Thèses sur le sujet « Literature based discovery – methods »
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Fleig, John David. « Citationally Enhanced Semantic Literature Based Discovery ». Diss., NSUWorks, 2019. https://nsuworks.nova.edu/gscis_etd/1082.
Texte intégralRadovanovic, Aleksandar. « Concept Based Knowledge Discovery from Biomedical Literature ». Thesis, Online access, 2009. http://etd.uwc.ac.za/usrfiles/modules/etd/docs/etd_gen8Srv25Nme4_9861_1272229462.pdf.
Texte intégralAamot, Elias. « Literature-based knowledge discovery in climate science ». Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for datateknikk og informasjonsvitenskap, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-27047.
Texte intégralYildiz, Meliha Yetisgen. « Using statistical and knowledge-based approaches for literature-based discovery / ». Thesis, Connect to this title online ; UW restricted, 2007. http://hdl.handle.net/1773/7178.
Texte intégralCameron, Delroy Huborn. « A Context-Driven Subgraph Model for Literature-Based Discovery ». Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1417034001.
Texte intégralHenry, Sam. « Indirect Relatedness, Evaluation, and Visualization for Literature Based Discovery ». VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5855.
Texte intégralLi, Lizhi. « Graphic Network based Methods in Discovering TFBS Motifs ». The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1325276730.
Texte intégralSeki, Kazuhiro. « Literature-based discovery finding implicit associations between genes and diseases / ». [Bloomington, Ind.] : Indiana University, 2006. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3232584.
Texte intégral"Title from dissertation home page (viewed July 10, 2007)." Source: Dissertation Abstracts International, Volume: 67-08, Section: A, page: 2796. Adviser: Javed Mostafa.
Yu, Zhiguo. « Cooperative Semantic Information Processing for Literature-Based Biomedical Knowledge Discovery ». UKnowledge, 2013. http://uknowledge.uky.edu/ece_etds/33.
Texte intégralAlvarsson, Jonathan. « Ligand-based Methods for Data Management and Modelling ». Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-248964.
Texte intégralDharmavaram, Sirisha. « Mining Biomedical Data for Hidden Relationship Discovery ». Thesis, University of North Texas, 2019. https://digital.library.unt.edu/ark:/67531/metadc1538709/.
Texte intégralMartin, Garcia German [Verfasser]. « Saliency Methods for Object Discovery Based on Image and Depth Segmentation / German Martin Garcia ». Bonn : Universitäts- und Landesbibliothek Bonn, 2016. http://d-nb.info/1113688335/34.
Texte intégralChang, Max W. « Computational structure-based methods to anticipate HIV drug resistance evolution and accelerate inhibitor discovery ». Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3315120.
Texte intégralTitle from first page of PDF file (viewed August 4, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 128-139).
Jacobsson, Micael. « Structure-Based Virtual Screening : New Methods and Applications in Infectious Diseases ». Doctoral thesis, Uppsala universitet, Avdelningen för organisk farmaceutisk kemi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9302.
Texte intégralRUI, MARTA. « TOWARDS THE DISCOVERY OF NOVEL SIGMA RECEPTOR MODULATORS : ORGANOLITHIUM-METHODS BASED SYNTHESIS AND BIOLOGICAL EVALUATIONS ». Doctoral thesis, Università degli studi di Pavia, 2017. http://hdl.handle.net/11571/1203334.
Texte intégralSpringborg, Claus. « Art-based Methods in Management Education ». Thesis, Cranfield University, 2014. http://dspace.lib.cranfield.ac.uk/handle/1826/9212.
Texte intégralESRC (Economic and Social Research Council)
Tang, Man. « Statistical methods for variant discovery and functional genomic analysis using next-generation sequencing data ». Diss., Virginia Tech, 2020. http://hdl.handle.net/10919/104039.
Texte intégralDoctor of Philosophy
The development of high-throughput next-generation sequencing (NGS) techniques produces massive amount of data and bring out innovations in biology and medicine. A greater concentration is needed in developing novel, powerful, and efficient tools for NGS data analysis. In this dissertation, we mainly focus on three problems closely related to NGS and its applications: (1) how to improve variant calling accuracy, (2) how to model transcription factor (TF) binding patterns, and (3) how to quantify of the contribution of TF binding on gene expression. We develop novel statistical methods to identify sequence variants, find TF binding patterns, and explore the relationship between TF binding and gene expressions. We expect our findings will be helpful in promoting a better understanding of disease causality and facilitating the design of personalized treatments.
Beaudry, Francis. « Development of analytical methods based on liquid chromatography and mass spectrometry techniques to support drug discovery and development programmes ». Thesis, Anglia Ruskin University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436459.
Texte intégralLindström, Johan. « Teaching Literature : A Qualitative Study Based On Teachers’ Experiences, Thoughts and Ideas ». Thesis, Linnéuniversitetet, Institutionen för språk (SPR), 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-52460.
Texte intégralLane, Taylor S., Julie Armin et Judith S. Gordon. « Online Recruitment Methods for Web-Based and Mobile Health Studies : A Review of the Literature ». JMIR, 2015. http://hdl.handle.net/10150/621267.
Texte intégralBackground: Internet and mobile health (mHealth) apps hold promise for expanding the reach of evidence-based health interventions. Research in this area is rapidly expanding. However, these studies may experience problems with recruitment and retention. Web-based and mHealth studies are in need of a wide-reaching and low-cost method of recruitment that will also effectively retain participants for the duration of the study. Online recruitment may be a low-cost and wide-reaching tool in comparison to traditional recruitment methods, although empirical evidence is limited. Objective: This study aims to review the literature on online recruitment for, and retention in, mHealth studies. Methods: We conducted a review of the literature of studies examining online recruitment methods as a viable means of obtaining mHealth research participants. The data sources used were PubMed, CINAHL, EbscoHost, PyscINFO, and MEDLINE. Studies reporting at least one method of online recruitment were included. A narrative approach enabled the authors to discuss the variability in recruitment results, as well as in recruitment duration and study design. Results: From 550 initial publications, 12 studies were included in this review. The studies reported multiple uses and outcomes for online recruitment methods. Web-based recruitment was the only type of recruitment used in 67% (8/12) of the studies. Online recruitment was used for studies with a variety of health domains: smoking cessation (58%; 7/12) and mental health (17%; 2/12) being the most common. Recruitment duration lasted under a year in 67% (8/12) of the studies, with an average of 5 months spent on recruiting. In those studies that spent over a year (33%; 4/12), an average of 17 months was spent on recruiting. A little less than half (42%; 5/12) of the studies found Facebook ads or newsfeed posts to be an effective method of recruitment, a quarter (25%; 3/12) of the studies found Google ads to be the most effective way to reach participants, and one study showed better outcomes with traditional (eg in-person) methods of recruitment. Only one study recorded retention rates in their results, and half (50%; 6/12) of the studies recorded survey completion rates. Conclusions: Although online methods of recruitment may be promising in experimental research, more empirical evidence is needed to make specific recommendations. Several barriers to using online recruitment were identified, including participant retention. These unique challenges of virtual interventions can affect the generalizability and validity of findings from Web-based and mHealth studies. There is a need for additional research to evaluate the effectiveness of online recruitment methods and participant retention in experimental mHealth studies.
Das, Neves Fernando Adrian. « Stepping Stones and Pathways:Improving Retrieval by Chains of Relationships between Documents ». Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/29419.
Texte intégralPh. D.
Sarafraz, Farzaneh. « Finding conflicting statements in the biomedical literature ». Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/finding-conflicting-statements-in-the-biomedical-literature(963e490a-eeea-4f4c-864d-fb318899beed).html.
Texte intégralAl-Fadda, Hind Abdulaziz. « Literature synthesis and inventory of reading methods used by Kansas middle schools for Content-Based Reading Approaches (COBRAS) / ». Search for this dissertation online, 2004. http://wwwlib.umi.com/cr/ksu/main.
Texte intégralSpringborg, Claus. « Arts-based methods for facilitating meta-level learning in management education : Making and expressing refined perceptual distinctions ». Thesis, Cranfield University, 2011. http://dspace.lib.cranfield.ac.uk/handle/1826/6972.
Texte intégralChrysostomou, Charalambos. « Characterisation and classification of protein sequences by using enhanced amino acid indices and signal processing-based methods ». Thesis, De Montfort University, 2013. http://hdl.handle.net/2086/9895.
Texte intégralSillner, Nina [Verfasser], Philippe [Akademischer Betreuer] Schmitt-Kopplin, Philippe [Gutachter] Schmitt-Kopplin et Dirk [Gutachter] Haller. « Optimization of liquid chromatography-mass spectrometry-based methods for the discovery of microbial and nutritional metabolites / Nina Sillner ; Gutachter : Philippe Schmitt-Kopplin, Dirk Haller ; Betreuer : Philippe Schmitt-Kopplin ». München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/1208831747/34.
Texte intégralBaker, Simon. « Semantic text classification for cancer text mining ». Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275838.
Texte intégralBalachandran, Appu, et Tunhult Dennis Karlsson. « A Conceptual Study on Model-Based Systems Engineering and Data Driven Methods in the Context of Complex Products and Systems ». Thesis, Linköpings universitet, Projekt, innovationer och entreprenörskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-170305.
Texte intégralMa, Sihui. « Discovery and dissemination of new knowledge in food science : Analytical methods for quantification of polyphenols and amino acids in fruits and the use of mobile phone-based instructional technology in food science education ». Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/100997.
Texte intégralDoctor of Philosophy
Saud, Haris, et Ruth Chen. « The Effect of Competency-Based Education on Medical and Nursing Students' Academic Performance, Technical Skill Development, and Overall Satisfaction and Preparedness for Future Practice : An Integrative Literature Review ». Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/ijhse/vol5/iss1/3.
Texte intégralAdusei-Owusu, James. « Research projects ». Thesis, Rhodes University, 2001. http://hdl.handle.net/10962/d1003624.
Texte intégralHosseini, S. (Seyedrebvar). « Data selection for cross-project defect prediction ». Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526224480.
Texte intégralTiivistelmä Tausta: Tämä tutkimus edistää projektienvälisten virheiden ennustamisen nykytilan ymmärtämistä (CPDP) tutkimalla aihetta teemoissa, keskittyen erityisesti tiedollisiin lähestymistapoihin ja hakuperusteisen harjoitusdatan valintaan esittelemällä datan valintamenetelmiä ja tutkimalla niiden vaikutuksia. Tämän työn empiirinen todistusaineisto on koottu muodollisella systemaattisella kirjallisuuskatsauksella ja avoimen lähdekoodin projekteissa tehdyillä kokeilla. Tavoite: Pyrimme ymmärtämään ja tiivistämään tavan, jolla erilaisia datan käsittelyn lähestymistapoja käytetään CPDP:ssa sekä niiden potentiaalisia vaikutuksia suorituskykyyn. Lisäksi, tavoitteenamme on hyödyntää hakuperusteisia menetelmiä muodostamaan kehittyviä harjoitusdata-settejä suodattamaan epäolennaisia esiintymiä muista projekteista ennen koulutusta. Menetelmä: CPDP:n nykytilan kirjallisuuskatsauksen jälkeen tehtyjen tutkimusten avulla ehdotamme hakuperusteista menetelmää, jota kutsutaan geneettisen esiintymän valinnaksi (GIS). Todistamme alustavat havaintomme suorittamalla seuraavan tutkimuksen suurella joukolla datasettejä, joilla on useita ominaisuuksia. Jalostamme suunnittelupäätöksiämme käyttäen tutkivaa tutkimusta. Lopuksi, tutkimme vallitsevaa meta-oppimisen lähestymistapaa ja tarjoamme näkemyksiä sen suunnitteluun ja ehdotamme vaihtoehtoista, toistuvaa datan valintamenetelmää. Tulokset: Kirjallisuuskatsaus paljastaa CPDP:n heikomman suorituskyvyn verrattuna projektinsisäisten virheiden ennustamisen (WPDP) malleihin ja tarjoaa joukon primaaritutkimuksia, joita voidaan käyttää perustana myöhemmälle tutkimukselle. Ehdottamamme datan valintamenetelmät puoltavat hakuperusteisten menetelmiä niiden paremman tehokkuuden ja suorituskyvyn vuoksi. Tunnistimme potentiaalisia tehokuuteen vaikuttavia tekijöitä tutkivien tutkimusten avulla ja ehdotimme metodeja parempien CPDP mallien luomiseksi. Johtopäätökset: Viime vuosikymmenten aikana kirjallisuudessa esitellyt lukuisat menetelmät ovat edistäneet alaa ja hankittu tieto ja työkalut soveltuvat monille samanlaisille alueille ja voivat toimia myös osana akateemisia opetussuunnitelmia. Tutkimuksen tulevat linjaukset voivat sisältää validointiin paremmin soveltuvan datan haun, paremmat ominaisuuksien valintatekniikat, hakuperusteisten mallien parametrien hienosäädön, oppijoiden hyper-parametrien hienosäädön, tutkimuksen useiden optimoinnin lähteiden vaikutuksista (oppija, esiintymät, ominaisuudet) ja luokan epätasapaino-ongelman vaikutuksesta
Durán, Alcaide Ángel. « Development of high-performance algorithms for a new generation of versatile molecular descriptors. The Pentacle software ». Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7201.
Texte intégralEl trabajo que se presenta en esta tesis se ha centrado en el desarrollo de algoritmos de altas prestaciones para la obtención de una nueva generación de descriptores moleculares, con numerosas ventajas con respecto a sus predecesores, adecuados para diversas aplicaciones en el área del diseño de fármacos, y en su implementación en un programa científico de calidad comercial (Pentacle). Inicialmente se desarrolló un nuevo algoritmo de discretización de campos de interacción molecular (AMANDA) que permite extraer eficientemente las regiones de máximo interés. Este algoritmo fue incorporado en una nueva generación de descriptores moleculares independientes del alineamiento, denominados GRIND-2. La rapidez y eficiencia del nuevo algoritmo permitieron aplicar estos descriptores en cribados virtuales. Por último, se puso a punto un nuevo algoritmo de codificación independiente de alineamiento (CLACC) que permite obtener modelos cuantitativos de relación estructura-actividad con mejor capacidad predictiva y mucho más fáciles de interpretar que los obtenidos con otros métodos.
Achuo, George. « Partner satisfaction and renewal likelihood in consumer supported agriculture (CSA) : a case study of The Equiterre CSA network ». Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19555.
Texte intégralFujdiak, Radek. « Analýza a optimalizace datové komunikace pro telemetrické systémy v energetice ». Doctoral thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2017. http://www.nusl.cz/ntk/nusl-358408.
Texte intégralGuo, Tai-Ying, et 郭岱茵. « Impact Mining for Supporting Literature-based Discovery ». Thesis, 2012. http://ndltd.ncl.edu.tw/handle/03411110908673228406.
Texte intégral國立臺灣大學
資訊管理學研究所
100
Scientific literature has growth rapidly in the past century, and a great deal of knowledge can support medical researchers to keep up with up-to-date information. This large volume of data is difficult to discover hidden relationships. To overcome this problem, Swanson proposed a method called literature-based discovery in 1986 to support researchers an effective way to uncovering new, potentially meaningful relationships. After Swanson proposed this method, other researchers also try to improve the result from literature-base discovery or develop new method to improve. Researchers could employ literature-based discovery to support them reduce the time of discovering hidden relationships. But literature-based discovery method could not provide more information such as fish oil and blood viscosity is a suppressing relationship because fish oil can decrease blood viscosity. The kind of relationship we defined as impact relationship. Therefore, this study proposed a LBD (Impact) technique which is based on the concept of literature-based discovery and this technique can extract impact relationship to support researchers easier to analyze large volume of data. First, we apply literature-based discovery to retrieve related medical concepts. Subsequently, we use our proposed technique to extract impact relationship then order medical concepts in an appropriate way. We construct two scenarios to evaluate our proposed LBD (Impact) technique, disease-chemicals and drugs scenario and drug-chemicals and drugs scenario. In disease-chemicals and drugs scenario, researchers usually focus on which drug can cure disease. And our proposed technique can rank drugs that can cure disease at higher rank. In the other scenario, drug-chemicals and drugs scenario, although the experiment result is not better than disease-chemicals and drugs scenario, we still can provide a better result to researchers. For researchers, they usually pay more attention on top 100 or 300. In this study, our proposed technique can provide a better result for researchers.
Lee, Kun-Pu, et 李坤樸. « Literature-based Discovery for Drug Repurposing : A Path-importance-based Approach ». Thesis, 2017. http://ndltd.ncl.edu.tw/handle/14698997967264068188.
Texte intégral國立臺灣大學
資訊管理學研究所
105
Drug development is costly and time-consuming. According to United States Food and Drug Administration (FDA), drug development consists of five stages, including drug discovery, clinical test, FDA review, etc. However, once one of the stages fails, the investment on candidate drug seldom returns. As a result, to overcome the challenges of drug development, researchers start to explore alternative methods for drug development. Drug repurposing discovery, finding new indications for existing drugs, has been proposed to help reduce cost and time needed for drug development. Swanson (1986) originally proposed a drug repurposing approach that analyzes biomedical literatures to uncover implicit relationships. Previous studies following Swanson’s ABC model encountered several limitations. Therefore, in this research, we propose a path-importance-based approach, which constructs a concept network based on semantic predication, trains a classification model to determine the importance of paths that connecting a focal drug and a candidate disease, and finally ranks candidate diseases according to the importance of paths identified by the path importance classification model. In our systematic evaluation experiments, we prove that our path importance classification model achieves a satisfactory effectiveness, and that adopting the concept of path importance into the ranking of candidate drugs for drug repurposing outperforms the traditional method.
Liu, Yu-Tang, et 劉育唐. « A Study of Swarm Intelligence Based DNA Motif Discovery Methods ». Thesis, 2011. http://ndltd.ncl.edu.tw/handle/62406660580506409854.
Texte intégral國立高雄應用科技大學
電子工程系
99
The identification of transcription factor binding sites (TFBSs) is important for understanding the genetic regulatory system, but weak conservation of TFBSs poses a challenge in computational biology. In this thesis, a new method based on Ant Colony Optimization (ACO) and Expectation Maximization (EM) algorithm is proposed to discover DNA motifs (collections of TFBSs) in a set of bio-sequences. ACO is a well-received swarm intelligence algorithm, which is used to build candidate motifs in this method to search for putative binding sites amongst the given sequences. The EM algorithm is then applied to maximize the likelihood of a motif model being constructed from the corresponding binding sites. In ACO, each artificial ant mimics the foraging behavior of social insects to construct a possible motif by sensing the pheromones laid on each nucleotide. Due to stability issues with metaheuristic approaches, we incorporate the EM algorithm in our method to improve the reliability of binding site predictions. In a final step, a statistically-based procedure is applied to refine the predictions for compliance with real biological conditions. Experiments conducted on real test datasets indicate that the proposed method identifies binding sites with higher accuracy and reliability than two other motif discovery tools, namely GAME and GALF.
Chen, Yun-Jing, et 陳昀靖. « Literature-based Discovery for Drug Repositioning : A Predicate-Pattern-Importance Ranking Approach ». Thesis, 2019. http://ndltd.ncl.edu.tw/handle/wnzcq9.
Texte intégral國立臺灣大學
資訊管理學研究所
107
Drug development is extremely costly and risky, so researchers are looking for alternative approaches. There’s a new approach: Drug Repurposing, using existing drugs approved by FDA to find new indications. Compared with the development of new drugs, existing drugs have more complete clinical drug information and human safety data. It not only can shorten development time but also reduce the risks on R&D. In 1986, Swanson proposed an approach using information retrieval and text mining techniques to construct a biomedical network composed of links between biomedical concepts from biomedical literatures. Through analyzing this network, drug repurposing can be achieved. Many researchers have followed this approach. Previous studies (Lee, 2017) proposed a path-importance-based approach. We follow this approach. In our research, we use machine learning techniques to convert biomedical entities and relations into representative biomedical vectors, discriminate whether a path is important or not and decide the candidate diseases given a focal drug. The empirical results show that the representative biomedical vectors can significantly improve the path-importance-based classification, which in turn can support effective drug repurposing.
Krieger, Ralph [Verfasser]. « Efficient density based methods for knowledge discovery in databases / vorgelegt von Ralph Krieger ». 2008. http://d-nb.info/990401383/34.
Texte intégralFrattaruolo, Luca, Sebastiano Andò et Anna Rita Cappello. « Genomics based discovery and anticancer activity assessment of new thioviridamide-like molecules produced by actinobacteria ». Thesis, 2019. http://hdl.handle.net/10955/1768.
Texte intégralFin dalla scoperta della penicillina da parte di Alexander Fleming nel 1928, i prodotti naturali microbici hanno rappresentato una risorsa essenziale per lo sviluppo di nuovi agenti farmacologici. All’interno dell’immenso panorama di microorganismi che popolano gli ecosistemi terrestri e marini, i batteri appartenenti al phylum Actinobacteria rappresentano la principale fonte di molecole naturali bioattive. Il metabolismo secondario di questi mircroorganismi, infatti, è complesso e molto variabile, ed è responsabile della produzione di molecole molto diverse dal punto di vista chimico, biosintetico e dell’attività biologica. Una classe di metaboliti secondari relativamente recente ma in rapida espansione, è rappresentata dai peptidi sintetizzati a livello ribosomiale e modificati a livello post-traduzionale (RiPPs). Questi prodotti naturali peptidici sono dotati di diverse attività biologiche e un enorme potenziale farmacologico, con uno spettro di attività che include, tra le tante, quella antibatterica, antitumorale, ipolipidemizzante e immunomodulatrice. L’evidenza del potenziale biologico di queste molecole ha, pertanto, spinto l’interesse della ricerca biotecnologica e farmaceutica a concentrarsi su questa classe di metaboliti secondari. L’attenzione è rivolta, in particolare, all’identificazione di nuovi ceppi batterici produttori di RiPPs bioattivi e alla caratterizzazione dei pathway biosintetici, allo scopo di comprendere meglio gli aspetti biochimici alla base della loro biosintesi. In questo scenario si colloca la thioviridamide, RiPP biosintetizzato da Streptomyces olivoviridis NA005001 e caratterizzato da una potente attività antiproliferativa e pro-apoptotica nei confronti di diverse linee cellulari tumorali. Questo composto peptidico, unico nel suo genere, presenta un gruppo 2-idrossi-2-metil-4-oxopentanoile all’estremità N-terminale, un residuo di β-idrossi-N1,N3-dimetilistidinio (hdmHis), un residuo di S-(2-aminovinil)-cisteina (AviCys) che fa parte di un macro-ciclo e cinque gruppi tioammidici che sostituiscono i gruppi ammidici nello scheletro peptidico. Recentemente, il cluster genico responsabile della biosintesi della thioviridamide è stato identificato, dimostrando l'origine ribosomiale di questa molecola, ma i processi biosintetici alla base della sua produzione non sono ancora completamente noti. La promettente attività antitumorale della thioviridamide, così come la sua peculiare struttura chimica e l'interessante pathway biosintetico, rendono questo composto estremamente interessante agli occhi della ricerca. La prima parte di questo lavoro di tesi ha avuto l’obbiettivo di identificare, mediante un approccio genomico, nuovi prodotti naturali, analoghi della thioviridamide, biosintetizzati da Actinobacteria, e di effettuarne la caratterizzazione chimico-funzionale, allo scopo di valutarne il potenziale antitumorale. Studi bioinformatici, basati sull’utilizzo di tools per l’analisi di omologie di sequenza, hanno permesso di individuare, all’interno del vasto panorama di batteri dal genoma noto, microorganismi contenenti nel proprio genoma cluster genici simili a quello responsabile della biosintesi della thioviridamide. I cluster genici identificati in questi microorganismi sono risultati essere leggermente difformi da quello presente in S. olivoviridis, con differenze sia a livello del peptide precursore e sia a livello dei sistemi enzimatici di maturazione che lo convertono in un RiPP maturo. Tali microorganismi, pertanto, appaiono essere potenziali produttori di molecole strutturalmente analoghe alla thioviridamide, con caratteristiche chimiche e biologiche sconosciute alla comunità scientifica. Tre dei diversi ceppi batterici identificati si sono rivelati capaci di produrre, in determinate condizioni sperimentali, molecole analoghe alla thioviridamide: - Thiostreptamide S4, prodotto da Streptomyces sp. NRRL S-4 - Thiostreptamide S87, prodotto da Streptomyces sp. NRRL S-87 - Thioalbamide, prodotto da Amycolatopsis Alba DSM 44262 La correlazione tra i cluster genici e i nuovi prodotti naturali identificati è stata confermata mediante due diversi approcci biologico-molecolari: - la delezione del cluster genico nel ceppo batterico produttore, che ha portato alla generazione di mutanti incapaci di produrre i composti identificati. - l’espressione eterologa del cluster genico, che ha portato alla produzione dei composti precedentemente identificati in un microorganismo ospite, Streptomyces coelicolor M1146. I risultati ottenuti hanno permesso di stabilire che la thioviridamide non è una molecola unica nel suo genere, ma fa parte di una famiglia di composti, identificati in questo studio, a cui è stato dato il nome di thioviridamide-like molecules (TLMs). Uno scale-up dei processi fermentativi ha permesso di purificare i tre nuovi prodotti naturali in quantità sufficenti per la loro caratterizzazione chimica, effettuata mediante spettrometria di massa e di risonanza magnetica nucleare (NMR). Questo studi hanno confermato la diversità. chimica dei TLMs, dal punto di vista della sequenza aminoacidica, sebbene sono risultate essere conservate alcune caratteristiche peculiari della thioviridamide, quali la presenza di un macrociclo, una carica elettrica positiva conferita da un residuo di dimetil-istidinio e la presenza di legami tioammidici nello scheletro peptidico. Inoltre, dai risultati ottenuti è emerso che i TLMs sono caratterizzati dalla presenza all’estremità N-terminale di un gruppo piruvile o lattile, e il gruppo 2-idrossi-2-metil-4-oxopentanoile, caratterizzante l’estremità N-terminale della thioviridamide, è risultato essere un artefatto, generato da una reazione di condensazione aldolica tra il gruppo piruvile della molecola naturale e l’acetone utilizzato come solvente nel processo di purificazione. La thioalbamide, il prodotto naturale purificato in maggiore quantità, è stato quindi oggetto di indagini biologiche al fine di valutarne l’attività antiproliferativa e il potenziale antitumorale. I risultati ottenuti hanno evidenziato un’intensa attività antiproliferativa nei confronti di una vasta gamma di linee cellulari tumorali. Questi effetti sono risultati essere altamente selettivi per le cellule tumorali, in quanto il composto ha mostrato scarsa attività in un modello cellulare non tumorale. La seconda parte di questo lavoro di tesi ha avuto l’obbiettivo di investigare a fondo sui meccanismi molecolari alla base dell’attività antitumorale della thioalbamide in diversi modelli in vitro di carcinoma mammario, il tumore maggiormente diagnosticato tra le donne nel mondo. In questa parte del lavoro è stato utilizzato un approccio biochimico-metabolico, per valutare per la prima volta, gli effetti cellulari indotti dalla thioalbamide in linee cellulari tumorali che riflettono la diversità biologica dei diversi sottotipi di carcinoma mammario. Nei diversi modelli utilizzati, la molecola non ha mostrato significative differenze di attività antiproliferativa, dimostrando che il suo potenziale antitumorale è indipendente dal profilo recettoriale tumorale. In particolare, la thioalbamide ha dimostrato possedere abilità di indurre cambiamenti morfologici nelle cellule trattate, blocco del ciclo cellulare a livello del checkpoint G1/S e morte cellulare mediata da meccanismi apoptotici. L’apoptosi è stata confermata con diversi approcci sperimentali atti a monitorare diversi eventi chiave del processo di morte programmata, quali la frammentazione del DNA, la perdita del potenziale di membrana mitocondriale e l’esposizione della fosfatidilserina sul foglietto esterno della membrana cellulare. In aggiunta, gli eventi di morte cellulare sono risultati essere il frutto dell’innesco dei pathway apoptotici estrinseco ed intrinseco, mediati rispettivamente dal attivazione proteolitica delle caspasi 8 e 9. Lo studio delle alterazioni biochimiche indotte dalla thioalbamide è proseguito, facendo emergere la capacità del composto di derterminare nella cellula un aumento nella produzione di specie reattive dell’ossigeno (ROS), che si sono rivelate il fenomeno scatenante la morte apoptotica indotta dalla thioalbamide. L’eccessivo aumento dei livelli intracellulari di ROS indotto dal trattamento, è risultato interessare particolarmente il compartimento mitocondriale della cellula. Questa evidenza è emersa dal momento che la cellula tumorale risponde allo stress ossidativo, indotto dal composto, con un aumento selettivo dell’isoforma mitocondriale della superossido dismutasi (SOD2), enzima deputato alla neutralizzazione dell’anione superossido, principale subprodotto della respirazione cellulare. Essendo i ROS generati dal metabolismo cellulare, il loro accumulo e il conseguente stress ossidativo sono spesso associati ad alterazioni dei pathway metabolici. La riprogrammazione metabolica è una delle caratteristiche del cancro, e i tumori richiedono cataboliti per produrre ATP, mantenere un equilibrio redox e generare biomassa. A seconda della disponibilità di nutrienti, alcune cellule all’interno del tumore sono prevalentemente glicolitiche, mentre altre hanno un fenotipo dipendente dalla fosforilazione ossidativa. Pertanto, in questo lavoro, è stato valutato anche il profilo energetico delle cellule trattate con thioalbamide, e i risultati ottenuti hanno evidenziato la capacità di questo prodotto naturale di inibire la glicolisi e la fosforilazione ossidativa, i due principali pathway energetici cellulari. Il metabolismo della cellula tumorale rappresenta un potenziale target per la terapia oncologica. Infatti, è noto che le cancer stem cells (CSCs), la sottopopolazione di cellule tumorali responsabile dell’insorgenza di fenomeni di recidiva e metastatizzazione, sono caratterizzate da una elevata flessibilità metabolica. La thioalbamide, spegnendo il metabolismo energetico tumorale, si è rivelata in grado di inibire la crescita e propagazione delle CSCs, riducendo l’efficienza di formazione di mammospheres (MFE). Nel complesso, questo lavoro di dottorato ha portato alla luce nuove conoscenze sui metaboliti secondari microbici, identificando nuovi membri della classe dei RiPPs che da oggi costituiscono la famiglia delle thioviridamide-like molecules (TLMs). Inoltre, per la prima volta, sono stati studiati i meccanismi molecolari indotti da questi nuovi prodotti naturali e, dai risultati ottenuti, è emerso che l’elevato potenziale antitumorale della thioalbamide è dovuto alla sua capacità di spegnere il metabolismo energetico della cellula maligna.
Università della Calabria
« Pattern discovery for deciphering gene regulation based on evolutionary computation ». Thesis, 2010. http://library.cuhk.edu.hk/record=b6075246.
Texte intégralTF-TFBS associated sequence pattern (rule) discovery is further investigated for better deciphering protein-DNA interactions in regulation. We for the first time generalize previous exact TF-TFBS rules to approximate ones using a progressive approach. A customized algorithm is developed, outperforming MEME by over 73%. The approximate TF-TFBS rules, compared with the exact ones, have significantly more verified rules and better verification ratios. Detailed analysis on PDB cases and conservation verification on NCBI protein records illustrate that the approximate rules reveal the flexible and specific protein-DNA interactions with much greater generalized capability.
The comprehensive pattern discovery algorithms developed will be further verified, improved and extended to further deciphering transcriptionial regulation, such as inferring whole gene regulatory networks by applying TFBS and TF-TFBS patterns discovered and incorporating expression data.
Transcription Factor (TF) and Transcription Factor Binding Site (TFBS) bindings are fundamental protein-DNA interactions in transcriptional regulation. TFs and TFBSs are conserved to form patterns (motifs) due to their important roles for controlling gene expressions and finally affecting functions and appearances. Pattern discovery is thus important for deciphering gene regulation, which has tremendous impacts on the understanding of life, bio-engineering and therapeutic applications. This thesis contributes to pattern discovery involving TFBS motifs and TF-TFBS associated sequence patterns based on Evolutionary Computation (EC), especially Genetic Algorithms (GAs), which are promising for bioinformatics problems with huge and noisy search space.
Chan, Tak Ming.
Advisers: Kwong-Sak Leung; Kin-Hong Lee.
Source: Dissertation Abstracts International, Volume: 73-03, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 147-153).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstract also in Chinese.
Dragomir, Andrei. « Discovery of gene interactions in regulatory networks using genomic data mining and computational intelligence methods ». Thesis, 2006. http://nemertes.lis.upatras.gr/jspui/handle/10889/1176.
Texte intégralH έλευση ικανών υπολογιστικών εργαλείων για την μελέτη της γενομικής ακολουθίας και της ερευνητικής βιοτεχνολογίας υψηλής ανάλυσης, οδήγησε σε μια τεράστια πρόοδο στις επιστήμες ζωής. Μεταξύ των πιο σημαντικών καινοτομιών είναι η τεχνολογία μικροσυστοιχιών. H τεχνολογία αυτή επιτρέπει την ποσοτικοποίηση της έκφρασης χιλιάδων γονιδίων ταυτόχρονα, μετρώντας τον υβριδισμό από έναν ιστό ενδιαφέροντος έως σε δείγματα σε μικρό γυαλί η σε πλαστικά τσιπ. Πριν ξεκινήσουμε την έρευνα πάνω στις μικροσυστοιχίες είναι σημαντικό να θυμόμαστε ότι τα χαρακτηριστικά των δεδομένων αυτής περιλαμβάνουν αρκετό ποσό θορύβου και ένα μη τυπικό αριθμό διαστάσεων (το οποίο καθιστά δύσκολη την χρήση κλασσικών στατιστικών μεθόδων – μέγεθος δείγματος σε δωδεκάδες και μέγεθος χαρακτηριστικών σε χιλιάδες η δεκάδες η εκατοντάδες). Επομένως, ο κύριος στόχος αυτής της διδακτορικής εργασίας είναι η ανάπτυξη ικανών υπολογιστικών μεθόδων και αλγόριθμων έτσι ώστε να εξάγουν πολύτιμη βιολογική γνώση από τον συγκεκριμένο τύπο δεδομένων. Εφαρμογές της τεχνολογίας μικροσυστοιχιών σαν ένα εργαλείο για την ανάλυση έκφρασης γονιδίων ξεκινούν από την εύρεση και απόδοση λειτουργικών κατηγοριών για γονίδια άγνωστης βιολογικής λειτουργικότητας (βασισμένη στην ανάλυση των γονιδίων ήδη εδραιωμένου βιολογικού ρόλου) έως την ακριβή και πρώιμη διάγνωση διαφορετικών κακοήθων όγκων. Όμως ο κύριος στόχος της υπολογιστικής ανάλυσης της έκφρασης γονιδίων είναι η εξαγωγή ρυθμιζόμενης γνώσης στο γενετικό επίπεδο το οποίο μπορεί να χρησιμοποιηθεί ώστε να παρέχει μία ευρύτερη κατανόηση της λειτουργίας πολύπλοκων κυτταρικών συστημάτων. Σε αυτή την κατεύθυνση, το να αναδεικνύεις τις δομές ρυθμιστικών δικτύων βασισμένων στην έκφραση γονιδίων γίνεται καίριο έργο. Η διδακτορική διατριβή συνεισφέρει στο πλαίσιο για την ανακάλυψη βιολογικά λειτουργικών κατηγοριών γονιδίων βασισμένη στην συνεργία της ΙCA και της δυναμικού βασισμένου στη SOM ομαδοποίηση αλγορίθμου η οποία με ακρίβεια βρίσκει ομάδες γονιδίων που συν-ρυθμίζονται ενώ παράλληλα αναγνωρίζει ενδιαφέροντα ρυθμιστικά σήματα μέσα στα δεδομένα με τη βοήθεια της ΙCA αποδόμησης. Eπίσης, προσανατολιζόμαστε στην εύρεση του μοριακού χαρακτηρισμού διαφορετικών τύπων όγκων χρησιμοποιώντας το προφίλ της γονιδιακής έκφρασης, βασισμένο σε ένα σύνολο κατηγοριοποιητών οι οποίοι εκπαιδεύτηκαν σειριακά σε επανασταθμισμένες παραλλαγές των δεδομένων. Ο αλγόριθμος, γνωστός και σαν boosting, έχει προσαρμοστεί στις ιδιαιτερότητες των δεδομένων έκφρασης γονιδίου και εφαρμόζεται σε συνδυασμό με τα SVMs. Επιπλέον, εξετάζεται η πρωτοποριακή τεχνική της εύρεσης προβλέψιμων τιμών των οποίων οι υπογραφές είναι σημαντικές για τον χαρακτηρισμό φαινότυπου. Τελικά, η παρούσα διδακτορική διατριβή παρουσιάζει μια μέθοδο που αναπτύχθηκε για αντίστροφα μηχανικά ελεγχόμενα από γονίδια νευρωνικά δίκτυα βασισμένα σε αναδρομικά νευρωνικά δίκτυα τύπου fuzzy, τα οποία αξιοποιούν τα πλεονεκτήματα των μοντέλων τύπου fuzzy σε βάση επεξηγηματικότητας αποτελεσμάτων, και αυτών των νευρωνικών δικτύων σε βάση υπολογιστικής δύναμης και ικανότητας πρόβλεψης χρονοσειρών.
Rietze, Michel, Florian Lenk et Moritz Hesse. « Recommendations for the Selection of Methods for the Analysis of eCollaboration based on a Systematic Literature Review ». 2019. https://tud.qucosa.de/id/qucosa%3A33490.
Texte intégralGültas, Mehmet. « Development of novel Classical and Quantum Information Theory Based Methods for the Detection of Compensatory Mutations in MSAs ». Doctoral thesis, 2013. http://hdl.handle.net/11858/00-1735-0000-0022-5EB0-1.
Texte intégral« Something about Self : Moving the Creative Flow Within ». Master's thesis, 2012. http://hdl.handle.net/2286/R.I.14729.
Texte intégralDissertation/Thesis
M.F.A. Dance 2012
Dilrajh, Kamla Moonsamy. « Fasilitering van leer in kommunikatiewe T²-Afrikaanstaalonderrig ». Diss., 1998. http://hdl.handle.net/10500/18009.
Texte intégralIn die studie is daar gepoog om aan te toon waarom die ondervindingsmod~l vir taalleer die aangewese model vir effektiewe tweedetaalleer is. Die kommunikatiewe onderrigbenaderingswyse, onderhandeling in die klaskamer en die belangrikheid van die prosessillabus in tweedetaalverwerwing is bespreek. Die taalonderwyser se rot as fasiliteerder van leer in kommunikatiewe FAfrikaanstaalonderrig in die interaktiewe klaskamer met klem op leerdergesentreerde onderrig is uiteengesit. Daar is verder aangetoon dat daar ten opsigte van die rot van die onderwyser 'n paradigmatiese verskuiwing moet plaasvind, veral noudat beginsels van uitkomsgebaseerde onderrig wat deel van kurrikulum 2005 vorm, in 1998/1999 in aile Suid-Afrikaanse skole ingestel is. Die onderwyser is nou 'n fasiliteerder van kennis, nie 'n oordraer daarvan nie. Belangrike aspekte van leer wat leerders se tweedetaalleer be'invloed, is bespreek, byvoorbeeld klaskamerkommunikasie, fasilitering, suggestopedia, faktore wat begrip van leerstof be'invloed, onderwyser - en leerdergedragswyses, positiewe /eeratmosfeer, behandeling van leerderfoute, Jeerderpersepsies, kommunikatiewe strategiee en evalueringsmetodes. 'n Verskeidenheid taallesse wat op T2-Afrikaans en die T2-taalklaskamer betrekking het, en wat verskillende onderrigteoriee, uitkomsgebaseerde onderrig en die ses taalvaardighede integreer, word in hoofstuk 5 ge'illustreer.
In this study it is shown why the discovery model of language learning is the appropriate model for effective language learning. The communicative teaching approach, classroom-negotiation and the importance of the process syllabus in second language acquisition is discussed. The language teacher's role as facilitator of learning, in communicative L2 - Afrikaans language teaching in the interactive classroom with a learner-centered focus is explained. It is further shown that the role of the teacher must undergo a paradigm shift especially now that principles of outcomes based education which forms part of curriculum 2005 has been introduced into all schools in South Africa in 1998/1999. The teacher is now a facilitator of knowledge and not a transmitter thereof. Important aspects of learning that influence learners' second language learning are discussed, for example classroom communication, facilitation, suggestopedia, factors that influence the understanding of subject matter, teacher and learner behaviours, positive learning atmosphere, treatment of Ieamer errors, learner perceptions, communicative strategies and methods of evaluation. A variety of language lessons which integrate various teaching theories, outcomes based education and the six language learning skills which are related to L 2-Afrikaans and the L 2-classroom are illustrated in Chapter 5.
Afrikaans and Theory of Literature
M.A. (Afrikaans)
VRZALOVÁ, Monika. « Role sestry ve screeningu deprese u seniorů ». Master's thesis, 2016. http://www.nusl.cz/ntk/nusl-260905.
Texte intégral