C-H Functionalization of Substituted Aromatic Compounds Using Transition-Metal Catalysts

Department of Chemical EngineeringDevelopment of C–C formation methods has been a key research topic in synthetic organic chemistry fields. Recently, there have been extensive reports on C–H functionalization, a methodology to generate C–C bonds by activating C–H bond, while other C–N or C–O bond formations have been allowed. Traditional metal-catalyzed cross-coupling reaction has been one of the most useful synthetic methods for the formation of C–C bonds, a theme of the 2010 Nobel prize in chemistry. Yet, there is an inconvenience requiring laborious procedures to prepare organic halides or organometallic reagents. On the other hand, C–H activation can avoid these steps and it has influenced the broad field of chemical synthesis of small molecules, pharmaceuticals, fine chemicals, biomolecules, and organic-based materials. In this thesis, we have designed and performed both homogeneous and heterogeneous C–H functionalizations. Reaction optimization and substrate scope tests have been carried out to reveal the synthetic utilities. In the first chapter, we have established the first meta-selective C–H bond arylation of anilides using copper-exchanged zeolites. The Cu-zeolites have showed high catalytic activities on the low copper concentration (0.5 mol%). And we have demonstrated that Cu-zeolites are chemically stable and robust as recyclable catalysts. In the second chapter, we demonstrated a microwave-assisted meta-selective direct (hetero)arylation of pivanilides to accelerate copper catalysis. The ligand-free CuII-β system has showed improved catalytic stability over consecutive runs. In addition, homogeneous Cu(OTf)2 and heterogeneous CuII-β zeolite catalysts have been systematically compared to reveal their catalytic characteristics. In the last chapter, the main focus of the thesis, we have designed a straightforward synthetic route to access tailored triphenylenes as graphene segments. We have achieved mono- and bis-annulation of pivanilides in a one-step. Moreover, the method has been extended to the application of field-effect transistor sensor for alcohol vapor detection.ope

Development of a performance-based approach for collision avoidance and mitigation

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2003.Includes bibliographical references (leaves 70-72).This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Many threat assessment algorithms are based on a collection of threshold equations that predict when a collision is to occur. The fact that there are numerous algorithms suggests a need to understand the underlying principles behind the equation design and threshold settings. This thesis presents a methodology to develop appropriate alerting thresholds based on performance metrics. This also allows us to compare different alerting algorithms and evaluate alerting systems. The method is a performance-based approach in state-space. It can be used as a stand alone system for real-time implementation or a threshold design tool in conjunction with any chosen alerting algorithm or sensor system. Using carefully prescribed trajectory models (which may include uncertainties), the performance tradeoff with and without an alert can be predicted for different states along the course of an encounter situation. This information can then be used to set appropriate threshold values for the desired alerting logic. The development of the threshold criteria for a rear-end collision warning system is given as an example. Though the approach given is presented as a threshold design tool, the methodology is self-contained as a threat assessment logic. The possibility exists to compute the performance measures on-the-fly from which alerting decisions can be made directly. We demonstrate the methodology on Lincoln LS concept vehicle with a GPS-based system and a full-cab driving simulator as prototypes. Application examples, a collision mitigation by braking system and a face tracking warning system, are shown to handle the universality of the performance-based approach. For illustrative purposes, a vision-based system (post-processed off-line) is compared with the GPSbased system.by Ji Hyun Yang.S.M

Analysis and detection of driver fatigue caused by sleep deprivation

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2007.Includes bibliographical references (leaves 167-181).Human errors in attention and vigilance are among the most common causes of transportation accidents. Thus, effective countermeasures are crucial for enhancing road safety. By pursuing a practical and reliable design of an Active Safety system which aims to predict and avoid road accidents, we identify the characteristics of drowsy driving and devise a systematic way to infer the state of driver alertness based on driver-vehicle data. Although sleep and fatigue are major causes of impaired driving, neither effective regulations nor acceptable countermeasures are available yet. The first part of this thesis analyzes driver-vehicle systems with discrete sleep-deprivation levels, and reveals differences in the performance characteristics of drivers. Inspired by the human sleep-wake cycle mechanism and attributes of driver-vehicle systems, we design and perform human-in-the-loop experiments in a test bed built with STISIM Drive, an interactive fixed-based driving simulator. In the simulated driving, participants were given various driving tasks and secondary tasks for both non and partially sleep-deprived conditions. This experiment demonstrates that sleep deprivation has a greater effect on rule-based tasks than on skill-based tasks; when drivers are sleep-deprived, their performance of responding to unexpected disturbances degrades while they are robust enough to continue such routine driving tasks as straight lane tracking, following a lead vehicle, lane changes, etc. In the second part of the thesis we present both qualitative and quantitative guidelines for designing drowsy driver detection systems in a probabilistic framework based on the Bayesian network paradigm and experimental data.(cont.) We consider two major causes of sleep, i.e., sleep debt and circadian rhythm, in the framework with various driver-vehicle parameters, and also address temporal aspects of drowsiness and individual differences of subjects. The thesis concludes that detection of drowsy driving based on driver-vehicle data is a feasible but difficult problem which has diverse issues to be addressed; the ultimate challenge lies in the human operator.by Ji Hyun Yang.Ph.D

Phytohormone abscisic acid control RNA-dependent RNA polymerase 6 gene expression and post-transcriptional gene silencing in rice cells

RNA-dependent RNA polymerase 6 (RDR6) catalyses dsRNA synthesis for post-transcriptional gene silencing (PTGS)-associated amplification and the generation of endogeneous siRNAs involved in developmental determinations or stress responses. The functional importance of RDR6 in PTGS led us to examine its connection to the cellular regulatory network by analyzing the hormonal responses of RDR6 gene expression in a cultured cell system. Delivery of dsRNA, prepared in vitro, into cultured rice (Oryza sativa cv. Japonica Dongjin) cells successfully silenced the target isocitrate lyase (ICL) transcripts. Silencing was transient in the absence of abscisic acid (ABA), while it became persistent in the presence of ABA in growth medium. A transcription assay of the OsRDR6 promoter showed that it was positively regulated by ABA. OsRDR6-dependent siRNA(ICL) generation was also significantly up-regulated by ABA. The results showed that, among the five rice OsRDR isogenes, only OsRDR6 was responsible for the observed ABA-mediated amplification and silencing of ICL transcripts. We propose that ABA modulates PTGS through the transcriptional control of the OsRDR6 gene

‘Evidence of an auxin signal pathway, microRNA167-ARF8-GH3, and its response to exogenous auxin in cultured rice cells’

MicroRNA167 (miR167) was shown to cleave auxin responsive factor 8 (ARF8) mRNA in cultured rice cells. MiR167 level was found to be controlled by the presence of auxin in the growth medium. When cells grew in auxin-free medium, miR167 level decreased, resulting in an increase in the level of ARF8 mRNA. Cells growing in the normal growth medium containing auxin showed a reversed trend. It was also shown that expression of OsGH3-2, an rice IAA-conjugating enzyme, was positively regulated by ARF8. Delivery of synthesized miR167 into cells led to decrease of both ARF8 mRNA and OsGH3-2 mRNA. This study provides an evidence in which the exogeneous auxin signal is transduced to OsGH3-2 through miR167 and ARF8 in sequence. This proposed auxin signal transduction pathway, auxin-miR167-ARF8-OsGH3-2, could be, in conjunction with the other microRNA-mediated auxin signals, an important one for responding to exogeneous auxin and for determining the cellular free auxin level which guides appropriate auxin responses

Accurate and Efficient Estimation of Small P-values with the Cross-Entropy Method: Applications in Genomic Data Analysis

Small $p$-values are often required to be accurately estimated in large scale genomic studies for the adjustment of multiple hypothesis tests and the ranking of genomic features based on their statistical significance. For those complicated test statistics whose cumulative distribution functions are analytically intractable, existing methods usually do not work well with small $p$-values due to lack of accuracy or computational restrictions. We propose a general approach for accurately and efficiently calculating small $p$-values for a broad range of complicated test statistics based on the principle of the cross-entropy method and Markov chain Monte Carlo sampling techniques. We evaluate the performance of the proposed algorithm through simulations and demonstrate its application to three real examples in genomic studies. The results show that our approach can accurately evaluate small to extremely small $p$-values (e.g. $10^{-6}$ to $10^{-100}$). The proposed algorithm is helpful to the improvement of existing test procedures and the development of new test procedures in genomic studies.Comment: 34 pages, 1 figure, 4 table

Prevalence of sarcopenia and sarcopenic obesity in Korean adults: The Korean Sarcopenic Obesity Study (KSOS)

*Context:* Sarcopenic obesity (SO), a combination of excess weight and reduced muscle mass and/or strength, is suggested to be associated with an increased risk of adverse health outcomes. 
*Objectives:* To examine the prevalence and characteristics of Sarcopenic and SO defined by using different indices such as Appendicular Skeletal muscle Mass (ASM)/height^2^ and Skeletal Muscle Index (SMI (%): skeletal muscle mass (kg)/weight (kg) × 100) for Korean adults. 
*Methods:* 591 participants were recruited from the Korean Sarcopenic Obesity Study (KSOS) which is an ongoing prospective observational cohort study. Analysis was conducted in 526 participants (328 women, 198 men) who had complete data on body composition using Dual X-ray absorptiometry and computed tomography. 
*Results:* The prevalence of sarcopenia and SO increases with aging. Using two or more standard deviations (SD) of ASM/height^2^ below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in men and 4.1% and 1.7% in women over 60 years of age. However, using two or more SD of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1% respectively in men and 14.2% and 12.5% respectively in women. As defined by SMI, subjects with SO had 3 times the risk of metabolic syndrome (OR = 3.03, 95% confidence interval (CI) = 1.26-7.26) and subjects with non-sarcopenic obesity had approximately 2 times the risk of metabolic syndrome (OR = 1.89, 95% CI = 1.18-3.02) compared with normal subjects. 
*Conclusion:* Obese subjects with relative sarcopenia were associated with a greater likelihood for metabolic syndrome. As Koreans were more obese and aging, the prevalence of SO and its impact on health outcomes are estimated to be rapidly grow. Further research is requested to establish the definition, cause and consequences of SO.
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