Дисертації з теми "Lead Candidate"
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Wang, Yunzhi (Yunzhi Diana). "Static corrosion of candidate alloys for the lead-bismuth fast reactor." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/45266.
Повний текст джерелаIncludes bibliographical references (leaves 41-42).
This project examined the corrosion rates and mechanisms of two candidate alloys for use in Lead-bismuth Eutectic (LBE) cooled fast nuclear reactors. The two alloys examined were T91 and Fe-12Cr-2Si. An experimental study was performed to analyze the static corrosion on the two alloys. For the experiment, the polished samples of the two alloys were heated in LBE for 166 hours at 700 The heating conditions, such as temperature, oxygen levels, and moisture levels were monitored closely throughout the duration of the experiment. During the heating process, hydrogen gas was bubbled into the LBE, creating a highly reducing environment. Argon was used as a cover gas. Upon removal from the furnace, the alloy samples were examined via optical microscopy, scanning electron microscopy, and X-ray diffraction analysis. Examination of the samples found no observable corrosion effects on the Fe-12Cr-2Si samples and a thin layer of magnetite on the T91 sample.
by Yunzhi (Diana) Wang.
S.B.
Kunkle, Jamie Motta A. T. "Structure of oxide layers formed on candidate steel alloys exposed to flowing lead-bismuth eutectic for Generation IV reactor applications." [University Park, Pa.] : Pennsylvania State University, 2009. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-3462/index.html.
Повний текст джерелаSandhaus, Shayna. "Drug Candidate Discovery: Targeting Bacterial Topoisomerase I Enzymes for Novel Antibiotic Leads." FIU Digital Commons, 2017. https://digitalcommons.fiu.edu/etd/3561.
Повний текст джерелаLizzi, Federica <1981>. "Drug Discovery for Neglected Tropical Diseases: Design and Synthesis of Lead Candidates for the Treatment of Trypanosomatid Diseases." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2010. http://amsdottorato.unibo.it/2942/.
Повний текст джерелаMpamhanga, Chidochangu P. "Development and implementation of a virtual screening strategy for the discovery of CJD lead candidates and their biological evaluation." Thesis, University of Sheffield, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444256.
Повний текст джерелаAlves, Fernanda [UNESP]. "Estudo in vivo dos efeitos da terapia fotodinâmica, mediada pelo Photothazine® e luz led, sobre Cândida Albicans resistente a Fluconazol." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/97271.
Повний текст джерелаEste estudo avaliou os efeitos da Terapia Fotodinâmica (PDT), mediada pelo Photodithazine® (PDZ) e luz LED, sobre Candida albicans resistente a fluconazol em um modelo de candidose oral induzida. Para isso, camundongos fêmeas de 6 semanas foram imunussuprimidos e inoculados com C. albicans (107 células/mL). Em seguida, aplicou-se 100 mg/L de PDZ (diluído em salina ou hidrogel) na cavidade bucal por 20 min e o dorso lingual foi iluminado (37,5 J/cm² dose de luz). Animais adicionais foram tratados somente com LED ou PDZ. O grupo controle positivo não recebeu nenhum tratamento e, adicionalmente, animais saudáveis receberam tratamento com PDT (n=5). Em seguida, foi feita a recuperação do micro-organismo da língua dos animais. O número de colônias viáveis foi quantificado e os valores de UFC/mL foram determinados. Os animais foram sacrificados e as línguas foram removidas cirurgicamente para análise histológica. Duas colônias de cada animal foram isoladas da placa de cultura para avaliação dos fatores de virulência: adesão e formação de biofilme em superfície abiótica, formas filamentares de crescimento e produção de exoenzimas. Os dados foram analizados por ANOVA (P < 0,05). Os resultados demonstraram que a PDT resultou em redução significativa de C. albicans resistente a fluconazol (1,91 e 1,96 log10) em relação ao grupo controle positivo. Somente a aplicação da luz ou PDZ não reduziu a viabilidade celular. A PDT não ocasionou efeitos adversos no tecido lingual dos animais e reduziu apenas a produção de fosfolipase. A PDT foi efetiva na inativação da C. albicans resistente a fluconazol, sem causar efeitos adversos no tecido lingual.
This study evaluated the effects of Photodynamic Therapy (PDT), mediated by Photodithazine® (PDZ) and LED light, on fluconazole-resistant Candida albicans in a murine model of oral candidosis. For this, six-week-old female mice were immunosuppressed and inoculated with C. albicans (107 células/mL). Then, 100 mg/L of PDZ (diluted in saline or hydrogel) was applied on the oral cavity for 20 min and the dorsum of the tongue was illuminated (37.5 J/cm2 of fluence). The use of PDZ or light only was also investigated. Additionally, healthy animals received treatment with PDT. Positive control animals did not receive any treatment and negative control animals were not inoculated (n=5). After treatment the dorsum of the tongue was swabbed to recover C. albicans. The yeast colony counts were quantified and the number of CFU/mL was determined. The animals were killed and the tongues were surgically removed for histological analysis. Two yeast colony of each group were isolated from the culture plate for the evaluation of virulence factors: adhesion and biofilm formation in abiotic surface, filamentous forms of growth and production of exoenzymes. Data were analyzed by ANOVA (P < 0.05). PDT resulted in a significant reduction of fluconazole-resistant C. albicans (1.91 e 1.96 log10). The application of PDZ or LED only did not reduce the cell viability. PDT did not cause adverse effects in the local mucosa and it was able to reduce only phospholipase production. PDT was effective in the inactivation of fluconazole-resistant C. albicans without harming the tongue tissue.
Alves, Fernanda. "Estudo in vivo dos efeitos da terapia fotodinâmica, mediada pelo Photothazine® e luz led, sobre Cândida Albicans resistente a Fluconazol /." Araraquara : [s.n.], 2013. http://hdl.handle.net/11449/97271.
Повний текст джерелаBanca: Gilberto Ubida Leite Braga
Banca: Ewerton Garcia de Oliveira Mima
Resumo: Este estudo avaliou os efeitos da Terapia Fotodinâmica (PDT), mediada pelo Photodithazine® (PDZ) e luz LED, sobre Candida albicans resistente a fluconazol em um modelo de candidose oral induzida. Para isso, camundongos fêmeas de 6 semanas foram imunussuprimidos e inoculados com C. albicans (107 células/mL). Em seguida, aplicou-se 100 mg/L de PDZ (diluído em salina ou hidrogel) na cavidade bucal por 20 min e o dorso lingual foi iluminado (37,5 J/cm² dose de luz). Animais adicionais foram tratados somente com LED ou PDZ. O grupo controle positivo não recebeu nenhum tratamento e, adicionalmente, animais saudáveis receberam tratamento com PDT (n=5). Em seguida, foi feita a recuperação do micro-organismo da língua dos animais. O número de colônias viáveis foi quantificado e os valores de UFC/mL foram determinados. Os animais foram sacrificados e as línguas foram removidas cirurgicamente para análise histológica. Duas colônias de cada animal foram isoladas da placa de cultura para avaliação dos fatores de virulência: adesão e formação de biofilme em superfície abiótica, formas filamentares de crescimento e produção de exoenzimas. Os dados foram analizados por ANOVA (P < 0,05). Os resultados demonstraram que a PDT resultou em redução significativa de C. albicans resistente a fluconazol (1,91 e 1,96 log10) em relação ao grupo controle positivo. Somente a aplicação da luz ou PDZ não reduziu a viabilidade celular. A PDT não ocasionou efeitos adversos no tecido lingual dos animais e reduziu apenas a produção de fosfolipase. A PDT foi efetiva na inativação da C. albicans resistente a fluconazol, sem causar efeitos adversos no tecido lingual.
Abstract: This study evaluated the effects of Photodynamic Therapy (PDT), mediated by Photodithazine® (PDZ) and LED light, on fluconazole-resistant Candida albicans in a murine model of oral candidosis. For this, six-week-old female mice were immunosuppressed and inoculated with C. albicans (107 células/mL). Then, 100 mg/L of PDZ (diluted in saline or hydrogel) was applied on the oral cavity for 20 min and the dorsum of the tongue was illuminated (37.5 J/cm2 of fluence). The use of PDZ or light only was also investigated. Additionally, healthy animals received treatment with PDT. Positive control animals did not receive any treatment and negative control animals were not inoculated (n=5). After treatment the dorsum of the tongue was swabbed to recover C. albicans. The yeast colony counts were quantified and the number of CFU/mL was determined. The animals were killed and the tongues were surgically removed for histological analysis. Two yeast colony of each group were isolated from the culture plate for the evaluation of virulence factors: adhesion and biofilm formation in abiotic surface, filamentous forms of growth and production of exoenzymes. Data were analyzed by ANOVA (P < 0.05). PDT resulted in a significant reduction of fluconazole-resistant C. albicans (1.91 e 1.96 log10). The application of PDZ or LED only did not reduce the cell viability. PDT did not cause adverse effects in the local mucosa and it was able to reduce only phospholipase production. PDT was effective in the inactivation of fluconazole-resistant C. albicans without harming the tongue tissue.
Mestre
Luz, Felipe Brunatto da. "Aplicação de Terapia Fotodinâmica (PDT) usando luz LED azul sobre culturas de Candida albicans - in vitro." Universidade Federal de Pelotas, 2014. http://repositorio.ufpel.edu.br:8080/handle/prefix/3471.
Повний текст джерелаMade available in DSpace on 2017-06-01T15:06:07Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Aplicação de Terapia Fotodinâmica (PDT) usando luz LED azul sobre culturas de candida albicans in vitro.pdf: 903559 bytes, checksum: d57e4b195e3104bd65820ee04210e36d (MD5) Previous issue date: 2014-08-29
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
O fungo Candida albicans é frequentemente encontrado como componente da microbiota da cavidade oral, sendo agente etiológico da candidíase eritematosa crônica (estomatite por dentadura). Condição esta, uma infecção oportunista, de caráter crônico que acomete grande parte dos usuários de próteses. O tratamento tradicional com antifúngicos, muitas vezes é duradouro, colaborando para o surgimento de cepas resistentes desse fungo. Assim sendo, torna-se necessária uma alternativa de tratamento efetiva contra a candidíase oral e que não apresente efeitos colaterais. O objetivo desse estudo foi desenvolver um novo dispositivo a partir de um fotopolimerizador odontológico, baseado na tecnologia LED com emissão de luz azul. Além disso, verificar a ação da PDT com azul de metileno associada ao uso dessa fonte sobre culturas de Candida albicans. Após o crescimento e identificação das colônias foram selecionadas 04 cepas de Candida albicans e 01 cepa ATCC (62342) e realizadas diluições obedecendo-se a escala 0,5 de Macfarland (1x108 UFC). Desse inóculo, foram colocados 100 µl em cada poço de uma placa de microtitulação de 96 poços. As amostras das colônias de Candida albicans foram distribuídas em triplicata nas placas de cultura. No grupo testado foram colocados 90 µl de PBS, adicionado a 10 µl de azul de metileno. As placas foram incubadas durante 30 minutos e, após esse período, foi realizada a irradiação com LED azul. Para realizar a PDT a placa foi dividida em 6 setores de dimensões iguais. Cada setor foi irradiado durante 6 minutos na dosimetria de 122 J/cm2, potência de 260 mW e comprimento de onda de 455 nm em aplicação única, totalizando 36 minutos de aplicação em cada placa. Após esse desafio, foram realizadas diluições seriadas 1:10 em 4 alíquotas sucessivas. Dessa diluição foram semeados 25 µl em placas de Petri e incubadas a 37ºC por 48 horas. Após esse período foram feitas as contagens das colônias por dois examinadores previamente treinados e calibrados. Os resultados foram analisados estatisticamente usando ANOVA seguido por teste de Tukey com 5% de nível de significância e não mostraram diferença estatisticamente significante (p>0,05) entre os diferentes grupos e o grupo controle. Constatando-se que a PDT usando fonte de luz LED é uma alternativa viável, no entanto no presente estudo não foi possível constatar a ação dessa terapia.
The fungus Candida albicans is often found as the microflora of the oral cavity component, as the etiological agent of erythematous candidiasis (denture stomatitis), this condition is an opportunistic infection, a chronic condition that affects most users of prostheses. Traditional treatment with antifungals, often lasting, contributing to the manifestation of resistant strains of this fungus. Therefore, it is necessary effective alternative treatment for oral candidiasis and who does not produce side effects. The aim of this study was to develop a new device from a dental curing light, based on the LED technology with blue light emission. As well, check the action of PDT with methylene blue associated with the use of this source on cultures of Candida albicans. After the growth and identification of colonies were selected 04 strains of Candida albicans and 01strain ATCC (62342) and made dilutions obeying the scale of 0.5 Macfarland (1x108 CFU). In this inoculum, 100 mL were placed in each well of a 96-well microtiter plate wells. Samples of colonies of Candida albicans were triplicate distributed in culture plates. On the test group 90 µl of PBS, added to 10 µl of methylene blue were placed. The plates were incubated for 30 minutes and, thereafter, irradiation was performed with blue LED. To perform PDT the plate was divided into 6 sectors of equal dimensions. Each sector was irradiated for 6 minutes dosimetry of 122 J/cm² power of 260 mW and wavelength of 455 nm in a single application, totaling 36 minutes of application on each plate. After this challenge, serial dilutions 1:10 in 4 successive aliquots were performed. This dilution were seeded 25 µl in Petri dishes and incubated at 37 ° C for 48 hours. After this period the numbers of colonies were made by two previously trained and calibrated examiners. The results were statistically analyzed using ANOVA followed by Tukey test at 5% significance level and showed no statistically significant difference (p> 0.05) between the different groups and the control group. The authors verified that PDT using LED light source is a viable alternative, however in this study it was not possible to observe the action of this therapy.
Oliveira, Lucas Portela. "Síntese, caracterização de fosfato de prata (Ag3PO4) e sua ação contra Candida albicans associado com luz LED /." Araraquara, 2018. http://hdl.handle.net/11449/157070.
Повний текст джерелаResumo: Há diversas possibilidades para o controle microbiano, dentre elas, o uso de microcristais associados à prata (Ag), e a inativação fotodinâmica antimicrobiana (do inglês, aPDI). Devido à capacidade de fotoexcitação no comprimento de onda de luz azul, fosfato de prata (Ag3PO4) foi submetido à exposição a luz em 455nm. Este trabalho teve como objetivo sintetizar, caracterizar e verificar a capacidade fotocatalítica e antimicrobiana dos microcristais de Ag3PO4, utilizando culturas de C. albicans em suspensão e biofilme, na presença e ausência de luz. Os microcristais foram sintetizados pelo método da co-precipitação, e foram determinados o "gap" de energia e o espectro de absorção do material através de análise de espectro de UVVIS. Para caracterizar Ag3PO4, realizou-se a difração de raios-X (DRX), microscopia eletrônica de varredura por emissão de campo (MEV-EC) e atividade fotocatalítica (degradação de rodamina) após 4 exposições à luz. Para os ensaios microbiológicos (UFC/mL), determinou-se a concentração fungicida mínima (CFM) em suspensão e biofilme, na ausência e presença de luz (55,8 J/cm²). Para análise dos resultados, aplicou-se o teste de análise de variância de dois fatores, com teste posterior de Tukey. Os resultados demonstraram que o espectro de absorção abrange a faixa azul do comprimento de onda, apesar do maior sinal estar localizado na região de luz UV. Nos espectros de DRX observou-se a produção de prata cúbica e hexagonal no decorrer das exposições, juntament... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: There are several possibilities for microbial control, among them the use of microcrystals associated with silver (Ag), and antimicrobial photodynamic inactivation (aPDI). Due to the ability of photoexcitation in the blue light wavelength, silver phosphate (Ag3PO4) was subjected to light exposure at 455nm. Thus, the aim was to synthesize, characterize and verify the photocatalytic and antimicrobial capacity of Ag3PO4 microcrystals using cultures of C. albicans in planktonic and biofilm form, in the presence and absence of light. Microcrystals were synthesized by the coprecipitation method, the energy band gap and the absorption spectrum of the material were determined by UV-VIS spectrum analysis. To characterize Ag3PO4, Xray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and photocatalytic activity (rhodamine degradation) were performed after 4 exposures to light. For the microbiological tests (CFU/mL), the minimum fungicidal concentration (MFC) in planktonic and biofilm was determined, in the absence and presence of light (55.8 J/cm²). To analyze the results, a two-way analysis of variance (ANOVA) was applied, followed by Tukey post-test. The results showed the absorption spectrum covers the blue wavelength range, although the largest peak is located in the UV light region. The XRD spectra produced cubic and hexagonal silver during the exposures, with an increase of amorphous material. The microcrystal size was observed (0.12 μm) by FE-SEM images, wi... (Complete abstract click electronic access below)
Mestre
Geurtz, Lea [Verfasser]. "Speziesverteilung und Resistenzepidemiologie von Candida Spezies aus einer multizentrischen Blutkulturstudie - Evaluierung eines semiautomatisierten Verfahrens (VITEK 2) zur Resistenztestung / Lea Geurtz." Köln : Deutsche Zentralbibliothek für Medizin, 2010. http://d-nb.info/1009194879/34.
Повний текст джерелаLima, Gustavo Machado Alvares de. "Estudos estruturais de enzimas da via de biossíntese de folatos de Xanthomonas albilineans para o desenvolvimento de novos candidatos a agroquímicos para a cultura de cana-de-açúcar." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-31012018-164124/.
Повний текст джерелаThe importance of sugarcane as a source of renewable energy has pushed researchers to search for improvements in the process of cultivation and processing of the plant, looking after increase the productivity of sugarcane crops. Among known facts that limits sugarcane production, we highlight the occurrence of plant diseases, such as leaf scald, a bacterial disease caused by Xanthomonas albilineans. This disease decreases the energetic value of the broth extracted from the cane, and the absence of chemical or biological treatment entails the need for early refresh sugarcane plantations, causing significant losses for Brazilian agribusiness. Therefore, the economic interest in the development of new molecules capable of acting as agricultural defenses with efficiency and specificity is motivating. Acting on the essential biochemical pathways of the pathogen is a recurring strategy in the development of bioactive molecules. Thus, several inhibitor identification strategies were used. Firstly, the inhibitory potential of molecules from natural or synthetic origins were evaluated in phenotypic assays against the culture of X. albilineans, identifying two nitrothiophene and nitrofuran derivatives capable of inhibiting bacterial growth at 2 mM. In another strategy, the essential pathway of X. albilineans for folate biosynthesis was selected and two proteins of this pathway investigated: 2-amino-4-hydroxy-6-hydroxymethyl dihydropteridine pyrophosphokinase (XaHPPK) and 7,8-dihydroneopterin aldolase (XaDHNA). Both molecular biology and structural biology methods were used to obtain pure and soluble proteins, aiming the obtaining of three-dimensional structures and biochemical characterization of targets. Studies with the XaHPPK protein for kinetic characterization made possible to calculate the Kd apparent (Kd = 97 ± 3 μM) for the substrate 7,8-dihydropterin. Structural biology experiments resulted in a 2.3 Å resolution structure in the space group P212121, available in the PDB under the 5VSP identifier. Structure based drug design for XaHPPK structure, SBDD, were performed using ZINC15 database with hierarchical filters and the Glide docking software. The XaDHNA studies enabled the collection of a set of data at 3.5 Å resolution in the space group I422. The experiments and results obtained in this doctorate increase the knowledge about the folate biosynthesis pathway in X. albilineans and open the way for the discovery of new antibacterial inhibitors using structure based drug design.
Bueno, Renata Vieira. "Estudos estruturais e funcionais da enzima N5, N10 - metilenotetrahidrofolato-desidrogenase-ciclohidrolase de Xanthomonas albilineans aplicados à descoberta de candidatos a inibidores para o tratamento da escaldadura das folhas." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-06062018-092525/.
Повний текст джерелаThe leaf scald disease is a severe condition which affects sugarcane crops. Leaf scald is caused by the Gram-negative bacteria Xanthomonas albilineans and it has a dramatic impact on crop productivity, including the yield reduction and dropping the quality of the juice. The impact of this disease besides the absence of chemical or biological agents to treat it stimulates the research towards the discovery and development of bioactive molecules as lead candidates to new agrochemicals. In this context, the enzyme N5, N10-methylenetetrahydrofolate dehydrogenase-cyclohydrolase (XaFolD) stands out as a potential molecular target. Facing this scenario, the PhD project comprised the structural and functional characterization of X. albilineans FolD (XaFolD) and the screening of molecules to identify inhibitors. For this purpose, integrated studies in structural molecular biology and biological chemistry have been carried out. Suitable protein for crystallization and kinetic assays was produced by heterologous expression. The XaFolD dehydrogenase and cyclohydrolase activities were characterized, revealing KM values of 50 ± 10 µM for N5, N10- methylenetetrahydrofolate, 32 ± 3 µM for N5, N10-methenyltetrahydrofolate, and 688 ± 81 µM for NADP+. The structure of XaFolD in the apo form was elucidated at 2.1 Å resolution and it revealed a protein consisting of 11 alpha helices and 9 beta sheets distributed in the catalytic N-terminal domain and the C-terminal dinucleotide binding domain. Screening of 1,124 fragments by biolayer interferometry (BLI) revealed three ligands, DDD00808259, DDD01305586 and DDD00100784, with determined KD values of 260 µM, 3 mM and 210 M, respectively. Furthermore, a virtual screening was performed to identify XaFolD ligands. As a result, 31 chemically diverse compounds were selected to be evaluated by potency assays. Additionally, phenotypical assays against X. albilineans have been performed and inhibitors were identified. Among them, the compound THP2 presented the highest potency, with a determined value of EC50 equal to 23 ± 2 µM. The structural, kinetic, and biophysical data obtained in this PhD thesis provide the molecular basis for discovering and planning bioactive molecules as agrochemicals to control leaf scald disease.
Alves, Orley Araújo. "Avaliação da eficiência do diodo emissor de luz (LED) emitindo em 460 nm associado à curcumina na fotossensibilização letal de Candida albicans e de Aggregatibacter actinomycetemcomitans: Estudo in vitro." Universidade Federal de Minas Gerais, 2011. http://hdl.handle.net/1843/BUOS-8NWGAV.
Повний текст джерелаCavallin, Mara. "Physiopathologie moléculaire et cellulaire des anomalies du développement du cortex cérébral : le syndrome d'Aicardi WDR81 mutations cause extreme microcephaly and impair mitotic progression in human fibroblasts and Drosophila neural stem cells TLE1, a key player in neurogenesis, a new candidate gene for autosomal recessive postnatal microcephaly Mutations in TBR1 gene leads to cortical malformations and intellectual disability Aicardi syndrome: Exome, genome and RNA-sequencing of a large cohort of 19 patients failed to detect the genetic cause Recurrent RTTN mutation leading to severe microcephaly, polymicrogyria and growth restriction Recurrent KIF2A mutations are responsible for classic lissencephaly Recurrent KIF5C mutation leading to frontal pachygyria without microcephaly Rare ACTG1 variants in fetal microlissencephaly De novo TUBB2B mutation causes fetal akinesia deformation sequence with microlissencephaly: An unusual presentation of tubulinopathy A novel recurrent LIS1 splice site mutation in classic lissencephaly Further refinement of COL4A1 and COL4A2 related cortical malformations Prenatal and postnatal presentations of corpus callosum agenesis with polymicrogyria caused By EGP5 mutation Delineating FOXG1 syndrome from congenital microcephaly to hyperkinetic encephalopathy Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy." Thesis, Sorbonne Paris Cité, 2019. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=2213&f=18201.
Повний текст джерелаMalformations of cortical development (MCD) are a major cause of intellectual disability and drug-resistant epilepsy. Next Generation Sequencing (NGS) has considerably improved the identification of the molecular basis of non-syndromic MCD. However, certain forms, including complex MCD, remain unexplained. My PhD project aimed to improve the understanding of complex MCD using two disorders: Microlissencephaly (MLIS) and Aicardi Syndrome (AIC), the latter associating brain and eye malformations and only reported in girls. Trio Whole Exome Sequencing (WES) performed in 16 MLIS families allowed me to identify and functionally characterize a new MLIS gene, WDR81, in which mutations lead to cell cycle alteration. Moreover, using the same strategy, I was able to identify a pathogenic homozygous variant in TLE1 in a patient from consanguineous family with a postnatal microcephaly, suggestive of a FOXG1-like presentation. Interestingly, TLE1 is a major partner of FOXG1, a gene involved in maintaining the balance between progenitor proliferation and differentiation. In parallel, my work allowed me to redefine the phenotypic spectrum associated with RTTN, EPG5, COL4A1 and COL4A2, TBR1, KIF5C, KIF2A and FOXG1. The second part of my PhD program was aimed at identifying the genetic basis of AIC in an international cohort of 19 patients. After excluding a skewed X chromosome inactivation and the presence of chromosomal rearrangements, I performed WES in trios. The analysis of the data from WES did not allow me to identify any recurrent variants. I therefore tested a new approach combining Whole Genome Sequencing (WGS) and RNA-Sequencing (RNA-Seq) on fibroblast cells. I identified a number of deregulated transcripts implicated in brain and eye development. I compared the results of this analysis with the WGS analysis in order to find variants in these candidate genes. In conclusion, these studies have improved the knowledge of the molecular basis of complex MCD, such as TLE1 in postnatal microcephaly, and revealed the pathogenic mechanisms such as WDR81 in cell cycle progression and EPG5 in endosomes and autophagy. My work has also generated a collection of NGS data (WES, WGS and RNA-Seq) that will be shared in an international consortium to develop new analytical strategies, in particular for the non-coding DNA regions. This novel strategy provides opportunities to improve understanding of the cellular mechanisms involved in brain and eye development
Hähnke, Volker Dirk [Verfasser]. "Text-based similarity searching for hit- and lead-candidate identification / von Volker Dirk Hähnke." 2010. http://d-nb.info/1011435446/34.
Повний текст джерелаShaheen, Tanzia. "Screening lead small molecules for cytokine induction in a human whole blood assay informs candidate adjuvant selection." Thesis, 2018. https://hdl.handle.net/2144/31282.
Повний текст джерелаPo-Chu, Chen, та 陳伯珠. "一.High Throughput Screening of Anti-liver-cancer Drug Candidate from Antrodia Camphorata Mycelia.二.Studies on the Apoptosis Pathway of the Anti-liver-cancer Drug Lead Treated Human Cancer Cell HepG2 at the p53, bax and bcl-2 mRNA Level". Thesis, 2004. http://ndltd.ncl.edu.tw/handle/11880911841117661489.
Повний текст джерела國立中正大學
化學研究所
92
Abstract Antrodia camphorata, “niu-chang-chih”, is a unique species of fungus found in Taiwan . Its fruit body has been used as Chinese herb in treatment of various diseases. Recent in vivo studies have revealed that crude extracts of Antrodia camphorata can improve liver function, increase immunity and inhibit the growth of carcinoma. The objective of this research is to identify bioactive compounds from Antrodia camphorata’s mycelia with pharmaceutical effect on human liver cancer cells. We used high throughput method to screen and search for bioactive substances from the crude extract by employing human liver cancer cell based assay, instead of slow and expensive animal testing. At first, we were pleased to find that, when treating Hep 3B (a human liver cancer cell) with crude extracts of mycelia and fruit body of Antrodia camphorata for 48 hr, the IC50 values of 44.25 and 12.22 μg/mL were obtained, respectively. The crude extract of Antrodia camphorata was further fractionated (two times) on a silica gel column. These separated fractions (twelve fractions in total) were individually treated with Hep 3B cells. We found that the fraction 6 (F6) has salient bioactivity with a significant IC50 value of 6.4614 μg/mL. The active ingredient in F6 was purified by both HPLC and TLC and structurally identified by FAB MS, NMR and IR. The compound identified was 1-hydroxy-3-isobutyl-4-[4-(3-methyl-but-2-enyloxy)-phenyl]-pyrrole-2,5-dione (formula: C19H23NO4; molecular weight: 329.16). In the treatment of both Hep G2 and Hep 3B cells for 48 h, this compound gave the IC50 values of 9.903 and 6.388μg/mL, respectively.
Valkova, Simona Hristova. "Campaigning as a Spitzenkandidat: are lead candidates aligned with their party's manifesto?" Master's thesis, 2020. http://hdl.handle.net/10071/21031.
Повний текст джерелаAtualmente, o Twitter é uma das ferramentas online de eleição entre os atores políticos para fazerem campanha e estabelecerem uma ligação com os seus eleitorados, e o mesmo acontece com os "Spitzenkandidaten". O processo de "Spitzenkandidat", inicialmente implementado em 2014, tem sido um tema amplamente investigado. No entanto, com a personalização das campanhas a representar um dos principais fatores impulsionadores, é surpreendente ver a escassez de literatura sobre o assunto e, em particular, literatura relacionada com os principais candidatos na esfera do Twitter. Este estudo vem colmatar a lacuna na literatura académica ao responder à pergunta: "Até que ponto os Spitzenkandidaten de 2019 representaram os programas do seu partido através dos seus tweets ou desenvolveram campanhas individualizadas?". Os resultados revelam que os "Spitzenkandidaten" de 2019 não se centram na personalização como ferramenta principal no seu comportamento no Twitter. Além disso, o estudo demonstra de que forma fatores como a idade do candidato, a sua orientação partidária e se os candidatos fazem mais tweets ou retweets, têm influência no resultado.