c/deg, 216msec) shown to one eye, both eyes, or both eyes out-of-phase. For LM and CM, the carrier noise was in both eyes, even when the signal was monocular. Mean binocular thresholds for luminance gratings (L) were 5.4dB better than monocular thresholds - close to perfect linear summation (6dB). For LM and CM the binocular advantage was again 5-6dB, even when the carrier noise was uncorrelated, anti-correlated, or at orthogonal orientations in the two eyes. Binocular combination for CM probably arises from summation of envelope responses, and not from summation of these conflicting carrier patterns. Antiphase signals produced no binocular advantage, but thresholds were about 1-3dB higher than monocular ones. This is not consistent with simple linear summation, which should give complete cancellation and unmeasurably high thresholds. We propose a three-channel model in which noisy monocular responses to the envelope are binocularly combined in a contrast-weighted sum, but also remain separately available to perception via a max operator. Vision selects the largest of the three responses. With in-phase gratings the binocular channel dominates, but antiphase gratings cancel in the binocular channel and the monocular channels mediate detection. The small antiphase disadvantage might be explained by a subtle influence of background responses on binocular and monocular detection.

Predicamento de seguridad yemení

Con el inicio del periodo Post-Guerra Fría el Sistema Internacional comienza a experimentar un incremento en el fortalecimiento de su componente social; la Sociedad de Estados alcanza un mayor nivel de homogenización, el estado, unidad predominante de esta, comienzan atravesar una serie de transformaciones que obedecerán a una serie de cambios y continuidades respecto al periodo anterior. Desde la perspectiva del Realismo Subalterno de las Relaciones Internacionales se destacan el proceso de construcción de estado e inserción al sistema como las variables que determinan el sentimiento de inseguridad experimentado por las elites estatales del Tercer Mundo; procesos que en el contexto de un nuevo y turbulento periodo en el sistema, tomara algunas características particulares que darán un sentido especifico al sentimiento de inseguridad y las acciones a través de las cuales las elites buscan disminuirlo. La dimensión externa del sentimiento de inseguridad, el nuevo papel que toma la resistencia popular como factor determinante del sentimiento de inseguridad y de la cooperación, así como del conflicto, entre los miembros de la Sociedad Internacional, la inserción como promotor de estrategias de construcción de Estado, son alguno de los temas puntuales, que desde la perspectiva subalterna, parecen salir a flote tras el análisis del sistema en lo que se ha considerado como el periodo Post-Guerra Fría. En este sentido Yemen, se muestra como un caso adecuado no solo para poner a prueba las postulados de la teoría subalterna, veinte años después de su obra más prominente (The third world security Predicament), escrita por M. Ayoob, sino como un caso pertinente que permite acercarse más a la comprensión del papel del Tercer Mundo al interior de la Sociedad Internacional de Estados.

Aprendizaje activo

El Centro de Enseñanza Aprendizaje de la Universidad del Rosario (cea-ur), acorde con su compromiso por el mejoramiento continuo y la búsqueda de la innovación en los procesos de enseñanza-aprendizaje, pone a disposición de la comunidad académica el Boletín Reflexiones Pedagógicas. Esta colección presentará diversas alternativas para mejorar nuestros procesos didácticos y fortalecer los procesos de aprendizaje de nuestros estudiantes, de una manera sencilla y fácil de entender. En este primer número se presenta el tema de aprendizaje activo centro de nuestro proyecto educativo enunciado en el pei 2014.En él encontrarán no solo a qué se refiere este tipo de aprendizaje, sino también la descripción de algunas estrategias para desarrollarlo y referencias para profundizar en este tema.

América Latina y el Caribe: Variables de competitividad para la dinámica empresarial 2007 - 2014

Este estudio realiza una categorización regional de los países en América Latina con respecto de las categorizaciones globales teniendo en cuenta los índices de competitividad, crecimiento económico y desarrollo humano. El objetivo es actualizar los análisis sobre la situación regional de forma cuantitativa involucrando el grado de asimetría en la competitividad. Esta relación entre el posicionamiento global y regional ha influenciado directamente la evolución del tejido empresarial

Del sincretismo ideológico en la reflexión económica novogranadina: política económica y economía política en Cartagena de Indias, 1800-1809

De 1800 a 1808, diferentes comerciantes y funcionarios reales en Cartagena de Indias solicitaron la ejecución de una política económica que les permitiera sobrevenir los bloqueos portuarios generados por las guerras que España libró en aquellos años: el comercio neutral. Al tomar la historia de las discusiones alrededor de esta política comercial como una puerta de entrada a la reflexión sobre economía política en el Nuevo Reino de Granada, este artículo busca explorar los fundamentos teóricos del comercio neutral. Tres momentos de la discusión sobre la medida se ponen de relieve en el artículo: 1800, 1805 y 1808. En cada uno de ellos, defensores y opositores del comercio neutral argumentaron a favor y en contra sustentados en dos premisas fundamentales. Primera, la observación de la aplicación de políticas económicas en territorios vecinos era un método válido para analizar su pertinencia y, segunda, un comercio activo era inexcusable para alcanzar la “felicidad pública” del reino. Estas dos premisas y su finalidad pragmática señalan el sincretismo ideológico que informó los fundamentos teóricos del reformismo borbónico, del cual emergió el comercio neutral. Este artículo propone una respuesta a la pregunta sobre la naturaleza de la reflexión económica novogranadina al situarla dentro de su intención práctica, esto es, la formulación y evalución de políticas económicas, y al sugerir que dentro de estos límites pragmáticos se encuentran nuevas voces, nuevos documentos y una nueva propuesta historiográfica sobre la economía política en el Nuevo Reino de Granada.

Caracterización y prevalencia del compromiso ocular en pacientes con enfermedad autoinmune y autoinflamatoria en un centro de referencia reumatológica en Colombia entre los años 2000 a 2015

RESUMEN Objetivo: Estimar la prevalencia de las diferentes enfermedades oftalmológicas que aparecen en el contexto de una enfermedad autoinmune (EAI) en pacientes de un centro de referencia reumatológica en Colombia, según características clínicas y sociodemográficas durante un período de 15 años, comprendido entre los años 2000 a 2015. Métodos: Se realizó un estudio descriptivo, observacional de prevalencia. El tipo de muestreo fue aleatorio estratificado con asignación proporcional en el programa Epidat 3.4. Los datos se analizaron en el programa SPSS v22.0 y se realizó análisis univariado de las variables categóricas, para las variables cuantitativas se realizaron medidas de tendencia central. Resultados: De 1640 historias clínicas revisadas, se encontraron 634 pacientes (38,65%) con compromiso ocular. Si excluimos los pacientes con SS, que por definición presentan ojo seco, 222 pacientes (13,53%) presentaron compromiso oftalmológico. Del total de pacientes, el 83,3% fueron mujeres. La AR fue la enfermedad autoinmune con mayor compromiso oftalmológico con 138 pacientes (62,2%), y en último lugar la sarcoidosis con 1 solo paciente afectado. La QCS fue la manifestación más común en todos los grupos diagnósticos de EAI, con 146 pacientes (63,5%). De 414 pacientes con Síndrome de Sjögren (SS) y QCS 8 presentaron compromiso ocular adicional, siendo la uveítis la segunda patología ocular asociada en pacientes con SS y la primera causa en las espondiloartropatias (71,4 %). Los pacientes con catarata (4,1%) presentaron la mayor prevalencia de uso de corticoide (88.8%). De 222 pacientes, 28 (12,6%) presentaron uveítis. Del total de pacientes, 16 (7,2%) presentaron maculopatía por antimalaráricos y 6 (18,75%) de los pacientes con LES. Los ANAS se presentaron en el 100% los pacientes con trastorno vascular de la retina. Los pacientes con epiescleritis presentaron la mayor proporción de positivización de anticuerpos anti-DNA. La EAI que más presentó epiescleritis fue LES con 4 pacientes (12,5%) El 22% de paciente con anticuerpos anti-RNP presentaron escleritis y 32,1% de los pacientes con uveítis presentaron HLA-B27 positivo. Las manifestaciones oftalmológicas precedieron a las sistémicas entre un 11,1% y un 33,3% de los pacientes. Conclusión: Las enfermedades oculares se presentan con frecuencia en los pacientes colombianos con EAI (38.65%), siendo la AR la enfermedad con mayor compromiso ocular (62,2%) y la QCS la enfermedad ocular con mayor prevalencia en todas las EAI (63,5%). La uveítis se presentó en 28 pacientes (12,6%). Las manifestaciones oftalmológicas pueden preceder a las sistémicas. El examen oftalmológico debe ser incluido en los pacientes con EAI, por ser la enfermedad ocular una comorbilidad frecuente. Adicionalmente, los efectos oftalmológicos de las medicaciones sistémicas utilizadas en EAI deben ser estrechamente monitorizados, durante el curso del tratamiento.

Quality of Judgment Assessment

The intersection of Artificial Intelligence and The Law stands for a multifaceted matter, and its effects set the advances on culture, organization, as well as the social matters, when the emergent information technologies are taken into consideration. From this point of view, the weight of formal and informal Conflict Resolution settings should be highlighted, and the use of defective data, information or knowledge must be emphasized. Indeed, it is hard to do it with traditional problem solving methodologies. Therefore, in this work the focus is on the development of decision support systems, in terms of its knowledge representation and reasoning procedures, under a formal framework based on Logic Programming, complemented with an approach to computing centered on Artificial Neural Networks. It is intended to evaluate the Quality-of-Judgments and the respective Degree-of-Confidence that one has on such happenings.

Analisi Sperimentale delle Prestazioni di Nodi Wireless LoRa in Presenza di Interferente

L’obiettivo dell’Internet of Things (IoT), come suggerisce il nome, è quello di connettere oggetti (spesso alimentati a batteria) alla rete Internet per poterne avere un controllo da remoto. Lo sviluppo di questa tecnologia prevede la progettazione di dispositivi che abbiano: un basso costo per unità, una durata della batteria sufficientemente lunga (anche dell’ordine di anni) quindi bassi consumi e la possibilità di realizzare un’ampia rete che possa supportare tante unità. Per questo elaborato è stata utilizzata la tecnologia LoRa, creata da Semtech. Essa lavora nelle frequenze ISM designate per le varie zone geografiche del mondo, presenta un Livello Fisico personalizzato ispirato alla modulazione CSS e un Livello MAC che si basa sul protocollo ALOHA puro. Lo scopo di questo elaborato è realizzare delle misure delle prestazioni in ambiente indoor tramite l’utilizzo di due nodi (End Devices) e un gateway. Sono state sviluppate due applicazioni Java per realizzare la comunicazione tra i dispositivi. Le misure sono state realizzate inizialmente con un nodo singolo, per osservarne il tasso di perdita di pacchetti (packet loss rate) e l’attenuazione di potenza sul canale (channel loss). Successivamente sono state inviate trasmissioni da entrambi i nodi, prima separatamente e poi in contemporanea, per valutare l’interferenza tra invii di messaggi con uguali impostazioni nello stesso canale. Per fare ciò è stato utilizzato un modello della comunicazione di canale che tiene conto del path loss e dello shadowing log-normale. I risultati hanno mostrato che con un solo nodo si tratta di una tecnologia affidabile. Per quanto riguarda i risultati delle misure con interferente è emersa una differenza con i valori attesi fino al 20%. Nell’elaborato vengono discussi i risultati ottenuti e possibili sviluppi futuri per questo tipo di sperimentazione.

Nodi sensori LoRaWAN a micropotenze: progettazione hardware, firmware e a livello di applicazione

L'elaborato parte da una scheda di sviluppo commerciale per arrivare a realizzare una rete LoRaWAN comprensiva di End-Node, Gateway e Application Server. In maniera specifica, l'elaborato affronta il problema della progettazione di end-node a micropotenze. Dopo aver studiato e collaudato la piattaforma di sviluppo, è stata affrontata la problematica dell'ottimizzazione energetica a diversi livelli: scelta di componenti con correnti di perdita estremamente ridotte, tecniche di power gating temporizzato, comportamento adattativo del nodo, impostazione dei consumi del nodo mediante i server della rete. L'elaborato presenta infine il layout del PCB progettato, pronto per la fabbricazione, insieme a stime del tempo di vita dell'end-node in funzione della frequenza di trasmissione e della capacità delle batterie utilizzate.