Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / RNA potently regulates gene expression. However, the utility of RNA has been limited by the ability to efficiently deliver it to specific cells in vivo. In vivo RNA delivery is challenging; vehicles must avoid phagocytosis in the bloodstream, reach the target tissue, and get into, and out of, an endosome, all without setting off an unwanted immune response. Despite these challenges, nanoparticles have delivered siRNA to hepatocytes after intravenous injections as low as 0.001 mg/kg. By contrast, efficient, durable, and robust silencing in other cell types has remained challenging. Herein we describe 7C I, a low molecular weight polymeric nanoparticle that delivers siRNA to endothelial cells in vivo at doses as low as 0.017 mg/kg. 7C1 nanoparticles reduced target mRNA expression for more than three weeks after a single injection, and delivered five siRNAs concurrently in vivo. Notably, 7C I transfects endothelial cells at low doses without significantly reducing gene expression in hepatocytes or immune cells. 7C I was optimized for stability and consistency, and used to study inflammation, cardiovascular disease, emphysema, primary tumor growth, and metastasis in labs across the United States. These data demonstrate that 7C I can be used to potently modify the expression of multiple endothelial genes in vivo. / by James E. Dahlman. / Ph. D.

<p>This work studies constraint mechanisms in frame-based knowledge representation systems with the aim of improving the knowledge modelling abilities of the TrollCreek system. TrollCreek is an implementation of Creek, an architecture for case based reasoning (CBR) that uses an explicit frame-based knowledge model to guide the CBR process. The objective of this project is to develop a constraint mechanism for TrollCreek. In doing this the earlier Lisp implementation of Creek and four other frame-based systems are examined with emphasize on their constraint mechanisms. Based on these systems a constraint mechanism for TrollCreek is discussed and specified. The part of the mechanism considered most central is implemented and evaluated.</p>

<p>In testing the viability of automatic knowledge-acquisition, using simple techniques and brute force on the Internet, a system was implemented in Java. Techniques from both multi-agent system and swarm intelligence paradigms were used to structure the system, improve searches, increase stability and increase modularity. The system presented relies on using existing search-engines to find texts on the World Wide Web, containing a user-specified key-word. Knowledge is identified in the texts using key-sentences, terms related to the key-word becomes new key-words in an incremental search. The result is expressed as sentences in a KR-language. The answers from a run were often interesting and surprising, and gave information beyond an encyclopedic scope, even if the answers often contained false information. The results of the implemented system verified the viability of both the designed framework and the theory behind it.</p>

<p>The work in this thesis is about natural language processing and understanding, within the context of artificial intelligence research. What was attempted to achieve here was to investigate how meaning is contained in language, particularly with respect to how that information is encoded and how it can be decoded, or extracted. The aspects deemed most relevant for this quest was automated processing of the syntactic structure of sentences, and their semantic components. Artificial neural networks was chosen as the tool to perform the research with, and as such part of the goal became research on connectionist methods. A side-goal of interest was to look into the possibility of using insight into neural networks to gain deeper understanding of how the human brain processes information, particularly language. This area was not explicitly focussed on during the research. The methodology selected for achieving the goals was to design and implement a framework for developing neural network models, and further to implement NLP and NLU systems within this framework. The systems selected to explore and implement were: a parser for handling the syntactic structure and a symbol grounding system for dealing with the semantic component. A third system was also implemented for investigation into an evolutionary-based communication model on the development of a shared vocabulary between autonomous agents. All implementations were based on recent research and results by others.</p>

<p>The emergence of complex data objects that must to be indexed and accessed in databases has created a need for access methods that are both dynamic and efficient. Lately, metric tree structures have become a popular way of handling this because of the advantages they have compared to traditional methods based on spatial indexing. The most common way to handle indexing is to build tree structures and then prune out branches of the trees during search, and for a dynamic indexing structure it is important that these trees stay balanced in order to keep the worst case search time as low as possible. Normally, this is done based on complex criteria and reshuffling operations. Another way to handle balancing is General Balanced Trees (GBT), proposed by Arne Andersson (Journal of Algorithms 30, 1999), which uses simple, global criteria for rebalancing binary search trees by using total and partial rebuilding. This thesis explores if it is possible to apply this to metric tree structures, and especially two static metric tree structures called the Vantage Point Tree and the Multiple Vantage Point Tree. It discusses how to best make these into dynamic tree structures and how to apply balancing by using GBT paradigms on them. The results of the performance of the new tree structures are analyzed, and the results are compared against already existing structures. The results shows that this works for balancing the trees, and that the structures perform reasonably well compared to already existing structures.</p>

<p>Hovedfokus i denne hovedfagsoppgaven er å gi en oversiktlig og lettfattelig innføring i data og kommunikasjonsikkerhet. Det er lagt vekt på å holde oppgaven på et såpass lavt teknisk og matematisk nivå at den vil være mulig å forstå for personer uten store datakunnskaper. Oppgaven er organisert på den måten at den starter med en grunnleggende innføring i kryptografi. Dette er nødvendig for å forstå resten av oppgaven. Deretter forklares og vises de mest utbredte sikkerhetsmekanismene innen data og kommunikasjonsikkerhet. Etter det tar jeg for meg en del spesifikke applikasjoner som brukes mye, og hva som kan gjøres for å sikre kommunikasjonen ved å ta i bruk disse. Til slutt i den teoretiske delen går jeg gjennom andre kommunikasjonsmetoder enn ethernet, som datamaskiner som oftest bruker, og hvilke sikkerhetsmekanismer som ligger innebygd i disse samt hva vi som brukere kan gjøre for å øke sikkerheten.For å gjøre sikkerhet mer tilgjengelig for vanlige brukere har jeg i den praktiske delen av oppgaven valgt å gi detaljerte beskrivelser på oppsett av tre vanlige sikkerhetsmekanismer. De tre jeg har valgt å forklare er IPSec, SSL og digitale signaturer. Grunnen til at valget falt på disse er at de på en måte representerer hvert sitt aktuelle felt innen sikkerhet. IPSec benyttes når en vil ha total sikkerhet i kommunikasjonen mellom maskiner, SSL benyttes når en bare vil ha sikkerhet på informasjonsutveksling mellom utvalgte applikasjoner og digitale signaturer tar for seg integriteten til informasjon som sendes over usikre nettverk. Figurene og beskrivelsene vil gjøre de som leser denne oppgaven i stand til å sette dette opp selv på sine egne datamaskiner.</p>

<p>Målet med denne oppgaven er å se om en automatisk kan organisere kunnskapsobjekter tilrettelagt for et tredimensjonalt navigerbart konseptkart. Forutsetningen for å gjøre dette mulig er at kunnskapen er fremstilt i enheter, kalt læringsobjekter. Et læringsobjekt består av en eller flere kunnskapsobjekter knyttet sammen med ett eller flere læringsmål, og ulike læringsaktiviteter. Et kunnskapsobjekt er bygd opp av en eller flere ressurser. Disse ressursene kan være tekst, lyd, bilde, video osv. En ser for seg at kunnskapsobjektene befinner seg i samlinger, repositories. Kunnskapsobjektene skal kunne utvikles av både faglig veileder og lærende, men hovedsakelig tenker en at de skal produseres av profesjonelle aktører. Her er det snakk om en produksjonslinje. Den profesjonelle aktøren står for produksjon og presentasjon av objektene, mens faglig veileder sørger for innhold og pedagogisk tilrettelegging. Til hvert kunnskapsobjekt er det knyttet en tekstlig beskrivelse som danner grunnlag for vektorisering. Det er denne vektoriseringen som gjør det mulig å indeksere kunnskapsobjektene, samt sammenligne dem. Sammenligningen av de ulike objektene danner grunnlag for klyngeanalyse. Klyngeanalysen vil organisere like objekter i grupper slik at hver gruppe deler felles egenskaper, dvs. har en stor grad av likhet. Med denne grupperingen kan man representere objektene visuelt, for eksempel i en tredimensjonal graf. Som en del av denne oppgaven er det utviklet to prototyper for klyngeanalyse. I den ene benyttes det K-means-algoritme, mens i den andre benyttes en agglomerativ hierarkisk algoritme. Dataen fra disse analysene er tenkt brukt i en tredimensjonal representasjon. Prototypen for K-means har en todimensjonal framstilling slik at man får et visst innblikk i hva en visuell framstilling av objektene innebærer. En vil blant annet se av testene at K-means med brukervalgte initielle klyngerepresentanter gir det beste resultatet for klyngeanalysen, og at de tekstlige beskrivelsene av kunnskapsobjektene bør være av størrelse som en vanlig A4-side.</p>

<p>Lokasjon som kontekstinformasjon blir benyttet stadig mer. Den har vist sin nytteverdi gjennom den mengde av teknologier og applikasjoner, som baserer seg på denne informasjonen. Denne typen applikasjoner er ofte brukersentrert, og gir økt funksjonalitet til en bruker. Presentasjon av en brukers lokasjon, varierer ut fra forskjellige behov og formål. Fordelene og nytteverdien denne informasjonen gir, er i de fleste tilfeller åpenbar. Arbeidet i denne oppgaven ser på hvordan kontekst kan benyttes for å gi assistanse til brukere, med fokus på besøkende og ansatte ved ac{NTNU}, i textit{acl{DIK}}. Hvordan brukermodeller kan benyttes for å gi økt funksjonalitet for brukere av systemet blir utforsket, og et løsningsforslag for hvordan dette kan gjøres blir presentert. Brukermodellene gir et forslag til hvordan informasjon kan innhentes og presenteres for brukere, ut fra hvilke interesser de har. Arbeidet har basert seg på agentrammeverket ac{JADE}, og design av systemet blir gjort ved å følge en ny metode for utvikling av multi-agentsystem. Design av et system blir presentert, hvor alle funksjoner i systemet er basert på agenter, og interaksjonen mellom disse. Arbeidet avsluttet med en prototyp av det designede systemet, og en demonstrasjon av systemet viser hvordan det kan benyttes.</p>

<p>Evolutionary algorithms (EAs) are a class of population-based stochastic search algorithms which have proven themselves to be powerful tools in optimization problems where the search space is complex, contains many local optima, and is so large that an exhaustive search is not possible. An application area where EAs have great potential is in the design of electronic circuits. However, for this type of task such a large representation is typically required for each of the proposed solutions that using an EA approach is not feasible because of the immense computational power this would require. This limitation of EAs is known as the scalability problem: EAs perform well when dealing with problems requiring a small solution representation, but when the required size for these representations increases the EAs quickly become too computationally expensive to be useful. Numerous approaches for dealing with the scalability problem have been proposed. One of the more promising approaches is inspired by the way nature copes with scaling: the process of an organism growing from a single fertilized cell and into a multi-cellular being, called development. By adapting some of the mechanisms of development to a computer program, the EA can evolve a relatively small genome which when developed i.e. decompressed, using this program will represent a solution. There are, however, some problems regarding this approach. One issue is that biological development is such a complex process that implementing it in all its detail is neither feasible nor desired, meaning a decision regarding which mechanisms to implement and which ones to leave out must be made. Another issue is the increased difficulty to evolve a good solution. This occurs because EAs depend on a gradual refinement of the solution to be effective, but with this approach a small change in the genome may lead to a large change in the corresponding solution. This is because in this approach there is no longer a direct correspondence between the genotype space and the solution space, so that what is adjacent in the genotype space may be far apart in the solution space. This means that even though gradual refinement is achieved in genotype space, the changes in the corresponding solution space may appear to be more or less random A novel artificial development system, designed and implemented from scratch, is presented in this thesis. A novel system was built because, although a number of other such system already have been implemented, they are all in the experimental stage, and this system is though to be a useful supplement to the existing ones, providing more material to base the understanding of what may be useful in an artificial development system on. An explorative approach was taken where the implemented system was put through a number of tests to investigate its capabilities. First the systems ability to develop a varied set of different shapes was investigated. Secondly, four parameters were tested for their effect on the system's ability to develop good solutions: the initial number of neighbours, the number of chemical types used (both part of a precondition), the number of cell types available to the system, and the degree of symmetry in the target shapes. The experiments performed showed that the system is able to develop a number of shapes. For the four investigated parameters, indications were found that each has a profound effect on the systems ability to develop a given target.</p>

<p>The Semantic Web is an emerging framework for data reuse and sharing. By giving data clear semantics it allows for machine processing of this information. The Semantic Web technologies range from simple meta data to domain models using the Web Ontology Languge (OWL). Much of the semantics of OWL stems from the Knowledge Representation field of Description Logics. Case-Based Reasoning (CBR) uses specific knowledge in the form of cases to solve problems. The Creek system is a Knowledge-Intensive approach to CBR that combines specific knowledge with general domain knowledge. Part of this work is to define a OWL vocabulary for Creek. This will be concepts used to describe case-bases and domain models, and how these concepts are related to each other. Using this vocabulary, a knowledge model from a Creek system can be described in OWL and shared with others on the Semantic Web. We also examines how domain ontologies can be reused and imported into a Creek knowledge model. We propose a design for Creek to operate in the context of the Semantic Web and its distributed knowledge. Part of the design will be tested by implementation.</p>