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Marusyk, Andriy. "Decreased cellular fitness as a tumor promoter /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2006.
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Thesis (Ph.D. in Molecular Biology) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 124-145). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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SHARMA, NITESH DEVINARAYAN. "CHARACTERIZATION OF SOME MOLECULAR MECHANISMS ASSOCIATED TO CML PROGRESSION." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/63684.
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La Leucemia Mieloide Cronica(CML) è caratterizzata dalla presenza del gene di fusione BCRABL, prodotto dalla traslocazione tra i cromosomi 9 e 22. Se non trattata questa patologia progredisce entro 3 anni da una forma cronica(CP) a una forma acuta, la crisi blastica(BC). I meccanismi molecolari alla base della progressione della malattia non sono ancora completamente chiariti. Per raggiungere questo scopo ho quindi utilizzato un duplice approccio: 1)Grazie alla disponibilità di campioni CP/BC derivanti dagli stessi pazienti progrediti in BC dopo terapia standard, abbiamo sequenziato l’intero esoma(Whole Exome Sequencing-WES) e analizzato i dati utilizzando il campione CP come controllo. In questo modo l’analisi ha permesso di evidenziare solamente le alterazioni genetiche acquisite dopo progressione in BC. Ho quindi individuato la presenza di 2 mutazioni ricorrenti a carico dei geni RUNX1 e UBE2A, con quest’ultimo associato per la prima volta all’evoluzione in leucemia acuta e trovato mutato in circa l’11per cento dei campioni BC. Analisi successive invitro e invivo permetteranno di chiarire in particolare il ruolo delle mutazioni a carico di UBE2A nella progressione di CML. 2)Il secondo approccio si basa sullo studio del promotore del gene BCR. Dopo la traslocazione il gene di fusione BCRABL è sotto il controllo del promotore di BCR. Attualmente i meccanismi di regolazione di questo promotore sono poco chiari. Nel nostro laboratorio è stata precedentemente identificata una deregolazione trascrizonale di entrambi i geni BCR e BCRABL durante la progressione in BC. Ho quindi messo a punto un’analisi insilico per identificare i fattori di trascrizione che possano avere un ruolo nella regolazione del promotore BCR. Utilizzando tecniche di immunoprecipitazione di cromatina ho confermato in-vitro il legame dei fattori di trascrizione MYC e MAX a siti di legame specifici sul promotore di BCR(PBS1-4). Ho quindi osservato come l’overespressione di MYC e MAX sia in grado di indurre un aumento dell’espressione di BCR e di BCRABL, e che questo aumento risulta più evidente quando entrambi i fattori di trascrizione sono overespressi. Il silenziamento specifico di MYC nelle stesse linee cellulari ha dimostrato ulteriormente l’effetto regolatorio su entrambi i promotori. Per confermare questi risultati ho messo a punto un saggio di luciferasi inserendo il promotore di BCR nel plasmide pGL3. Cellule silenziate o meno per il gene MYC sono state poi trasfettate con i plasmidi di interesse. I risultati di questi esperimenti dimostrano l’importanza di MYC nella regolazione del promotore BCR. Ho inoltre osservato come il silenziamento di MYC in cellule BCRABL+ induca anche una alterazione del potenziale proliferativo e un aumento del tasso apoptotico. Questi dati descrivono quindi per la prima volta un meccanismo di regolazione del promotore BCR basato sul legame specifico di MYC e MAX e indicano una diretta associazione tra i livelli di espressione di MYC e quelli di BCRABL, entrambi upregolati durante l’evoluzione della malattia. E’ quindi suggerito un meccanismo molecolare alla base dell’aumento dell’espressione di BCRABL e dell’evoluzione in BC.Chronic Myeloid Leukemia (CML) is caused by the BCR/ABL fusion gene. If untreated CML progresses within 3 years from a mild and easy to control form, called chronic phase (CP), into an aggressive and deadly acute leukemia called blast crisis (BC). Despite the aggressiveness of BC and the poor overall survival of BC patients, little is known about the molecular mechanisms responsible for the progression of the disease. Therefore to gain insight into the molecular lesions responsible for BC, I used a two prong approach. First, I performed whole-exome SEQ analysis of paired CP/BC CML samples from patients that underwent progression to BC after standard therapy. By comparing exome-sequences of 11 paired CP (used as a control) and BC samples we found a total of 38 single nucleotide mutations occurring in BC and that were absent in the corresponding CP sample. By using this approach we found recurrent somatic single nucleotide mutations in RUNX1 and UBE2A in 2 out of 11 BC samples. UBE2A is here associated with CML progression for the first time. In addition, Copy Number Alteration analysis of 9 matched BC/CP exomes reveals the presence of large chromosomal alterations acquired during BC transformation, among which the bulky alteration of chromosome 7 in 3/9 BC samples. In conclusion, despite some heterogeneity in the genetic alterations identified in BC samples, we were able to find 2 recurrently mutated genes associated with blastic transformation RUNX1 and UBE2A, with the last one never been detected in CML samples. Ongoing analysis on additional BC/CP samples and in vitro experiments will help to clarify the role of UBE2A mutations in CML progression. The second approach involves the study of the BCR promoter. After the oncogenic translocation, the BCRABL gene is transcriptionally controlled by the BCR promoter. In spite of all the research performed in the field, little is known in the regulation of BCR promoter. We thus need to understand what are the transcription factors or the mechanisms that regulate BCRABL expression. By in-silico analysis and in-vitro Chromatin Immunoprecipitation experiments we found that COUP-TF1, CTCF, MYC and MAX proteins bind at BCR promoter at specific sites. As many studies have indicated the involvement of MYC in CML progression, we here focused the study on MYC and its co-factor MAX for our further analysis. In the present study we demonstrate that MYC_MAX heterocomplex binds to the BCR promoter at four different loci, leading to upregulation of BCR and BCRABL at both transcriptional and protein level. In contrast, silencing of MYC expression in various BCRABL positive cell lines causes significant downregulation of BCR and BCRABL, which consequently leads to decreased proliferation and induction of apoptosis. Taken together all these results demonstrate that MYC_MAX heterocomplex regulates BCR promoter basal activity and can contribute to BCRABL overexpression and blast aggressiveness of CML advanced phase.
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Elango, Rajula. "Break-induced replication repair pathway promotes mutagenesis and genomic instability in Saccharomyces cerevisiae." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5933.
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DNA double strand breaks can occur from various sources and the timely and accurate repair of these breaks is critical to maintain the genomic integrity of the cell. Break-induced replication (BIR) is a repair pathway that has been shown to repair DSBs where only one end of the break can locate homology, similar to ends seen at collapsed replication forks or eroded telomeres. BIR progresses by an unusual bubble-like intermediate. The asynchrony between the synthesis of leading and lagging strand synthesis during BIR leads to the accumulation of long single-stranded DNA (ssDNA) behind the bubble. This mechanism leads to the conservative inheritance of newly synthesized DNA. BIR repair can lead to increased mutations, loss of heterozygosity and gross chromosomal rearrangements. In this thesis I investigated the deleterious effects of the ssDNA formed during BIR. Using yeast, Saccharomyces cerevisiae, I showed that the regulation of Rad51 that binds ssDNA during BIR is important to prevent the accumulation of toxic joint intermediates. Here, I demonstrate that a known Rad51-interacting protein, Srs2, plays two key roles in counteracting the accumulation of lethal recombination intermediates. First, Srs2 dislodges Rad51 from long ssDNA formed during DSB repair and therefore prevents promiscuous strand invasions that generate lethal joint molecules. Second, Srs2 helicase dismantles toxic intermediates that have already formed. We also demonstrate that the structure-specific endonucleases, Mus81 and Yen1, can resolve toxic joint molecules formed in the absence of Srs2, thus promoting cell survival.
The other goal of this thesis was to study the effects of ssDNA accumulated during BIR in the formation of base-substitution mutagenesis. I test whether this ssDNA is mutagenic by analyzing BIR with and without the presence of DNA damaging agents, including methyl methanesulfonate (MMS) and APOBEC3A. I observed a hypermutagenic effect of BIR with respect to base- substitutions in both cases. Importantly, BIR synergizes with ssDNA damaging agents to produce mutation clusters similar to those previously observed in cancer. I also report the critical role translesion polymerase Polζ plays in the formation of base-substitutions resulting from BIR. Finally, I have discovered a completely novel, UNG1-dependent mechanism of supposed error-free bypasses of APOBEC-induced DNA lesions during BIR that promotes chromosomal rearrangements.
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Li, Frank. "Analysis of the Effects of BCL-2 Promoter G-Quadruplex Formation on Protein Expression." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/244406.
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Bcl-2 is an anti-apoptotic protein that has been implicated in a number of human diseases, including some cancers. Within the P1 promoter region, which is involved in 80-90% of bcl-2 transcriptional control, a G-rich region (Pu39) can form various monomeric G-quadruplex folding structures, each with four of the six runs of multiple guanines present. The midG4 and 5'5G4 structures have been found to be the most stable and are the potential targets of comparative studies on transcriptional effects. Plasmids containing a luciferase reporter gene under the control of this bcl-2 P1 promoter region, along with mutants to alter or eliminate G-quadruplex formation, were constructed in order to study the ability of Pu39 to control transcription. Initial luciferase assay results in HeLa and HEK293 cells suggest that mutants designed to isolate certain G-quadruplex structures caused an overall decrease in protein expression while mutants designed to knock out major folding structures caused an increase in protein expression. DNA mutant constructs in conjunction with quadruplex-specific, quadruplex-interacting drugs appear to consistently decrease protein activity, supporting the idea that the G-quadruplex has an inhibitory effect on transcription.
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DUGRAY, AYMERIC. "Controle de l'hematopoiese maligne a l'aide de retrovirus a promoteurs inductibles : modele de leucemogenese par bcr-abl." Paris 7, 2001. http://www.theses.fr/2001PA077133.
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Les phenomenes moleculaires qui sont responsables de la progression du clone leucemique ph1 vers la phase blastique au cours de la leucemie myeloide chronique sont indetermines. Ce travail a consiste a modeliser un des aspects phenotypiques de cette progression qui consiste en l'augmentation de l'expression de bcr-abl. Dans ce but, nous avons genere un modele de leucemogenese a l'aide d'un systeme retroviral a promoteur inductible gouvernant l'expression du gene bcr-abl. Ce retrovirus inductible a permis la transduction de la lignee hematopoietique ba/f3 avec obtention de clones uniques dans lesquels l'expression de bcr-abl peut etre modulee par l'ajout de tetracycline dans le milieu. La fonctionnalite du systeme inductible a pu etre testee avec succes dans les experiences de transformation et/ou de tumorigenicite in vivo. Les outils inductibles generes, ainsi que les modeles in vitro disponibles dans le laboratoire, nous ont par la suite permis de demontrer la responsabilite directe de bcr-abl dans la degradation proteasome-dependante de dna-pkcs, proteine de reparation majeure des cassures double-brin. Cet evenement moleculaire pourrait etre un phenomene clef responsable de l'instabilite genetique favorisant ainsi la progression du clone ph1 vers la crise blastique. Enfin, ce modele inductible nous a permis de realiser une etude plus large des effets de l'expression de bcr-abl grace a l'utilisation de la methode de puces a adn. Nous avons ainsi mis en evidence l'induction de l'expression de plusieurs genes, notamment valosin-containing protein, (vcp) et de cis1/socs1, intervenant respectivement dans la reparation de l'adn et dans la regulation negative de la voie jak/stat. La relevance de ces anomalies d'expression a ete testee dans des modeles de leucemies in vitro ainsi que dans les cellules primaires de patients atteints de lmc. La demonstration de leur role dans la leucemogenese induite par bcr-abl necessitera des experiences futures de surexpression ou d'inhibition.
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Rodríguez, José M. "Bcl-2 related ovarian killer, Bok, is cell cycle regulated and sensitizes to stress-induced apoptosis." Scholar Commons, 2007. http://scholarcommons.usf.edu/etd/2342.
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Bok/Mtd (Bcl-2-related ovarian killer/Matador) is considered a pro-apoptotic member of the Bcl-2 family. Though identified in 1997, little is known about its biological role. We have previously demonstrated that Bok mRNA is upregulated following E2F1 over-expression. In the current work, we demonstrate that Bok RNA is low in quiescent cells and rises upon serum stimulation. To determine the mechanism underlying this regulation, we cloned and characterized the mouse Bok promoter. We find that the mouse promoter contains a conserved E2F binding site (-43 to -49) and that a Bok promoter-driven luciferase reporter is activated by serum stimulation dependent on this site. Chromatin immunoprecipitation assays demonstrate that endogenous E2F1 and E2F3 associate with the Bok promoter in vivo. Surprisingly, we find that H1299 cells can stably express high levels of exogenous Bok. However, these cells are highly sensitive to chemotherapeutic drug treatment. Taken together these results demonstrate that Bok represents a cell cycle-regulated pro-apoptotic member of the Bcl-2 family, which may predispose growing cells to chemotherapeutic treatment.
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Checkett, Jane Melinda. "Development of a micro-scale microtransfection technique exploiting reporter gene systems to analyse bcl-2 family promoter activity." Thesis, Keele University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325826.
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Ogunnowo-Bada, Emmanuel Oluwatobi. "The role of brain glucokinase and Bcl-2-associated death promoter in the control of blood glucose homeostasis." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648754.
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Abomoelak, Bassam. "Développement et immunogénicité de souches recombinantes de BCG produisant des antigènes bactériens chimériques." Lille 1, 1997. http://www.theses.fr/1997LIL10220.
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Deux souches recombinantes de bcg exprimant une fusion protéique entre s1, la sous-unité enzymatique de la toxine pertussique et le tetc, le fragment cc de la toxine tétanique ont été développées sous deux promoteurs différents (85a, hsp60). L'immunisation des souris avec la première souche n'a pas induit de réponse immunitaire, tandis que l'immunisation des souris avec la deuxième souche a induit une réponse immunitaire humorale et cellulaire. Une autre souche recombinante de bcg capable d'exprimer une fusion protéique entre s1, tetc et le fragment b de la toxine diphtérique a été développée.
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Tollin, Craig Jeffrey. "The characterization of Clostridium beijerinckii NRRL B592 cells transformed with plasmids containing the butanol-production genes under the control of constitutive promoters." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/77235.
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Clostridium beijerinckii is a spore-forming, obligate anaerobe that is capable of producing butanol, acetone and isopropanol. These industrial chemicals are traditionally known as solvents. The regulation of solventogenic fermentation is linked to the onset of sporulation, so that by the time the organism begins to produce solvents, it is also entering into spore formation and metabolic slowdown. The goal of this research project was to study the effect of placing the solvent-production genes from C. beijerinckii under the control of constitutive promoters from other genes, in an attempt to allow an earlier start of butanol production during the growth phase than is the case with the wild-type cells.
The aldehyde dehydrogenase from C. beijerinckii NRRL B593 (ald) and alcohol dehydrogenase from C. beijerinckii NRRL B592 (adhA) were placed under the control of the promoter from the acid-producing operon (the BCS operon) in one vector, and under the control of the promoter from the ferredoxin gene in another. In both cases, aldehyde dehydrogenase activity was produced earlier in the growth phase in transformed cells, but alcohol dehydrogenase activity was not.
The adhA gene from C. beijerinckii NRRL B592 was paired with the adhB gene from the same organism in a third vector, both under the control of the promoter from the BCS operon. In cells transformed with this vector, alcohol dehydrogenase activity was observed earlier in the growth phase than it was in wild-type NRRL B592 cells.Ph. D.
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RAMBAL, ANILA. "ROLE OF BCL-2 FAMILY MEMBERS TO PROMOTE GLUCOCORTICOID –INDUCED APOPTOSIS BY MEK INHIBITORS IN LEUKEMIC CELLS." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1790.
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Glucocorticoids (GC) are common components of many chemotherapeutic regimens for lymphoid malignancies. GC-induced apoptosis involves an intrinsic BCL-2 family-regulated pathway. It has been shown that BIM (BCL-2 interacting mediator of cell death), a BH3-only pro-apoptotic protein, is up-regulated by dexamethasone (Dex) treatment in acute lymphoblastic leukemia (ALL) cells. Furthermore, BIM is inactivated by extracellular signal-regulated kinase (ERK)-mediated phosphorylation. We therefore hypothesized co-treatment with Dex and MEK/ERK inhibitors would promote apoptosis in ALL cells through BIM up-regulation and activation. We show here that a MEK inhibitor, PD184352 synergistically enhances Dex lethality in CCRF-CEM (T-ALL) cells. Co-treatment with Dex and PD184352 results in BIM accumulation. Down-regulation of BIM by short-hairpin RNA in CCRF-CEM cells suppressed apoptosis by Dex/PD184352 co-treatment. In contrast, another BH3-only protein, BAD is dispensable. Thus, BIM is a critical molecule in this regimen, and targeting BIM by drugs combination could be effective on ALL and possibly other malignancies.
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Zhou, Jia. "Dna Glycosylases Remove Oxidized Base Damages From G-Quadruplex Dna Structures." ScholarWorks @ UVM, 2015. http://scholarworks.uvm.edu/graddis/529.
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The G-quadruplex DNA is a four-stranded DNA structure that is highly susceptible to oxidation due to its G-rich sequence and its structure. Oxidative DNA base damages can be mutagenic or lethal to cells if they are left unrepaired. The base excision repair (BER) pathway is the predominant pathway for repair of oxidized DNA bases. DNA glycosylases are the first enzymes in BER and are responsible for removing base lesions from DNA. How DNA glycosylases remove base lesions from duplex and single-stranded DNA has been intensively studied, while how they act on G-quadruplex DNA remains to be explored.
In Chapter II of this dissertation, we studied the glycosylase activity of the five mammalian DNA glycosylases (OGG1, NTH1, NEIL1, NEIL2 and mouse Neil3) on G-quadruplex DNA formed by telomere sequences that contain a single base lesion. We found that telomeric sequences that contain thymine glycol (Tg), 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh) or spiroiminodihydantoin (Sp) all formed the basket form of an antiparallel G-quadruplex DNA structure in Na+ solution. We also showed that no glycosylase was able to remove 8-oxoG from quadruplex DNA, while its further oxidation products, Sp and Gh, were good substrates for mNeil3 and NEIL1 in quadruplex DNA. In addition, mNeil3 is the only enzyme that removes Tg from quadruplex DNA and the glycosylase strongly prefers Tg in the telomere sequence context in both single-stranded and double-stranded DNA.
In Chapter III, we extended our study to telomeric G-quadruplex DNA in K+ solution and we also studied quadruplex DNA formed by promoter sequences. We found that 8-oxoG, Gh and Sp reduce the thermostability and alter the folding of telomeric quadruplex DNA in a location-dependent manner. Also, the NEIL1 and NEIL3 DNA glycosylases are able to remove hydantoin lesions but none of the glycosylases, including OGG1, are able to remove 8-oxoG from telomeric quadruplex DNA in K+ solution. Interestingly, NEIL1 or NEIL3 do not efficiently remove hydantoin lesions at the site that is most prone to oxidation in quadruplex DNA. However, hydantoin lesions at the same site in quadruplex DNA are removed much more rapidly by NEIL1, NEIL2 and NEIL3, when an extra telomere TTAGGG repeat is added to the commonly studied four-repeat quadruplex DNA to make it a five-repeat telomere quadruplex DNA. We also show that APE1 cleaves furan in selected positions in Na+-coordinated telomeric quadruplex DNA structures. We use promoter sequences of the VEGF and c-MYC genes as models to study promoter G-quadruplex DNA structures, and show that the NEIL glycosylases primarily remove Gh from Na+-coordinated antiparallel quadruplex DNA but not from K+-coordinated parallel quadruplex DNA containing VEGF or c-MYC promoter sequences.
Taken together, our data show that the NEIL DNA glycosylases may be involved in both telomere maintenance and gene regulation.
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Chan, Jessica Zee. "Stereoselective Functionalization of Carbonyl Compounds and N-Alkylamines Promoted by Cooperative Catalysts:." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108940.
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Thesis advisor: Masayuki WasaThis dissertation describes the development of cooperative catalyst systems for the functionalization of monocarbonyl compounds and stereoselective transformations of alpha-C–H bonds of N-alkylamines, inspired by the concepts of frustrated Lewis pairs (FLPs). Prior to this dissertation research, practical and broadly applicable C–C and C–heteroatom bond forming reactions involving the FLP complexes that provide synthetically desirable products with high enantioselectivity remained to be developed. Chapter 1 of this dissertation describes the recent advances in the transformations involving FLPs and B(C₆F₅)₃-catalyzed reactions. Inspired by the unique capability of FLP catalysts to activate otherwise unreactive molecules, and circumvent undesirable acid–base complexation, we have developed potent cooperative acid/base catalysts for C–C bond forming reactions of various monocarbonyl compounds and an appropriate electrophile, which will be discussed in Chapter 2. Another reactivity of FLPs to be explored has to do with the catalytic and enantioselective reactions of N-alkylamines, where two Lewis acid catalysts with potentially overlapping functions, work cooperatively to activate alpha-amino C–H bonds and promote the enantioselective C–C bond forming reaction between N-alkylamines and a nucleophilic species. In Chapter 3, B(C₆F₅)₃-catalyzed union of N-alkylamines and silicon enolates followed by the enantioselective B(C₆F₅)₃/Mg–PyBOX-catalyzed alpha-alkylation of N-alkylamines and alpha,beta-unsaturated compounds to form beta-amino carbonyl compounds will be described. In Chapter 4, B(C₆F₅)₃/Cu–PyBOX-catalyzed alpha-C–H alkynylation of N-alkylamines and the applications in late-stage functionalization and stereoselective synthesis will be discussed
Thesis (PhD) — Boston College, 2020
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Rwimo, Edward John. "How solidarity as a virtue can promote better living conditions in Tanzania." Thesis, Boston College, 2015. http://hdl.handle.net/2345/bc-ir:105021.
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Kim, Minsong. "Being Connected: How a Relational Network of Educators Promotes Productive Communities of Practice." Thesis, Boston College, 2016. http://hdl.handle.net/2345/bc-ir:107270.
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Thesis advisor: Larry LudlowIn this dissertation study, I examined the extent to which a relational network of teachers, administrators, two-way immersion (TWI) experts and mentors promote productive communities of practice (CoP). In a conventional instruction, teachers are often isolated in their classrooms, and a private practice culture prevails. In 2012, the Two-Way Immersion Network for Catholic Schools (TWIN-CS) was launched in an effort to support school reform by engaging school leaders and teachers to collectively learn toward implementing TWI models in their schools. Using the framework of communities of practice (Lave & Wenger, 1991; Wenger, 1999), I employed a case study design (Yin, 2009) to explore a national network of Catholic elementary school educators. Data sources included qualitative data featuring semi-structured interviews and quantitative source from a relational network survey. Qualitative results revealed that organizational features of TWIN-CS are critical in promoting participants’ learning to implement TWI. In particular, participants discussed the annual TWIN Summer Academy and bi-monthly webinars to be instrumental for their learning. Many participants also shared that an expansion of CoPs beyond TWIN-CS further prompted productive learning. However, the qualitative evidence also showed a lack of clear internal and external network structures and role definition, and sustaining connection beyond the Summer Academy and webinars were perceived as a great challenge. Quantitative results suggest that TWIN-CS has a core-and-periphery network structure with the Boston College design team at the innermost core, with visibly dense ties connecting to and from them. Most teachers, on the other hand, occupy the most peripheral positions in this network. Survey evidence also showed that participants generally perceived a much stronger learning relationship within schools and showed less certainty on cross-network relationships. In terms of learning characteristics, majority of the respondents viewed knowledge sharing, trust, and advice-oriented dimensions “strongly” but perceived a lack of data-driven learning for both within school and cross-network. I conclude this study with a discussion of implications for future research and practice
Thesis (PhD) — Boston College, 2016
Submitted to: Boston College. Lynch School of Education
Discipline: Educational Research, Measurement and Evaluation
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Nascimento, Larissa Vilela. "Estudo comparativo de promotores de micobactérias utilizando GFP como gene repórter para o desenvolvimento de vacinas de BCG recombinante." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-23112015-191124/.
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BCG é uma das vacinas mais usadas no mundo. Avanços na manipulação genética têm permitido o seu uso como carreador de antígenos heterólogos, porém o aprimoramento dos sistemas de expressão se faz necessário, sendo o promotor um importante elemento, uma vez que regula o nível de produção do antígeno, induzindo uma resposta imunológica adequada. Avaliamos a atividade de diferentes promotores de micobactérias, como o PAg, PAN, PBlaF*, Phsp60 e um promotor ainda não caracterizado do micobacteriófago L5, usando o gene gfp como repórter da expressão, todos clonados no vetor extracromossomal, pLA71. Foi possível avaliar as cepas de M. smegmatis e BCG fluorescentes para quase todas as construções e alguns plasmídeos pLA71-p mostraram características diferentes dependentes da micobactéria transformada. Numa escala de força de expressão, os diferentes promotores se apresentaram como fraco (pLA71-PAN-gfp), médio (pLA71-PBlaf*-gfp) e forte (pLA71-Phsp60-gfp). Os rBCG foram usados para infecção de macrófagos e a atividade dos promotores não foi afetada após a internalização. Para ensaio de localização, camundongos foram inoculados com BCG e foi possível confirmar a presença de colônias (recombinantes ou não) nos pulmões após 1 e 3 dias de inoculação, por plaqueamento em meio sólido e por microscopia confocal.BCG is one of the most widely used vaccines in the world. Advances in genetic manipulation have allowed their use as a carrier for heterologous antigens, however the improvement of systems of expression is necessary, the promoter being an important element, since it regulates the expression level of the antigen, inducing an adequate immune response. We evaluated the activity of different promoters of mycobacteria, such as PAg, PAN, PBlaF* and Phsp60, and the not yet characterized promoter of the micobacteriophage L5, using GFP as a reporter gene expression activity, all cloned in the extrachromosomal vector, pLA71. It was possible to evaluate promoters in the M. smegmatis and BCG strains, fluorescent for almost all constructions and some pLA71-p plasmids showed different characteristics dependent on the transformed mycobacterium. The different promoters showed expression levels as weak (pLA71-PAN-gfp), medium (pLA71-PBlaf*-gfp) and strong (pLA71-Phsp60-gfp). The rBCG were used for infection of macrophages and the activity of the promoters wasnt affected after internalization. For BCG location test, mice were inoculated and it was possible to confirm the presence of colonies (recombinant or not) in the lungs after 1 and 3 days after inoculation by plating on solid medium and by confocal microscopy.
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Wang, Rayna. "Exemplary practices that affirm and promote cultural and linguistic diversity in head start classrooms." Thesis, Boston College, 2017. http://hdl.handle.net/2345/bc-ir:107433.
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Thesis advisor: Mariela PaezWith the continued growth of culturally and linguistically diverse (CLD) students, it is necessary for teachers to be intentional about serving students whose backgrounds are assets but nonetheless different from the dominant culture and language in American society. Because most research on teaching practices has focused on the academic development of children in preschool, this study tries to fill a gap in the literature by examining teaching practices that respond to and affirm cultural diversity. After conducting interviews and observations in three Head Start classrooms, four core teacher beliefs (reciprocal relationships with family, importance of home language, social emotional emphasis, and inclusion of culture) were identified across the sites; these beliefs impacted how teachers created a multicultural space and tailored instruction for students. The findings contribute to the field by providing insight for how teachers can continue to foster inclusive classrooms that value and celebrate children’s unique identities
Thesis (BA) — Boston College, 2017
Discipline: Departmental Honors
Discipline: Education
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Uhl, Elizabeth. ""Work Hard and Be Kind”: How a Sports Team’s Shared Values Promote Social Movement Engagement." Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109149.
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Thesis advisor: Lyndon GarrettCoinciding with the upsurgence of the Black Lives Matter Movement in the Summer of 2020, collegiate and professional sports teams have exhibited increased involvement in social issues. Existing research primarily analyzes the platform and visibility that athletes have to promote social agendas, but there is a gap in knowledge regarding how a sports team forms a collective identity around a social movement. This study seeks to fill this gap in research by utilizing qualitative surveying and interviewing to examine how Boston College athletes engage in the Black Lives Matter Movement. Processes of grounded theory and inductive analysis are used to understand how the Boston College Women’s Rowing Team values contribute to the team’s shared mental model to fulfill the conditions of social movement emergence and further promote team value adoption and team success. Evaluation of student-athletes across different Boston College teams through this study also offers insights to the controversy over sports teams engaging in social issues
Thesis (BA) — Boston College, 2021
Submitted to: Boston College. College of Arts and Sciences
Discipline: Departmental Honors
Discipline: Sociology
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Jang, Hwanjong. "Efficient and Selective Synthesis of Multifunctional Organoboron Compounds Promoted by Cu-Based N-Heterocyclic Carbene Complexes." Thesis, Boston College, 2016. http://hdl.handle.net/2345/bc-ir:107188.
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Thesis advisor: Amir H. HoveydaChapter 1. We have developed a single-vessel catalytic protocol for double protoboryl additions to terminal alkynes with B2(pin)2 promoted by Cu complex derived from chiral N-heterocyclic carbene (NHC), to achieve enantiomerically enriched versatile vicinal diborons. Since an alkenyl(pinacolato)boron, which was in situ generated by the first protoboration of a terminal alkyne, can serve as an effective substrate for the second protoboration (alkenylboron can allow delocalization of π electrons of olefin to a partially vacant p orbital on boron), single-vessel catalytic process with 2 equiv. of B2(pin)2 in the presence of sulfonate-bearing chiral NHC–Cu complex, affords enantiomerically enriched 1,2-diborons in up to 93% yield and 97.5:2.5 enantiomeric ratio (e.r.). Site-selective Pd-catalyzed cross-coupling with alkenyl bromide shows the versatility of the resulting diboron compounds, which delivers the coupling product efficiently. Interestingly, only the less hindered, primary C–B bond on vicinal diboron compound participates in the cross coupling. Chapter 2. Cu-catalyzed protocol for selective formation of α-alkenylborons has been demonstrated. With achiral NHC–Cu complex, readily prepared from commercially available imidazolinium salt, various terminal alkynes are converted to internal alkenylborons in up to 93% yield with high to exclusive α selectivity. Propargyl ethers, amides and aryl alkynes are proved to be suitable substrates. Utility of α-alkenylborons is demonstrated by conversion to methyl ketone and synthesis of cyclic alkenylboron compound. In addition, when Cu complex bearing a stronger electron-donating NHC is used, the site selectivity of protoboration reaction becomes reversed, which delivers the alternative isomer, β-alkenylboron efficiently. By altering the steric and electronic nature of NHC, site selectivity is dramatically changed. Mechanistic basis for site selectivity is presented. Chapter 3. Efficient and selective protocol for synthesis of enantiomerically enriched silylborons is described. In the presence of achiral NHC–Cu complex, site- and stereoselective protosilyl additions to terminal alkynes afford a wide range of alkyl- and aryl-substituted (E)-β-alkenylsilanes. Chiral monodentate NHC−Cu complex promotes enantioselective protoboration of alkyl- or alkenyl-bearing alkenylsilanes, delivering vicinal borosilanes with up to 96.5:3.5 e.r. When an alkene bearing both silyl and aryl groups is utilized, on the other hand, geminal silylboron is obtained with high enantio- (93:7–98.5:1.5 e.r.) and site selectivity (up to >98% geminal). In this case, we have reasoned that the electronic attribute of aryl unit is more dominant than the silyl group to control site selectivity. To demonstrate the utility of the Cu-catalyzed transformation, we have illustrated the formal synthesis of bruguierol A, natural product active against Gram-positive and also Gram-negative bacteria. The key intermediate geminal borosilane is provided by sequential NHC–Cu-catalyzed protosilylation and protoboration of terminal alkyne in 77% overall yield with 97.5:2.5 e.r. and 97% site selectivity. Additionally, stereochemical models to account for levels and trends in site- and enantioselectivity are proposed. Chapter 4. New methods for enantioselective protonation of 2-B(pin)-bearing allylcopper, which is in situ generated by site-selective Cu–B addition to 1,1-disubstituted allene, are presented. Transformations are promoted by a chiral NHC–Cu complex, affording an alkenylboron containing α-carbon stereogenic center. Enantiomerically enriched aryl-, heteroaryl- and silyl-bearing alkenylborons are generated in high yield (up to 98%) and selectivities (up to >98% site selectivity and 96.5:3.5 e.r.). To explore the utility of enantiomerically enriched alkenylborons, we have developed Cu-catalyzed enantioselective allylic alkenyl addition to allylic phosphate. A chiral NHC–Cu complex promotes the allylic substitution of enantiomerically enriched alkenylboronic acid with ally phosphate to deliver 1,4-diene in 62% yield with 96:4 d.r. (>98% stereoselectivity). Chapter 5. We have developed a single-vessel, multicomponent process to synthesize N-bearing quaternary carbon stereogenic centers with exceptional diastereo- (>98:2 d.r. for all cases) and high enantioselectivity (88:12 to >99:1 e.r. except one case). Especially, protecting group-free ketoimine (“N–H” ketoimine), which can be prepared by alkylation of a readily available nitrile, has been utilized for the study. The transformation of “N–H” ketoimine is very useful because the obtained amine has no protecting group, which allows us to avoid the deprotection step as well as to be able to choose appropriate protecting group for subsequent chemical reactions. By oxidation of α-tertiary carbamine with NaBO3, β-amino ketones (Mannich reaction product) are obtained in up to 83% yield. A stereochemical model to account for the level of diastereo- and enantioselectivity are presented using DFT calculations. To show the utility of the present method, we have synthesized a medicinally active compound, which was studied for Alzheimer’s disease. The Cu-catalyzed protocol delivers the core structure of the target molecule with exclusive diastereo- and enantioselectivity (>98:2 d.r. and 99.5:0.5 e.r.)
Thesis (PhD) — Boston College, 2016
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Cao, Min. "Enantioselective Transformations Promoted by Cooperative Functions of an Achiral Lewis Acid and a Chiral Lewis Acid:." Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109203.
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Thesis advisor: Masayuki WasaThesis advisor: Amir H. Hoveyda
This dissertation describes the development of cooperative catalyst systems that contain an achiral Lewis acid and a chiral Lewis acid that may have overlapping functions but play their independent roles to promote enantioselective C–C bond formations. Chapter 1 provides a summary of recent advances made in the field of enantioselective cooperative catalysis that served as intellectual foundations for this dissertation research. As it will be discussed in the first chapter, key limitations of cooperative catalysis are: (1) undesirable catalyst deactivation which occurs due to acid/base complexation, (2) requirement for base sensitive pronucleophiles and acid sensitive electrophiles, and (3) poor reaction efficiency. In an effort to overcome these fundamental limitations, we have developed “frustrated” Lewis pair (FLP)-based catalyst systems that consist of potent and sterically encumbered Lewis acids used in pair with bulky N-containing Lewis bases. To demonstrate the potential of the novel FLP catalyst system, we describe our work involving the enantioselective Conia-ene-type cyclization (Chapter 2). In the subsequent chapter (Chapter 3), we discuss the application of the FLP catalysts for enantioselective β-amino C–H functionalization reactions
Thesis (PhD) — Boston College, 2021
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Lebeko, Maribanyana R. "Construction, stability and immunogenicity of recombinant BCG expressing HIV-1 subtype C gag under the control of MtrA promoter, with or without the leader sequences." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10586.
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This study aimed to compare recombinant mycobacteria expressing HIV-1 gag under the control of different promoters and leader sequences. This was done to determine whether the genetic stability of the recombinant mycobacteria could be improved by modification of these vector features and to gain insight into what types of immune responses may be elicited in mice.
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Shi, Ying. "Copper-catalyzed Enantioselective Allylic Substitutions and Conjugate Additions Promoted by Chiral Sulfonate- or Alkoxy-containing N-heterocyclic Carbenes." Thesis, Boston College, 2017. http://hdl.handle.net/2345/bc-ir:107648.
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Thesis advisor: Amir H. HoveydaChapter 1. A Review of Sulfonate-Containing NHC Ligands in Copper-Catalyzed Enantioselective Transformations—Maneuvering Selectivities in Tight Space. A comprehensive review of enantioselective copper-catalyzed transformations, which are promoted by a chiral N-heterocyclic carbene metal complex that features a unique sulfonate motif, is provided in this chapter. Reactions have been categorized into four sets: allylic substitutions conjugate additions, Cu-B additions alkenes and multicomponent reactions. The mechanistic scenarios provided by DFT calculations accounts for their uniquely reaction profile in enantioselective allylic substitutions (EAS), enantioselective conjugate additions (EAS) and enantioselective Cu-B additions to alkenes. Mechanistic investigations (density functional theory calculations and deuterium labeling) point to a bridging function for an alkali metal cation connecting the sulfonate anion and a substrate’ s phosphate group to form the branched addition products as the dominant isomers via Cu(III) π -allyl intermediate complexes in EAS reactions. Sulfonate-bearing NHC ligand with different substitution patterns promote EAS reactions with different reactivity and enantioselectivity. We also developed a guideline to follow to choose the proper sulfonate-based NHC ligands according to the combination of the substrates and the nucleophiles. Chapter 2. NHC–Cu-Catalyzed Enantioselective Allylic Substitutions with Silyl-protected Propargyl Boron Reagent to Generate Tertiary and Quaternary Carbon Stereogenic Centers. Catalytic allylic substitution reactions involving a propargylic nucleophilic component are presented; reactions are facilitated by 5.0 mol % of a catalyst derived from a chiral N-heterocyclic carbene (NHC) and a copper chloride salt. A silyl-containing propargylic organoboron compound, easily prepared in multi-gram quantities, serves as the reagent. Aryl- and heteroaryl-substituted disubstituted alkenes within allylic phosphates and those with an alkyl or a silyl group can be used. Functional groups typically sensitive to hard nucleophilic reagents are tolerated, particularly in the additions to disubstituted alkenes. Reactions may be performed on the corresponding trisubstituted alkenes, affording quaternary carbon stereogenic centers. Incorporation of the propargylic group is generally favored (vs allenyl addition; 89:11 to >98:2 selectivity); 1,5-enynes can be isolated in 75−90% yield, 87:13 to >98:2 SN2′:SN2 (branched/linear) selectivity and 83:17−99:1 enantiomeric ratio. Utility is showcased by conversion of the alkynyl group to other useful functional units. Application to stereoselective synthesis of the acyclic portion of antifungal agent plakinic acid A, containing two remotely positioned stereogenic centers, by sequential use of two different NHC–Cu-catalyzed enantioselective allylic substitution (EAS) reactions further highlights utility. Chapter 3. NHC–Cu-Catalyzed Enantioselective Allylic Substitutions with Methylenediboron to Generate Tertiary and Quaternary Carbon Stereogenic Centers. A catalytic EAS method for the site- and enantioselective addition of commercially available di-B(pin)-methane to disubstituted allylic phosphates is introduced. Transformations are facilitated by a sulfonate-containing NHC–Cu complex and products are obtained in 63–95% yield, 88:12 to >98:2 SN2’/SN2 selectivity, and 85:15–99:1 enantiomeric ratio. The utility of the approach is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A, in an all-catalytic-method synthesis route. Catalytic EAS methods of the di-B(pin) methane to Z-trisubstituted allylic phosphates are also disclosed and DFT calculations provide insights to the stereochemical models for those transformations and rationales for the choice of Z-trisubstituted allylic phosphates as the starting materials. Chapter 4. Enantioselective NHC–Cu-Catalyzed Prenyl Conjugate Additions to Enoates to Generate Tertiary Carbon Stereogenic Centers. An efficient catalytic protocol for generation of prenyl-bearing tertiary carbon stereogenic centers from aryl-substituted enoates was achieved in the presence of a chiral alkoxy-based NHC–Cu complex. A range of aryl and heteroaryl-substituted substrate were suitable substrates, the corresponding prenyl conjugate addition products were generated in up to 94% yield and 95:5 enantioselectivity. The utility of the current method has been shown in the application to the synthesis of a selective integrin antagonist. DFT calculations provided a stereochemical model for the ECA reaction employing alkoxy-containing NHC–Cu catalyst
Thesis (PhD) — Boston College, 2017
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Rodríguez, José M. "Bcl-2 related ovarian killer, Bok, is cell cycle regulated and sensitizes to stress-induced apoptosis." [Tampa, Fla.] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002146.
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Dunn, Lori Ann Compagnone. "Using Elements of a Screenplay to Promote Visualization and Increase Reading Comprehension in Students With Disabilities and Striving Readers:." Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109097.
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Thesis advisor: David ScanlonImproving reading comprehension for middle school students with disabilities and others who struggle with reading, referred to here as striving readers, is challenging. Formal reading instruction typically shifts from skills acquisition to application in middle and high school, providing inadequate support in the skills for comprehension (Chall, 1983; Klingner et al., 2007). Further, both students with disabilities and striving readers can have negative school experiences which impact their reader identities and cause them to become disengaged from learning. It is increasingly challenging for secondary teachers to provide interventions which explicitly teach and reinforce critical comprehension skills while sustaining student engagement. An experimental screenplay intervention designed by the researcher to increase visualization and promote reading comprehension was used. The intervention was based on research by Snyder (2005) identifying elements of a screenplay, similar to story grammar. Movies were used first as a novel way to engage learners; visual supports were gradually reduced as students transferred visualizing skills to texts of increasing complexity. The readers used plot diagrams to organize the elements graphically in support of their comprehension. Seven middle school students with high incidence disabilities and striving readers learned to identify seven elements of a screenplay in a 3-week online researcher-developed intervention. A mixed-methods case study design was used to identify reading-related outcomes and students’ experiences (attitudes and behaviors) of reading as they learned the intervention. Data were collected for reading comprehension, recognition of screenplay elements, and visualization skills. Reading behaviors, attitudes, identities, and motivation for reading were also assessed. Findings revealed whole-class mean score gains in passage and sentence level comprehension, pre-to-post. Students also learned the screenplay elements and were proficient in finding examples within a text. Further, the students reported greater details at post-test when reporting their visualizations and when describing elements. Case studies of three students representing three reading proficiency levels upon entrance to the study revealed distinct experiences for each. Implications for reading instruction are discussed
Thesis (PhD) — Boston College, 2021
Submitted to: Boston College. Lynch School of Education
Discipline: Teacher Education, Special Education, Curriculum and Instruction
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Gao, Fang. "Copper-Catalyzed Enantioselective Allylic Substitution Reactions with Organoaluminum and Boron Based Reagents Promoted by Chiral Sulfonate Bearing N-Heterocyclic Carbenes." Thesis, Boston College, 2013. http://hdl.handle.net/2345/bc-ir:101227.
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Thesis advisor: Amir H. HoveydaChapter 1. A Review of Catalytic Enantioselective Allylic Substitution (EAS) with Chiral Sulfonate Containing N-heterocyclic Carbenes (NHC). A comprehensive review of enantioselective allylic substitution reactions, which are promoted by a chiral N-heterocyclic carbene metal complex that features a unique sulfonate motif, is provided in this chapter. Reactions are classified into two categories. One class of transformations is catalyzed by a series of easily modifiable sulfonate bearing NHC-Cu complexes, with which a range of nucleophilic organometallic reagents (i.e., organozinc-, aluminum-, magnesium- and boron-based) that carry different carbon-based units are readily utilized in efficient and highly selective C-C bond forming processes. Another set of reactions exclude the use of a copper salt; catalytic amount of a sulfonate containing imidazolinium salt is capable of promoting additions of alkyl Grignard, zinc and aluminum species to easily available allylic electrophiles in a site- and enantioselective fashion. The mechanistic scenarios of both catalytic systems that account for the observed experimental data are discussed in detail. Chapter 2. Cu-Catalyzed Enantioselective Allylic Substitutions with Aryl- and Heteroarylaluminum Reagents. In this chapter, the first examples of EAS reactions of aryl- and heteroaryl-substituted dialkylaluminum reagents to a wide range of trisubstituted allylic phosphates are demonstrated through a facile and selective catalysis rendered possible by an in situ generated sulfonate containing NHC-Cu complex, delivering enantiomerically enriched olefin products that bear an all carbon quaternary stereogenic center. The requisite organometallic species are easily prepared from either the corresponding aryl- and heteroaryl halides, or through efficient and site selective deprotonation at the C-2 position of furan and thiophene; such aluminum entities are readily used in situ without the requirement of purification. Application to small molecule natural product synthesis is also carried out to illustrate the utility of the present protocol. Chapter 3. Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylaluminum Reagents. This chapter focuses on our research towards construction of enantioenriched tertiary and quaternary stereogenic centers that are substituted with two further functionalizable alkenes. The first combination of the study involves the addition of stereochemically well-defined trisubstituted alkenylaluminum reagents to disubstituted allylic phosphates; the transformation commences with a silyl-directed stereoselective hydroalumination and finishes with an enantioselective Cu-catalyzed EAS promoted by a sulfonate bearing NHC. Such reactions deliver molecules that feature silicon containing trisubstituted olefin adjacent to the tertiary stereogenic center; subsequent conversion of the versatile silicon group to a proton reveals the first set of examples that incorporate pure Z alkene in Cu-catalyzed EAS. The stereoselective and concise synthesis of naturally occurring small molecule nyasol demonstrates the utility of the above method. On a different front, Ni-catalyzed site-selective hydroalumination of terminal alkynes has opened new possibility of introducing 1,1-disubstituted olefins in Cu-catalyzed EAS in the formation of tertiary stereogenic center containing enantioenriched organic building blocks. Such catalytic hydrometallation procedure also allows efficient access to alkenylaluminums that are derived from the conventionally problematic aromatic alkynes. The importance of efficient and selective synthesis of terminal aryl-substituted alkenylaluminum species is showcased in NHC-Cu-catalyzed EAS reactions that construct all-carbon quaternary stereogenic centers; a three-step convergent synthesis of natural product bakuchiol in enantiomerically enriched form highlights the potential of the current protocol in chemical synthesis. Chapter 4 Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylboronic Acid Pinacol Ester Reagents and Applications in Natural Product Synthesis. Within this chapter, we disclose the efficient utilization of alkenylboron reagents in Cu-catalyzed EAS reactions, which lead to highly site and enantioselective formations of molecules that contain both tertiary and quaternary carbon stereogenic centers. Unlike their aluminum-based counterparts, the use of boron-based reagents allows effective delivery of sensitive organic function groups, such as a carbonyl, which would be incompatible in the hydrometallation process with dibal-H. Our efforts accumulate to the first report of incorporation of all carbon quaternary centers that are substituted with unsaturated ester and aldehyde units in the EAS products; such a method facilitates the concise diastereo- and enantioselective synthesis of Pummerer's ketone and it's trans isomer. Further development of the above protocol towards the construction of tertiary stereogenic centers requires the design of new chiral sulfonate-containing imidazolinium salts as the ligand precursors and has lead to the employment of a broader range of alkenylboron species, which feature readily functionalizable motifs. Subsequent demonstrations in enantioselective synthesis of a variety of small molecule natural products showcase the utility
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Chang, Yejin. "Enantioselective Transformations of α- and β-Amino C-H Bonds Promoted by Cooperative Actions of Achiral and Chiral Lewis Acid Catalysts:." Thesis, Boston College, 2021. http://hdl.handle.net/2345/bc-ir:109179.
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Thesis advisor: Masayuki WasaThesis advisor: Amir H. Hoveyda
This dissertation describes the development of cooperative catalyst systems for the regio- and enantio-selective α- and β-amino C-H functionalization of N-alkylamines, inspired by the concepts of frustrated Lewis pairs (FLPs). Prior to this dissertation research, the development of effective and broadly applicable catalytic protocol to transform amino C-H bonds with high enantioselectivity remained as a formidable problem. In Chapter 1, the recent advances in the field of amino C-H functionalization through hydride transfer process that served as intellectual foundations for this dissertation research is presented. As highlighted in the first chapter, key challenges of amino C-H functionalization are: (1) unreactive nature of α, β- and/or γ-amino C-H bonds, (2) requirement for the use of precious metal-based catalysts and external oxidants under acidic/basic and harsh conditions, (3) use of directing groups for regioselectivity, and (4) poor functional group tolerance. Inspired by the unique capability of FLPs to activate otherwise unreactive molecules while disfavoring undesirable acid-base complexation, we have developed a protocol for enantioselective α-amino C-H functionalization of N-alkylamines, where chiral and achiral Lewis acid catalysts work cooperatively (Chapter 2). The application of the cooperative catalyst system comprising of B(C6F5)3, a chiral Lewis acid, and a Brønsted base to the enantioselective β-amino C-H functionalization is described in Chapter 3
Thesis (PhD) — Boston College, 2021
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Ramos, Hernández Isabel. "Can television promote a more progressive definition of rape and help delegitimize it?: Rape in Law and Order: Special Victims Unit." Thesis, Boston College, 2016. http://hdl.handle.net/2345/bc-ir:106783.
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Thesis advisor: Lynda Lytle HolmstromRape is a socially constructed behavior used in patriarchal societies to devalue women and ensure male supremacy. Being socially constructed means that the definition of rape can change. This thesis addresses the question of whether an established institution—television—can promote a more progressive definition of rape and help delegitimize it. It uses a feminist content analysis to examine the main themes on 14 episodes of Law and Order: Special Victims Unit (SVU) aired from 2012-2015. It is qualitative and inductive in nature, approached from a grounded theory perspective. The data demonstrate that SVU does, to some extent, present a more progressive view of rape instead of perpetuating the common stereotypes of rape. Essentially, SVU represents a new variety of definitions of rape that are reflective of white, privileged, heterosexual and young women's experiences in the United States. Race, class, sexual orientation and identity are barely taken into account even though many social inequalities based on them characterize American life
Thesis (BA) — Boston College, 2016
Submitted to: Boston College. College of Arts and Sciences
Discipline: Departmental Honors
Discipline: Sociology
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Renda, Adam. "Socially and Emotionally Competent Leadership: How School-based Leadership Practices That Promote Social and Emotional Learning Opportunities Shape the Work of Mental Health Staff." Thesis, Boston College, 2020. http://hdl.handle.net/2345/bc-ir:108801.
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Thesis advisor: Raquel Muniz CastroResearchers and educators recognize the benefits of developing students’ social and emotional competencies, but there is little research about the impact of leadership practices on the social and emotional competencies of adults in schools. The purpose of this qualitative case study was to investigate the relationship between leadership practices (i.e., what leaders think and do) that promote SEL opportunities, and how they shape the work of mental health staff (MHS) — defined in this study as, school counselors, and nurses. Findings indicated that school-based leaders promoted SEL opportunities for MHS when they (1) provided time to meet, (2) provided resources for professional development, (3) provided feedback through dialogue, (4) accessed MHS’ expertise through dialogue, and (5) provided coaching. These leadership practices shaped the work of MHS proactively. These findings suggest that principals should use social awareness to diagnose issues within the school, engage in responsible decision-making to set direction, and promote relationship-building to convince MHS to implement a plan
Thesis (EdD) — Boston College, 2020
Submitted to: Boston College. Lynch School of Education
Discipline: Educational Leadership and Higher Education
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Cheng-Tza, Pan, and 潘承澤. "Study on the Functional Analysis of Human bcl-x Gene Promoter." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/12246210629747015817.
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碩士國防醫學院
生物化學研究所
86
In order to study the regulation of bcl-x gene expression, the bcl-x gene promoter was isolated and subcloned into the luciferase reporter. A series of promoter deletions were made and the effect of these deletions and dexamethasone on promoter activities were analyzed by transient transfection. To increase the transfection efficiency, we modified the conventional method of calciumphosphate-DNA coprecipitation. This Hank's balanced salt solution (HBSS)-modified method showed marked improvement in transfection efficiency in cultured cell lines including TMK-1, HeLa, and MCF-7. By using this modified method, we carried out the bcl-x promoter analysis in TMK-1 and HEK-293 cells. Our results indicated that dexamethasone conferred only little (1.7 fold) of activation of bcl-x gene promoter and the promoter constructs exhibited very similar activity patterns in both of TMK-1 and HEK293 cells. A marked reduction in promoter activity was observed in constructs with deletions between -552 to - 402, suggest the presence of potential regulatory elements in this region. Detailed analysis of this region revealed that the region between -494 and -465 is important for full promoter activity. Competitive gel mobility shift assay using nuclear extracts from TMK-1 or HEK293 cells demonstrate the presence of a protein factor which binds with high affinity and specificity to this region. Similar experimental approaches were conducted for studying the extraordinary induction of c-myc gene expression in response to the transcription inhibitor, DRB in TMK- 1 cells. The regions correspond to P0 (-1457 to -763) and P1 (-763 to -254) promoters conferred 1.4 and 2.1 fold of DRB-induced activation, respectively, indicated that these c-myc promoter constructs may reflect the in vivo observations correctly. The regions which are responsible for major promoter activities were identified between -763 to -254 and -254 to +24, which correspond to the P1 and P2 promoters of c-myc gene. Taken together, these results revealed that P1 promoter may be responsible for the DRB-mediated c-myc transcription.
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Vander, Heiden Matthew G. "Bcl-x[subscript] L regulates mitochondrial homeostasis and promotes cell survival /." 2000. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:9978082.
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WANG, BEN-JIUAN, and 王本娟. "Analysis of Bar-code system in Drug Administration to Promote Medication Safety." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/63a7nn.
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碩士國立臺北護理健康大學
護理研究所
107
In recent years, various medical institutions have been implemented nursing information systems related to medical care. Especially in the emphasis on patient safety issues, while the Ministry of Health and Welfare has included the improve the safety of using medication as an annual goal. The Bar-code medication administration system (BCMA) is introduced into the drug administration to increase the accuracy of patient identification and drug identification and reduce the incidence of drug errors. this study evaluates the process and satisfaction of nurses using BCMA system to determine if the BCMA system meets the needs of users. Further, the patient safety report database was used to analyze the medication error events from 1993 to September 2018 to evaluate the effectiveness of the BCMA system. The study result showed that the average score of "perceived ease of use" was the highest (4.06±.574), and the "satisfaction of users" was the lowest (3.72±.712). Moreover, the study showed that "perceived ease of use", "perceived usefulness", "satisfaction of user" are positively correlated, and "perceived usefulness" to "satisfaction of users" scored are highest(β=0.313) correlation more than "perceived ease of use" (β=0.488). As for the comparison of medication errors before and after BCMA system, there are no significant differences in Variables, just like error characteristics(Z=-1.730、P>.084), attribute of the department(Z=-.059、P=.953), three shifts(Z=-.925、P=.355).The study concluded the research objects showed positive approval to the BCMA system, and summarized the experience to the project team to revise the system in the future.
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Huang, Chao-Hsien, and 黃朝先. "Molecular Dynamics Simulation for the Structural and Thermodynamic Properties of Human Bcl-2 Promoter Region." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/96972954382805904762.
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碩士國立陽明大學
生命科學暨基因體科學研究所
98
Bcl-2 (B-cell CLL/lymphoma 2) gene plays an important role in a number of human diseases, including lymphomas, breast carcinomas, cardiovascular and neurological disorders, whereas the expression of Bcl-2 gene is abnormally high or low. Research has discovered that there are two promoters, P1 and P2, in human Bcl-2 gene, and the major promoter P1 consists of tandem repeat GC bases, which is one of the keys in regulating Bcl-2 gene transcription. Thus, it is critical target in cancer, neuroprotective and tissue-protective therapies. In vitro, the experimental evidence shows that Bcl-2 promoter region can form a variety of G-quadruplex structures, which have a common planar structure with Hoogsteen H-bonds formed by four guanine bases. Therefore, a structure-based drug development that can be used to stabilize the G-quartet structure may lead to good drug candidates and potential therapies in human diseases. In the present study, molecular dynamics simulation and docking methods are used to investigate the mechanism on how Bcl-2 promoter interacts with drugs and can provide a more detailed insight into the structural stability of G-quadruplex complex in the rational drug design. We have performed the calculations of binding affinities on five carbazole derivatives with five distinct G-quadruplex structures of the human Bcl-2 promoter. In accord with the results, even though these results can be used to search for the best drug-binding sites and identify a potent drug, we also can verify a preferable G-quadruplex model structure for the wild type Bcl-2 promoter, because until now, only the structure of the mutated Bcl-2 promoter was determined. From the calculation of free energy by MMPBSA method, we also can find G-quadruplex is more stable in a high ionic strength condition. Our results are consistent with the in vitro experimental evidence. In the energy component analysis, we have found that the non-bonded interaction between drug and G-quadruplex reinforces the stability of the complex structure. We suggest that the structural properties of carbazole derivatives are important for the binding affinity and also provide a new direction for the design of carbazole derivatives. The result implies that a synthesized potent drug, 3,6-bis (1-methyl-3-vinylpyrazinium iodine) carbazole diiodide (BMVC-4) is a good human quadruplex stabilizer and also a good inhibitor of Bcl-2 promoter.
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"Molecular mechanism(s) of Tat transactivation of the HIV-1 long terminal repeat and the human Bcl-2 promoter." Tulane University, 1997.
Find full textAbstract:
The ability of HIV-1 Tat to stimulate transcription initiation from the HIV LTR suggests that the basal transcriptional machinery may be targeted by Tat. Results from the study presented herein demonstrate that HIV-1 Tat binds human TBP in vitro. Site-directed mutations within the activation domain of Tat (C22G and P18IS) that abrogate Tat transactivation in vivo fail to inhibit Tat-TBP binding. Full-length Tat, the activation domain of Tat alone, and a transactivation-defective mutant of Tat that lacks amino terminal amino acid residues 2-36 bind with equal efficiencies to TBP provided that the the H1, a helical domain that maps to amino acids 167-220 within the carboxyl terminus of TBP, is maintained. The data suggest that the core domain within activation domain of Tat and H1 $\alpha$ helical domain of TBP are involved in Tat-TBP interaction. Both wild-type and transactivation-defective mutant Tat bind to human TBP, thereby indicating that binding of the Tat activation domain to TBP may be necessary, yet insufficient, to mediate HIV-1 transactivation by Tat. The investigation of the functional significance of the direct interaction between Tat and TBP relative to Tat transactivation should contribute to the elucidation of the role of Tat in the assembly of functional transcription preinitiation complexes HIV-1 Tat also activates gene expression from cellular promoters. In the study presented herein, Tat reproducibly activates Bcl-2 promoter-directed gene expression (17-fold) in Hela cells. Analysis of deletion and site-directed Tat mutants for their respective abilities to activate Bcl-2 promoter-directed gene expression demonstrate that the N- and C-terminus of Tat are required to achieve maximal transactivation. Mutations within the N-terminal activation domain of Tat that inhibit Bcl-2 activation also inhibit Tat transactivation of the HIV-1 LTR, suggesting that the activation domain of Tat is required for transactivation of both the HIV LTR and the human Bcl-2 promoter. Analyses of wild-type and mutant Bcl-2 promoters demonstrate that the Tat responsive element is located both upstream of the Bcl-2 P1 promoter and P2 promoter regions. Elucidating the mechanism by which Tat transcriptionally activates Bcl-2 expression in cells may provide insight into the role of Tat as a regulator of cell survival and growth during AIDS pathogenesisacase@tulane.edu
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Tsou, Yu-Chi, and 鄒語綺. "Pro-inflammatory response-induced cell death involves in Bcl-2/adenovirus E1B 19-kDa- interacting protein 3 (BNIP3) and Bcl-2-associated death promoter (BAD) in the microglial cell and bladder cancer cell." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/8jrv9s.
Full textAbstract:
博士國立臺灣海洋大學
生命科學暨生物科技學系
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Acute inflammatory resulting from infection of microbial pathogen, chemical irritation or wounding may recruit inflammatory cells to elicit pro-inflammatory response to against infect. Moreover, chronic inflammation have reported to produce reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines to provide cancer-prone microenvironment, promoting cancer cell proliferation and survival, angiogenesis, migration and invasion leading to cancer progression. The pro-inflammatory response also involve in etiology of arteriosclerosis, bowel disease, asthma, autoimmune disease and neurodegenerative disease. The microglia-inflammatory response is play important role in neurodegenerative disease, including Alzheimer’s disease, Parkinson’s disease and multiple sclerosis disease. Chemical inhibitors of cyclin-dependent kinase (CDK) may prevent progression through the cell cycle and decrease inflammation-induced cell death. The mechanism of the protective effect of CDK inhibitors remains unexplored in microglia. Olomoucine was used to treat BV2 microglial cells, and the differential gene expression was examined by microarray. Western blotting analyzed the levels of inducible nitric oxide synthase (iNOS), cytochrome c and BNIP3. The promoter activity of iNOS and the transcriptional activity of E2F and NF-kappa B were measured by luciferase assay. Cell cycle and mitochondrial activity were examined by flow cytometry. Knock-down of BNIP3 was performed by lentivirus shRNA. We demonstrated that olomoucine inhibits cell proliferation, decreases NO production, reduces iNOS promoter activity, and alleviates NF-B and E2F transcriptional activation in lipopolysaccharide (LPS)-stimulated BV2 cells. The cell death elicited by LPS results from NO, and olomoucine can reduces LPS- and NO-induced cell death. Furthermore, olomoucine decreases the expression of BNIP3, a pro-apoptotic Bcl-2, and that knock-down of the gene promotes cell survival after NO treatment. CDK inhibitor reduces LPS-induced pro-inflammatory responses leading to the decrease of NO, which elicits cell death. Moreover, the protective effect of the inhibitor is due to the down-regulation of BNIP3, which involves mitochondrial disruption. Bladder cancer, a malignant urinary system tumor, is in the eighth position of the international cancer charts. Nowadays, Bacillus-Calmette-Guerin (BCG) immune therapy is the most common way for the treatment of bladder cancer. However, there are around 20 % patients unable to get any benefit from this, and the main mechanism of the effect of BCG is still unclear. Since BCG treatment have reported that macrophages might be recruited into the bladder to induce cancer cell death by the pro-inflammatory response, we further study the mechanism of the response involving cell death. We used LPS to treat macrophage Raw264.7 for the generation of conditioned medium (CM-LPS). Our results demonstrated that CM-LPS might cause cell death via a caspase-dependent manner in MBT-2 bladder cancer cells. As compared with CM-LPS, TNF-alpha involves the cell death. Using the 50 ng/ml of TNF-alpha was induced about 10 the cell death in MBT-2 cell, which decreasing by caspase-8 and pan caspase inhibitors. Moreover, TNF-alpha-induced AKT activation was found in MBT-2 cell by western blot, implying that the activating AKT may have anti-apoptotic activity. Since ceramide is generated after inflammation, we propose that ceramide may increase TNF-alpha-induced cell death in bladder cancer. C2-ceramide was induced the cell death via increasing the ROS production and loss of the mitochondrial membrane potential. Knockdown of the Bad was decreased the cell death, ROS and loss of the mitochondrial membrane potential. TNF-alpha combining with ceramide was exhibited chromatin condensation and DNA fragmentation by Hochest3334.2 staining assay. Moreover, using western blot to analyze AKT expression in MBT-2 bladder cell were exhibited that the AKT activation was decreased at the same time. We suggest that ceramide were promoted TNF-alpha-induced cell death via decreasing AKT activity and increasing Bad de-phosphorylation that involves cell death via mitochondrial disruption. These results are demonstrated that ceramide-mediated AKT inactivation may improve TNF-alpha-induced cell death in MBT-2 bladder cancer cells. Instead of Bad, ABT-737 can interact with the anti-apoptotic family of Bcl-2, Bcl-x/l and Bcl-w protein by BH3 domain. To study the role of the non-peptide BH3 mimetic ABT-737 in TNF--induced cell death. TNF- combining with ABT-737 was exhibited the cell death, the activity of caspase-8 and caspase-9 were increased in MBT-2 bladder cancer cell. Moreover, TNF-alpha and ABT-737 co-treatment were induced the Bim protein expression. And co-treatment were decreased the mitochondrial membrane potential, cytochrome c release and translocate the Bim to mitochondria. Our findings suggest that ABT-737 can promote the TNF-alpha-induced cell death by controlling the mitochondrial-mediation intrinsic cell death pathway. The future can improve the bladder cancer therapy, using the pre-clinical tests phase ABT-737 derivative combine with TNF-alpha to promote the BCG resistant bladder cancer cell death. In our results, we demonstrate that CDK inhibitor repressed the inflammatory by reducing NF-kappa B activity and NO production in BV2 microglia cell to decrease LPS-induce microglia cell death. In addition, TNF-/ceramide or ABT-737 was able to induce MBT-2 bladder cancer cell death. In this study, our findings display the multiple role of inflammatory response in different cell types in the protection or promotion of cell death.