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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
81

Teaching and learning the elements of argumentation

Untereiner, Brian 18 June 2013 (has links)
In this study I investigated the interactions of 25 Grade 8 science students as they learned how to construct oral arguments using the Toulmin Argumentation Pattern framework. I collected the data during three recorded small group discussion sessions during a five week Earth Science unit between February and March of 2011. The first session recorded the students’ discussions prior to receiving either argumentation instruction or the science concept instruction. The second session recorded their discussions after receiving an introduction to argumentation and a scaffold, but not concept instruction. During the three weeks preceding the third session, the students received additional argumentation instruction and completed one-third of the Earth Science unit. The results showed the students collectively made more arguments during each subsequent session. The students’ individual arguments showed a correspondence between their purportedly most familiar topics and the most discussed topics. I also found that when students made counter arguments and/or invited or challenged group members to participate, their discussions contained comparatively more argument elements (claims, data and warrants) than discussions containing predominantly collaborative assertions. The key outcome of this study for developing students’ use of the elements of argumentation during classroom discussions was to recognize and incorporate opportunities for the students to tap into their prior-knowledge. To engage students in this process, the results indicate the importance of creating time for discussions relevant to the curriculum and to the students. / Graduate / 0727 / 0279 / 0714 / brianu@uvic.ca
82

Synthesis of fluorinated drug scaffolds using SNAr substitution reactions

Li, Yuqi January 2017 (has links)
Fluorinated arenes are considered valuable in organic chemistry. They display different types of reactivity and physicochemical properties compared to their hydrogen analogues. In this project, our medicinal chemistry programme focused on developing rapidly accessible and modifiable heterocyclic scaffolds. Different classes of fluorinated heteroatom-containing organic compounds including benzothiophenes, (aza)phenoxazines and benzaldehyde phenylhydrazones were synthesised from highly fluorinated aromatic compounds with a diverse range of functional groups appropriate for medicinal chemistry development. Mechanistic studies for heterocyclic scaffold synthesis were discussed in the project. The mechanisms of the ring-forming reactions were elaborated in detail in each chapter. A range of substituents were introduced flexibly into the aromatic heterocycles, which were designed to meet the requirements for biological screening programmes. New compounds were characterized by 1H, 19F and 13C NMR spectroscopy, mass spectrometry and elemental analysis. The X-ray crystal structures of a fluorinated benzothiophene and two benzopyridooxazine derivatives were obtained confirming the structure and substitution pattern. From the heterocyclic scaffolds prepared, 6-benzimidazol-1-yl-benzothiophene derivatives (91), 3-imidazol-1-yl-pyridobenzoxazine derivatives (130) and 4-1-methylpiperazinyl-benzaldehyde phenylhydrazone derivatives (195) acted as hit compounds and demonstrated significant trypanocidal activities. SAR studies were employed in structural modifications on these samples to search for the best activities with highest selectivity.
83

Arcabouços de quitosana/agente antineoplásico: síntese, caracterização e aplicação.

CRUZ, Jackson Borba da. 25 June 2018 (has links)
Submitted by Maria Medeiros (maria.dilva1@ufcg.edu.br) on 2018-06-25T14:25:31Z No. of bitstreams: 1 JACKSON BORBA DA CRUZ - TESE (PPGCEMat) 2015.pdf: 4572910 bytes, checksum: 529c14d2c73d94769063607a9a287e65 (MD5) / Made available in DSpace on 2018-06-25T14:25:31Z (GMT). No. of bitstreams: 1 JACKSON BORBA DA CRUZ - TESE (PPGCEMat) 2015.pdf: 4572910 bytes, checksum: 529c14d2c73d94769063607a9a287e65 (MD5) Previous issue date: 2015-05-22 / As neoplasias constituem um conjunto de doenças que se caracterizam por uma massa anormal de tecido com crescimento descontrolado e excessivo em relação aos demais tecidos normais. De acordo com o comportamento biológico, elas podem ser classificadas em benignas ou malignas (câncer). Segundo o Instituto Nacional de Câncer (INCA), são esperados 576 mil casos novos de câncer para 2014 e 2015 no Brasil. O combate ao câncer é feito com medidas preventivas, diagnóstico precoce e tratamento. O sistema de liberação controlada de fármacos através da utilização de biomateriais poliméricos associados a compostos com ação antineoplásica pode ser empregado como alternativa de tratamento para esta patologia. Desta forma, este trabalho tem como objetivo a síntese e caracterização de arcabouços de quitosana utilizados como carreadores da droga antitumoral (1,4- Naftoquinona), cuja taxa de liberação poderá ser controlada pela utilização de um agente reticulante como o tripolifosfato de sódio (TPP), com a perspectiva da confecção de um sistema de liberação controlada de fármacos antitumorais. O método consiste na solubilização da quitosana em ácido acético, adição do fármaco, congelamento, liofilização e reticulação com TPP. Todas as amostras foram caracterizadas por Difração de Raios X (DRX), Microscopia Eletrônica de Varredura (MEV), Espectroscopia de Energia Dispersiva de Raios X (EDS), Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR) e Biodegradação Enzimática, A microscopia (MEV) evidenciou a formação de arcabouços porosos de quitosana (Q), quitosana com TPP (QT), quitosana com 1,4 – Naftoquinona (QN) e quitosana com TPP e 1,4 – Naftoquinona (QNT). Já no EDS foi observada a presença de elementos químicos como sódio, fósforo, nitrogênio, carbono e oxigênio. A reticulação dos arcabouços, comprovada pelo FTIR, DRX, Termogravimetria, Grau de Intumescimento e EDS, aumentou a taxa de degradação dos mesmos demonstrada pelo ensaio de Biodegradação Enzimática. A incorporação do fármaco foi confirmada por DRX, FTIR, Grau de Intumescimento e Termogravimetria. Desta forma, pode-se concluir que houve à formação de arcabouços reticulados e não reticulados porosos, com propriedades morfológicas e físico-químicas que podem contribuir para carrear fármacos antineoplásicos, sendo possível controlar a taxa de degradação dos mesmos e consequentemente a liberação do fármaco. / The neoplasias are a group of disorders characterized by an abnormal mass of tissue which has uncontrolled and excessive growth when compared to normal tissue. According to their biological behavior, they can be classified as benign or malignant (cancer). According to the National Cancer Institute (NCI), it is expected that there will be 576,000 new cancer cases in Brazil during 2014 and 2015. The fight against cancer is done with preventive measures, early diagnosis and treatment. The controlled release system of drugs through the use of polymeric biomaterials associated with the compounds that have an antineoplastic action can be used as an alternative treatment for this disease. Thus, this work has as the objective, the synthesis and characterization of chitosan scaffolds used as carriers for antitumor drugs (1,4 Naftoquinona), whose release rate can be controlled by using a crosslinking agent such as sodium tripolyphosphate (TPP), with the prospect of making a controlled release system for antitumor drugs. The method comprises in the solubility of chitosan in acetic acid, drug addition, freezing the material, lyophilization and crosslinking with TPP. All samples were characterized by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Enzymatic Biodegradation. The Microscopy (SEM) showed the formation of porous scaffolds of chitosan (Q), chitosan with TPP (CT), chitosan with 1.4 - Naftoquinona (QN) and chitosan with TPP and 1.4 - Naftoquinona (QNT). EDS showed the presence of chemical elements such as sodium, phosphorus, nitrogen, carbon and oxygen. The crosslinking of the scaffolds, proven by FTIR, XRD, Thermogravimetry, Degree of Swelling and EDS, increased its rate of degradation thereof, as demonstrated by the Enzymatic Biodegradation test. The incorporation of the drug was confirmed by XRD, FTIR, Degree of Swelling and Thermogravimetry. Thus, it can be concluded that there was the formation of crosslinked and non-crosslinked porous scaffolds, with morphological and physicochemical properties that can contribute to the carrying of antineoplastic drugs, being possible to control their degradation rate and consequently drug release.
84

A desmineralização/ descelularização dentária na confecção de scaffold natural / Demineralization/ decellularization for natural teeth scaffold

Iwamoto, Luciana Aparecida de Sousa [UNIFESP] January 2015 (has links) (PDF)
Submitted by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-27T19:41:41Z No. of bitstreams: 1 Publico-NOVO-21.pdf: 2987989 bytes, checksum: fedc0b7588511ac9f1b74f18e86aed33 (MD5) / Approved for entry into archive by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-27T19:42:44Z (GMT) No. of bitstreams: 1 Publico-NOVO-21.pdf: 2987989 bytes, checksum: fedc0b7588511ac9f1b74f18e86aed33 (MD5) / Made available in DSpace on 2016-06-27T19:42:44Z (GMT). No. of bitstreams: 1 Publico-NOVO-21.pdf: 2987989 bytes, checksum: fedc0b7588511ac9f1b74f18e86aed33 (MD5) Previous issue date: 2015 / Agência Brasileira de Cooperação (ABC) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Rede Ibero-Americana de Biofabricação / Introdução: A Engenharia Tecidual (ET) é uma ciência multidisciplinar que visa produzir órgãos e partes humanas substitutas acometidas por lesões traumáticas, doenças degenerativas ou agenesias. Uma das suas etapas é a produção de arcabouços biocompatíveis para aplicação na Medicina Regenerativa. Estas estruturas são conhecidas como scaffolds, que apresentam macrogeometria semelhante ao tecido original, em textura e porosidade e direcionam o comportamento das células que serão semeadas. A recuperação da integridade anatômica e funcional de tecidos lesados garante a sobrevivência dos seres vivos e o tratamento de perdas extensas é desafiador. Objetivo: Avaliar a eficiência para desmineralizar e descelularizar dentes viabilizando-os como scaffolds naturais. Métodos: As amostras foram submetidas a um tratamento com soluções desmineralizadoras/descelularizadoras. Foram usadas 5 soluções: G1-Formol 10% controle, EDTA 28% para desmineralização nos quatro grupos; G2- hipoclorito de sódio 2,5%; e G3-peróxido de hidrogênio 9%; G4- hipoclorito de sódio 2,5% associado com detergente enzimático; G5- detergente enzimático associado a peróxido de hidrogênio 9%. A evolução da desmineralização e descelularização foi acompanhada durante 12 semanas, por meio de pesagem, técnicas analíticas MEV (Microscopia eletrônica de Varredura), fotografia e radiografia. As amostras foram pesadas a cada sete dias para controle da perda de mineral. Os resultados receberam análise estatística de variância de Friedman, Kruskal-Wallis, Resumo xix Teste do Quiquadrado e Teste exato de Fisher. Foi fixado em 0,05 ou 5% o nível de rejeição da hipótese de nulidade. Conclusão: O grupo 5 mostrouse microscopicamente a melhor solução, mesmo mantendo em 30% das amostras resíduos biológicos. / Tissue Engineering (TE) is a multidisciplinary science that aims to produce replacement organs and parts affected by trauma, degenerative diseases or agenesis. One of its goals is to produce biocompatible scaffolds for application in regenerative medicine. These structures are known as scaffolds, presenting three-dimensional shape similar to the original tissue in texture and porosity and directing the behavior of cells to be seeded. The recovery of anatomical and functional integrity of damaged tissues ensures the survival of living beings and the treatment of extensive losses is challenging. Objective: Get decelullarized and demineralized teeth to make them feasible as natural scaffolds. Methods: The samples will be subjected to a treatment with demineralizing/decelularizing solutions. 4 different solutions were used (14% EDTA, 2.5% sodium hypochlorite, hydrogen peroxide and 9% and one group of control (10% formaldehyde). The evolution of demineralization/decellularization was monitored for 90 days through the use of electron scanning microscopy, X-ray and photography. Samples’ weights were measured each seven days to control the mineral loss. Results were subjected to statistical analysis of variance, KruskalWallis test Wilcoxan and Chi-square Test. Was fixed at 0,05 or 5% rejection level of the null hypothesis. / FAPESP: 07/58856-7 / FAPESP: 07/59488-1 / FAPESP: 07/51227-4 / CNPq: 573661/2008-1 / FAPESP: 08/57860-3
85

Musiken i förskolan : Hur pedagoger beskriver musikens betydelse i förskolan och musik som ett pedagogiskt redskap och stöd för att stimulera prosocialt beteende / The role of music in preeschool : How educators describe the importance of music in preschool and the role of music as an educational tool in stimulating the prosocial behavior in children.

Roselius, Ellinore, Nyman, Elisabeth January 2018 (has links)
Abstrakt Pedagogernas roll i förskolan är att använda sig av så många olika redskap och stöd som möjligt för att alla barn ska utvecklas på bästa sätt och efter sina förutsättningar. Musiken kan ses som ett sådant redskap och stöd. Kunskaper hos pedagoger om att utveckling inom ett område kan innebära utveckling inom ett annat område är betydelsefullt. Genom en ökad musikkompetens hos pedagoger så ges barnen fler redskap att exempelvis uttrycka sig, inhämta kunskap och utvecklas socialt.   Syftet med studien har varit att undersöka hur pedagoger beskriver musikens betydelse i förskolan och som ett pedagogiskt redskap och stöd för att utveckla prosocialt beteende. Prosociala handlingar definieras enligt Persson (2004) som handlingar som gynnar en annan person exempelvis hjälpa, trösta och dela med sig. Studien har både en kvantitativ och en kvalitativ forskningsansats. En jämförelse har gjorts mellan traditionella förskolor och musikförskolor för att se om det finns likheter och skillnader i hur pedagogerna använder musik i förskolan. Det teoretiska ramverk som använts vid analys av resultatet är det sociokulturella perspektivet.   Resultatet visar att majoriteten av pedagogerna anser att musik främst har betydelse för barns språkutveckling, glädje och gemenskap. I resultatet framkommer att på musikförskolorna ses musik i ett något vidare perspektiv genom att pedagogerna beskriver att musik genomsyrar verksamheten på ett annat sätt än vad pedagogerna på de traditionella förskolorna uttrycker. Majoriteten av pedagogerna beskriver musiken som ett pedagogiskt redskap och stöd i flera olika sammanhang. Det som dock inte framkom i studien var tydliga resultat gällande musik kopplat till prosocialt beteende.
86

Desenvolvimento de nanobiocompÃsitos para aplicaÃÃo em sistemas de liberaÃÃo controlada de fÃrmacos / Development of biocomposites for application in controlled release drug delivery systems

Elayne ValÃrio Carvalho 29 July 2013 (has links)
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Nos Ãltimos vinte anos, o campo de biomateriais à base de fosfato de cÃlcio tem crescido rapidamente, desempenhando um papel-chave como substituinte Ãsseo. A hidroxiapatita (HA) apresenta semelhanÃa quÃmica e estrutural com a fase mineral dos ossos e dos dentes, à biocompatÃvel e osteocondutiva, tem excelente afinidade quÃmica e biolÃgica com os tecidos Ãsseos e tem aplicaÃÃes biomÃdicas importantes como preenchimento de defeitos Ãsseos e em âscaffoldsâ na engenharia de tecidos. Nanocristais de HA foram sintetizados com sucesso por co-precipitaÃÃo e via hidrotÃrmica. Para a caracterizaÃÃo estrutural, tamanho e morfologia das fases obtidas foram utilizadas tÃcnicas de DifraÃÃo de Raios-x (DRX), Espectroscopia na RegiÃo do Infravermelho com Transformada de Fourier (FTIR), AdsorÃÃo/dessorÃÃo de N2, Potencial Zeta (PZ) e Microscopia EletrÃnica de TransmissÃo (TEM). Estruturas mesoporosas foram obtidas com diÃmetros de poros variando entre 12 e 31 nm. Os nanocristais de HA apresentaram uma morfologia definida, em forma de bastÃo, e foram incorporadas a um polÃmero para formaÃÃo de um âscaffoldâ. A droga sinvastatina (SINV), que influencia a regeneraÃÃo Ãssea quando aplicada localmente, foi associada aos biocompÃsitos obtidos. A caracterizaÃÃo dos âscaffoldsâ foi realizada por Microscopia EletrÃnica de Varredura (MEV). / In the last twenty years, the field of biomaterials based on calcium phosphates has grown rapidly, playing a key role as a bone substituent. Hydroxyapatite has chemical and structural similarity to the mineral phase of bone and teeth, is biocompatible and osteoconductive. It has excellent chemical and biological affinity with the bone tissue and important biomedical applications such as filling bone defects and scaffolds in tissues engineering. Hydroxyapatite nanocrystals were successfully synthesized by co-precipitation and hydrothermal route. X-ray diffraction, Fourier-transform infrared spectroscopy, N2 adsorption/desorption, Zeta Potential and Transmission Electron Microscopy were used to structural characterization, size and morphology of the nanoparticles. Mesoporous structures were obtained with pore diameters ranging from 12 to 31 nm. The nanoparticles showed a rod-shaped mophorlogy and were incorporated into a polymer to form a scaffold. The drug simvastatin, which influences bone regeneration when locally applied, was associated with the biocomposite. The characterization of the scaffolds was performed by Scanning Electron Microscopy.
87

Produção e caracterização de scaffolds de diferentes espessuras obtidos por eletrofiação de nanofibra polimérica e proteína. / Production and characterization of electrospun polymeric-protein nanofiber scaffolds with different thicknesses.

Vanessa Tiemi Kimura 26 September 2017 (has links)
A engenharia tecidual visa repor, reparar ou ajudar a regenerar tecidos e órgãos danificados por meio da combinação de biomateriais, biomoléculas e células. Scaffolds de nanofibras biodegradáveis mimetizam a matriz extracelular natural fornecendo uma estrutura ideal para o crescimento celular. Blendas de policaprolactona (PCL) e gelatina são biodegradáveis e proporcionam uma combinação de boas propriedades mecânicas, do PCL, com a hidrofilicidade e caráter que promove a adesão celular, da gelatina. Neste contexto, o objetivo deste trabalho é avaliar a importância das diferentes espessuras de scaffolds eletrofiados em relação às suas propriedades principais. Quatro conjuntos de scaffolds de PCL/gelatina com diferentes espessuras foram produzidos sob as mesmas condições apenas aumentando o tempo de duração do processo de eletrofiação. Os resultados indicam que as espessuras aumentaram proporcionalmente ao tempo de eletrofiação, variando de 100 nm a 300 nm nos períodos de 1 a 3 horas, enquanto a densidade aparente e a porosidade mantiveram-se constantes. As micrografias das membranas revelaram fibras lisas com diâmetros maiores para os scaffolds de menor espessura, e fibras irregulares com diâmetros menores e regiões fundidas ou ligadas para os scaffolds de maior espessura. Além disso, o aumento da espessura melhorou a resistência mecânica e a molhabilidade dos scaffolds. A esterilização por peróxido de hidrogênio não modificou quimicamente a composição das membranas de PCL/gelatina, embora algumas amostras tenham se deformado. As membranas também apresentaram bons resultados de citotoxicidade, melhorando a viabilidade celular, apesar desses valores diminuírem minimamente para os scaffolds de maior espessura, provavelmente devido à maior quantidade de PCL. O teste de adesão não foi conclusivo e deverá ser repetido. / Tissue engineering aims to replace, repair, or helping regenerate damaged tissues and organs through the combination of biomaterials, biomolecules and cells. Biodegradable nanofibrous scaffolds mimic the natural extracellular matrix providing an ideal structure to cellular growth. Blends of polycaprolactone (PCL) and gelatin are biodegradable and provide a combination of good mechanical properties, from PCL, with the hydrophilicity and cell adhesion promoter character, from gelatin. The aim of this work was to evaluate the importance of the thickness of electrospun scaffolds on their key properties. Four sets of PCL/gelatin scaffolds with different thicknesses were produced under the same conditions by simply increasing the time length of electrospinning process. Results indicate that the thickness increases proportionally to the electrospinning time, varying from 100 nm to 300 nm in periods of 1 to 3 hours, while the apparent density and porosity remained constant. Micrographs from the nonwoven mats revealed smooth fibers with larger diameters in the thinner scaffold, and irregular fibers with smaller diameters and molten or bonded regions as the thickness increased. Furthermore, the increase of thickness improved mechanical resistance and wettability of the scaffolds. Plasma sterilization did not modify chemical composition of PCL/gelatin membranes, although some samples have been deformed. Membranes also presented good results for cytotoxicity, improving cell viability, despite these values decreased minimally to the thicker scaffolds, probably due to the higher amount of PCL. Adhesion test was not conclusive and might be repeat.
88

Computational strategies to identify, prioritize and design potential antimalarial agents from natural products

Egieyeh, Samuel Ayodele January 2015 (has links)
Philosophiae Doctor - PhD / Introduction: There is an exigent need to develop novel antimalarial drugs in view of the mounting disease burden and emergent resistance to the presently used drugs against the malarial parasites. A large amount of natural products, especially those used in ethnomedicine for malaria, have shown varying in-vitro antiplasmodial activities. Facilitating antimalarial drug development from this wealth of natural products is an imperative and laudable mission to pursue. However, the limited resources, high cost, low prospect and the high cost of failure during preclinical and clinical studies might militate against pursue of this mission. Chemoinformatics techniques can simulate and predict essential molecular properties required to characterize compounds thus eliminating the cost of equipment and reagents to conduct essential preclinical studies, especially on compounds that may fail during drug development. Therefore, applying chemoinformatics techniques on natural products with in-vitro antiplasmodial activities may facilitate identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and high likelihood for development into antimalarial drugs. In addition, unique structural features mined from these natural products may be templates to design new potential antimalarial compounds. Method: Four chemoinformatics techniques were applied on a collection of selected natural products with in-vitro antiplasmodial activity (NAA) and currently registered antimalarial drugs (CRAD): molecular property profiling, molecular scaffold analysis, machine learning and design of a virtual compound library. Molecular property profiling included computation of key molecular descriptors, physicochemical properties, molecular similarity analysis, estimation of drug-likeness, in-silico pharmacokinetic profiling and exploration of structure-activity landscape. Analysis of variance was used to assess statistical significant differences in these parameters between NAA and CRAD. Next, molecular scaffold exploration and diversity analyses were performed on three datasets (NAA, CRAD and malarial data from Medicines for Malarial Ventures (MMV)) using scaffold counts and cumulative scaffold frequency plots. Scaffolds from the NAA were compared to those from CRAD and MMV. A Scaffold Tree was also generated for all the datasets. Thirdly, machine learning approaches were used to build four regression and four classifier models from bioactivity data of NAA using molecular descriptors and molecular fingerprints. Models were built and refined by leave-one-out cross-validation and evaluated with an independent test dataset. Applicability domain (AD), which defines the limit of reliable predictability by the models, was estimated from the training dataset and validated with the test dataset. Possible chemical features associated with reported antimalarial activities of the compounds were also extracted. Lastly, virtual compound libraries were generated with the unique molecular scaffolds identified from the NAA. The virtual compounds generated were characterized by evaluating selected molecular descriptors, toxicity profile, structural diversity from CRAD and prediction of antiplasmodial activity. Results: From the molecular property profiling, a total of 1040 natural products were selected and a total of 13 molecular descriptors were analyzed. Significant differences were observed between the natural products with in-vitro antiplasmodial activities (NAA) and currently registered antimalarial drugs (CRAD) for at least 11 of the molecular descriptors. Molecular similarity and chemical space analysis identified NAA that were structurally diverse from CRAD. Over 50% of NAA with desirable drug-like properties were identified. However, nearly 70% of NAA were identified as potentially "promiscuous" compounds. Structure-activity landscape analysis highlighted compound pairs that formed "activity cliffs". In all, prioritization strategies for the natural products with in-vitro antiplasmodial activities were proposed. The scaffold exploration and analysis results revealed that CRAD exhibited greater scaffold diversity, followed by NAA and MMV respectively. Unique scaffolds that were not contained in any other compounds in the CRAD datasets were identified in NAA. The Scaffold Tree showed the preponderance of ring systems in NAA and identified virtual scaffolds, which maybe potential bioactive compounds or elucidate the NAA possible synthetic routes. From the machine learning study, the regression and classifier models that were most suitable for NAA were identified as model tree M5P (correlation coefficient = 0.84) and Sequential Minimization Optimization (accuracy = 73.46%) respectively. The test dataset fitted into the applicability domain (AD) defined by the training dataset. The “amine” group was observed to be essential for antimalarial activity in both NAA and MMV dataset but hydroxyl and carbonyl groups may also be relevant in the NAA dataset. The results of the characterization of the virtual compound library showed significant difference (p value < 0.05) between the virtual compound library and currently registered antimalarial drugs in some molecular descriptors (molecular weight, log partition coefficient, hydrogen bond donors and acceptors, polar surface area, shape index, chiral centres, and synthetic feasibility). Tumorigenic and mutagenic substructures were not observed in a large proportion (> 90%) of the virtual compound library. The virtual compound libraries showed sufficient diversity in structures and majority were structurally diverse from currently registered antimalarial drugs. Finally, up to 70% of the virtual compounds were predicted as active antiplasmodial agents. Conclusions:Molecular property profiling of natural products with in-vitro antiplasmodial activities (NAA) and currently registered antimalarial drugs (CRAD) produced a wealth of information that may guide decisions and facilitate antimalarial drug development from natural products and led to a prioritized list of natural products with in-vitro antiplasmodial activities. Molecular scaffold analysis identified unique scaffolds and virtual scaffolds from NAA that possess desirable drug-like properties, which make them ideal starting points for molecular antimalarial drug design. The machine learning study built, evaluated and identified amply accurate regression and classifier accurate models that were used for virtual screening of natural compound libraries to mine possible antimalarial compounds without the expense of bioactivity assays. Finally, a good amount of the virtual compounds generated were structurally diverse from currently registered antimalarial drugs and potentially active antiplasmodial agents. Filtering and optimization may lead to a collection of virtual compounds with unique chemotypes that may be synthesized and added to screening deck against Plasmodium.
89

Co-delivery of Two Growth Factors From Combined PLGA and PLLA/PCL Microsphere Scaffolds for Spinal Cord Injury Repairs

Li, Zhongxuan January 2014 (has links)
The purpose of this study is to demonstrate the effectiveness of spheres-in-tube structured scaffolds to sequentially deliver two biomolecules during two phases of tissue regeneration following spinal cord injury (SCI). Scaffolds were synthesized of a poly (lactic-co-glycolic acid) (PLGA) base combined with Poly (L-lactic acid) / Poly (ε-caprolactone) (PLLA/PCL) microspheres. The scaffolds are constructed by leveraging the different solubilities of PLGA, PLLA and PCL in super critical carbon dioxide and ethyl acetate during fabrication processes. Microspheres can reduce the pore size and porosity of PLGA scaffolds; this enhances their mechanical strength and enables them to provide long-term treatment without collapse. The release of the epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-b) are being used to study the release profiles of the designed scaffolds. The analysis shows that FGF-b is released from high porosity PLGA base as the first delivery vehicle and completes the release in the first week. PLLA or PCL microspheres, having the property of sustainably delivering encapsulated EGF in 36 days, are used as the second drug delivery vehicle. FGF-b released within the first week can mimic biomolecules used to protect the surviving neurons and promote the development of sprout axons. The sustained release of EGF from microspheres is used for long-term therapy to differentiate multipotent cells into determined types at the injury site. The results demonstrate that these enhanced parameters along with the ability of sequential co-delivery of growth factors, make these designed scaffolds a promising candidate in SCI studies.
90

Digitally Curious: A Qualitative Case Study of Students’ Demonstrations of Curiosity in a Technology-Rich Learning Environment

McLeod, Julie Kiser 08 1900 (has links)
Curiosity is an important construct for educators as it is connected with knowledge and higher-order thinking, goal-oriented behavior, motivation, and persistence. It is also negatively correlated with boredom and anxiety. While research documents this strong connection between learning and curiosity, no studies existed exploring curiosity in a technology-rich learning environment. The purpose of this study is to identify and examine whether students demonstrate curiosity in a sixth grade mathematics classroom with technology-integrated learning and if so, how and why. Technology-rich work was designed for students and included in the study to examine students’ demonstrations of curiosity while learning mathematical procedural knowledge, conceptual knowledge and problem solving knowledge. A case study methodology was used with 13 students purposefully selected from a Title I sixth grade class to participate. Data were collected from interviews using a semi-structured interview protocol and triangulated with observations and students’ reflective writings. Interviews were transcribed and coded. A total of 60 codes and four categories were identified. Three themes emerged: 1) digital play; 2) welcome and unwelcome scaffolds; and 3) action is power; power follows ideas. These themes identified ways in which students demonstrated curiosity in the sixth grade mathematics classroom and thus can inform educators.

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