1,281 research outputs found

    Catalytic Borylative Multicomponent Coupling Reactions and Novel Chemistry of Polycyclic Aromatic Hydrocarbons

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    Thesis advisor: Lawrence T. ScottThesis advisor: James P. MorkenExpeditious establishment of molecular complexity in a stereoselective manner is a prominent goal in organic synthesis. In this regard, multicomponent coupling reactions have received substantial attention due to their ability to access complex molecules from simple starting materials in a single step. Chapter 1 is a comprehensive review on catalytic bismetallative multicomponent reactions. The scope of this process in terms of both bismetallic reagents and the pi components are broad enough to be generally applied to more elaborate synthetic sequences. Particularly, contemporary applications of the bismetallative multicomponent coupling reactions, in which high enantio- and/or diastereoselectivities are displayed, have enabled the study of this area to make a significant step forward. Chapter 2 presents nickel-catalyzed coupling reactions of aldehyde, diene, and a diboron reagent in the presence of a trialkyl phosphine ligand. Compared to borylation reactions with one pi-component, these borylative multicomponent reactions (involving two pi components) lead to formation of a new C-C bond between the pi components as well as generation of highly functionalized, stereodefined products. Chapter 3 describes a remarkable turnover in regioselectivity of the borylative multicomponent coupling when PCy3 is replaced with P(SiMe3)3. In particular, the products from the reactions with P(SiMe3)3 feature three contiguous stereocenters and an alpha-chiral allylboronate. The effect of P(SiMe3)3 ligand on the product selectivity is intriguing. According to the experimental and computational results, it has an ability to act as an electron acceptor, which will facilitate reductive elimination from the intermediate nickel complex during the course of the reaction. In Chapter 4, we show that borylative ketone-diene coupling reactions can be accomplished in high yields and with excellent levels of diastereocontrol. This reaction occurs in a predictable fashion, yet with regioselection that is distinct from related aldehyde-diene coupling reactions. The reaction products from these coupling processes, which possess tertiary alcohol functionality and an allylic alcohol moiety, are particularly well suited for the preparation of polyketide natural products. Chapter 5 presents investigations on bowl-shaped geodesic polyarenes, which are the missing links between the "classic" planar polycyclic aromatic hydrocarbons (PAHs) and the spheroidal fullerenes. The present study has shown that open geodesic polyarenes can feature chemistry inherent to both classes of aromatics. The curved pi system induces unequal environments on the two faces of circumtrindene, significant strain energy to the molecule, and non-identical bond lengths. Along with the electronic effects, the stereoelectronic effect enabled the site-selective functionalization with fullerene-type chemistry. On the other hand, the edge carbons, which are not present in fullerenes, still possess reactivity of common planar PAHs. Chapter 6 describes the intermolecular oxidative cyclotrimerization reactions of alkenes and aromatic compounds with DDQ and trifluoromethanesulfonic acid. The Scholl-type oxidation reactions involving alkenes have never been demonstrated. Moreover, the DDQ/acid system has never been used for the intermolecular oxidative cyclization reactions. This convenient non-metallic reagent system (DDQ/TfOH) is advantageous over the metal-based Scholl-type oxidants because it eliminates the possibility of halogenation of aromatic compounds and the reduced oxidant can be reoxidized. In Chapter 7, the regioselective formation of cyclic trimers from substituted benzenes and heteroaromatic compounds is demonstrated. This DDQ/TfOH method provides a simple and convenient synthetic route toward star-shaped oligomers containing triphenylene or isotruxene cores. Furthermore, the experimental outcome suggests that this oxidative process proceeds by an electron transfer mechanism. This is the first experimental evidence for mechanistic details on the Scholl-type oxidation.Thesis (PhD) — Boston College, 2013.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry

    An overview of the national immunization policy making process: the role of the Korea expert committee on immunization practices

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    The need for evidence-based decision making in immunization programs has increased due to the presence of multiple health priorities, limited human resources, expensive vaccines, and limited funds. Countries should establish a group of national experts to advise their Ministries of Health. So far, many nations have formed their own National Immunization Technical Advisory Groups (NITAGs). In the Republic of Korea, the Korea Expert Committee on Immunization Practices (KECIP), established by law in the early 1990s, has made many important technical recommendations to contribute to the decline in vaccine preventable diseases and currently functions as a NITAG. It includes 13 core members and 2 non-core members, including a chairperson. Core members usually come from affiliated organizations in internal medicine, pediatrics, obstetrics, microbiology, preventive medicine, nursing and a representative from a consumer group, all of whom serve two year terms. Non-core members comprise two government officials belonging to the Korea Centers for Disease Control and Prevention (KCDC) and the Korea Food and Drug Administration. Meetings are held as needed, but at least twice a year, and sub-committees are formed as a resource for gathering, analyzing, and preparing information for the KECIP meetings. Once the sub-committees or the KCDC review the available data, the KECIP members discuss each issue in depth and develop recommendations, usually by a consensus in the meeting. The KECIP publishes national guidelines and immunization schedules that are updated regularly. KECIP's role is essentially consultative and the implementation of their recommendations may depend on the budget or current laws

    Comparison of Questions Used by Teachers with Expertise and Little Expertise in Elementary English Classes

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    Teachers pedagogical questions in a language classroom play a central role in students language and cognitive development. The purpose of this study was to compare the questions used by teachers with expertise and little expertise in the 5th grade-level elementary English classes and find what types of questions were used in common, and whether and how they were used differently among the teachers. This study also attempted to discover whether different question types were used depending on students levels of English. Video-recorded English lessons of 3 excellent teachers and 3 general teachers were transcribed and analyzed according to the functional aspects and cognitive aspects of questions, adapted from Long & Sato (1983) and Cunningham (1987). The analysis of the data led to the finding that expert teachers used more referential questions, comprehension check questions, and confirmation check questions in the main pedagogical activities of the lesson than the teachers with little expertise. In terms of cognitive questions, memory questions and convergent questions were predominantly used by all the teachers. Lastly, the teachers questions didnt reflect students different levels of English ability. The findings of the study have suggestions for teacher education, teaching, and research

    The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

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    In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment

    Immunization decision-making in the Republic of Korea: The structure and functioning of the Korea Advisory Committee on Immunization Practices

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    AbstractThe Korea Advisory Committee on Immunization Practices (KACIP), established by law in the early 1990s, makes recommendations on a range of issues related to the National Immunization Program. The Committee consists of 15 members and always includes the two government officials who belong to the Korea Centers for Disease Control and Prevention and the Korea Food and Drug Administration. Other members usually come from affiliated organizations and serve for 2-year terms. The KACIP depends on special-topics sub-committees or temporary advisory committees to gather and analyze data and to make recommendations which are normally reached by consensus and implemented by public sector health providers and private providers

    Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo.

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    BackgroundMany patients with nasopharyngeal carcinoma (NPC) face poor prognosis. Due to its hidden anatomical location, the tumor is usually diagnosed quite late, and despite initially successful treatment with radiation and cisplatin, many patients will relapse and succumb to the disease. New treatment options are urgently needed. We have performed preclinical studies to evaluate the potential NPC therapeutic activity of a newly developed analog of temozolomide (TMZ), an alkylating agent that is the current chemotherapeutic standard of care for patients with malignant glioma.ResultsTMZ was covalently conjugated to the natural monoterpene perillyl alcohol (POH), creating the novel fusion compound NEO212. Its impact on two NPC cell lines was studied through colony formation assays, cell death ELISA, immunoblots, and in vivo testing in tumor-bearing mice. In vitro, NEO212 effectively triggered tumor cell death, and its potency was significantly greater than that of its individual components, TMZ or POH alone. Intriguingly, merely mixing TMZ with POH also was unable to achieve the superior potency of the conjugated compound NEO212. Treatment of NPC cells with NEO212 inactivated the chemoprotective DNA repair protein MGMT (O6-methylguanine methyltransferase), resulting in significant chemosensitization of cells to a second round of drug treatment. When tested in vivo, NEO212 reduced tumor growth in treated animals.ConclusionOur results demonstrate anticancer activity of NEO212 in preclinical NPC models, suggesting that this novel compound should be evaluated further for the treatment of patients with NPC

    Comparison of tracheal temperature and core temperature measurement in living donor liver transplant recipients: a clinical comparative study

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    Abstract Background Body temperature is a vital sign, and temperature monitoring during liver transplantation is important. Tracheal temperature can be measured via an endotracheal tube with a temperature sensor on the cuff of the tube. This study aimed to investigate the accuracy and trending ability of tracheal temperature measurement compared to those of the core temperature measured at the esophagus and pulmonary artery (PA) in living donor liver transplant recipients. Methods Twenty-two patients who underwent living donor liver transplantation (LDLT) were enrolled. Patients were intubated using an endotracheal tube with a temperature sensor placed on the inner surface of the tube cuff. Tracheal, esophageal, and PA temperatures were recorded at five time points corresponding to the different phases of liver transplantation. The tracheal and esophageal, tracheal and PA, and esophageal and PA temperatures were compared using Bland–Altman analysis, four-quadrant plot/concordance analysis, and polar plot analysis. Results Bland–Altman analysis showed an overall mean bias (95% limits of agreement) between tracheal and esophageal temperatures of -0.10°C (-0.37°C to 0.18°C), with a percentage error of 0.27%; between tracheal and PA temperatures, -0.05°C (-0.91°C to 0.20°C), with a percentage error of -0.15%; and between esophageal and PA temperatures, 0.04°C (-0.27°C to 0.35°C), with a percentage error of 0.12%. The concordance rates between tracheal and esophageal temperatures, tracheal and PA temperatures, and esophageal and PA temperatures were 96.2%, 96.2%, and 94.94%, respectively. The polar plot analysis showed a mean angular bias (radial limits of agreement) of 4° (26°), -3° (13°), and 2° (21°). Conclusions Monitoring core temperature at the inner surface of the endotracheal tube cuff is accurate in all phases of LDLT with good trending ability; thus, it can be an excellent alternative for monitoring during LDLTs

    Selective disruption of an oncogenic mutant allele by CRISPR/Cas9 induces efficient tumor regression

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    Approximately 15% of non-small cell lung cancer cases are associated with a mutation in the epidermal growth factor receptor (EGFR) gene, which plays a critical role in tumor progression. With the goal of treating mutated EGFR-mediated lung cancer, we demonstrate the use of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) system to discriminate between the oncogenic mutant and wild-type EGFR alleles and eliminate the carcinogenic mutant EGFR allele with high accuracy. We targeted an EGFR oncogene harboring a single-nucleotide missense mutation (CTG > CGG) that generates a protospacer-adjacent motif sequence recognized by the CRISPR/Cas9 derived from Streptococcus pyogenes. Co-delivery of Cas9 and an EGFR mutation-specific single-guide RNA via adenovirus resulted in precise disruption at the oncogenic mutation site with high specificity. Furthermore, this CRISPR/Cas9-mediated mutant allele disruption led to significantly enhanced cancer cell killing and reduced tumor size in a xenograft mouse model of human lung cancer. Taken together, these results indicate that targeting an oncogenic mutation using CRISPR/Cas9 offers a powerful surgical strategy to disrupt oncogenic mutations to treat cancers; similar strategies could be used to treat other mutation-associated diseases.
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