Moral Dilemmas and Moral Theories

In my dissertation, I argue for the existence of moral dilemmas and draw out the implications of their existence on major moral theories. A moral dilemma arises when: a moral agent holds moral principles entailing inconsistent actions, the moral principles do not override each other, and the moral agent cannot perform all the actions entailed by moral principles at the same time. I defend the arguments for moral dilemmas by considering objections to them and offering replies to those objections. On the other hand, I raise objections to the arguments against moral dilemmas in order to refute them. Having argued for the existence of moral dilemmas, I draw out the implications of their existence on major moral theories—Kant’s ethical theory, Mill’s utilitarianism, and virtue ethics. The existence of moral dilemmas is inconsistent with Kant’s ethical theory. For Kant, It is inconceivable to suppose that two actions could both be necessary when doing one prevents doing the other. If a moral agent has a duty to perform a certain action, then the moral agent cannot also have a duty to perform another action incompatible with it. The existence of moral dilemmas, however, is consistent with both Mill’s utilitarianism and virtue ethics. Mill’s utilitarianism allows for a situation where the alternative courses of action produce the same amount of utilities. Even a fully virtuous person may face a situation where he or she cannot tell which course of action is the right one. Yet, the existence of moral dilemmas, favors virtue ethics over Mill’s utilitarianism; it provides a better account of moral residue—the feelings of remorse or guilt a moral agent experiences after violating one of the conflicting moral principles. A moral agent that shows no emotional response or feels merely regret about violating a moral principle exhibits a morally callous character. On the other hand, the moral agent with a virtuous character would not only take conflicting moral principles seriously but he or she would also experience strong negative emotions about violating one of them. The kind of emotional response that the moral agent shows reveals the type of character that he or she possesses

Computing Algorithm for an Equilibrium of the Generalized Stackelberg Game

The $1-N$ generalized Stackelberg game (single-leader multi-follower game) is intricately intertwined with the interaction between a leader and followers (hierarchical interaction) and the interaction among followers (simultaneous interaction). However, obtaining the optimal strategy of the leader is generally challenging due to the complex interactions among the leader and followers. Here, we propose a general methodology to find a generalized Stackelberg equilibrium of a $1-N$ generalized Stackelberg game. Specifically, we first provide the conditions where a generalized Stackelberg equilibrium always exists using the variational equilibrium concept. Next, to find an equilibrium in polynomial time, we transformed the $1-N$ generalized Stackelberg game into a $1-1$ Stackelberg game whose Stackelberg equilibrium is identical to that of the original. Finally, we propose an effective computation procedure based on the projected implicit gradient descent algorithm to find a Stackelberg equilibrium of the transformed $1-1$ Stackelberg game. We validate the proposed approaches using the two problems of deriving operating strategies for EV charging stations: (1) the first problem is optimizing the one-time charging price for EV users, in which a platform operator determines the price of electricity and EV users determine the optimal amount of charging for their satisfaction; and (2) the second problem is to determine the spatially varying charging price to optimally balance the demand and supply over every charging station.Comment: 37 pages, 10 figure

Nanomechanical characterization of quantum interference in a topological insulator nanowire

The discovery of two-dimensional gapless Dirac fermions in graphene and topological insulators (TI) has sparked extensive ongoing research toward applications of their unique electronic properties. The gapless surface states in three-dimensional insulators indicate a distinct topological phase of matter with a non-trivial Z2 invariant that can be verified by angle-resolved photoemission spectroscopy or magnetoresistance quantum oscillation. In TI nanowires, the gapless surface states exhibit Aharonov-Bohm (AB) oscillations in conductance, with this quantum interference effect accompanying a change in the number of transverse one-dimensional modes in transport. Thus, while the density of states (DOS) of such nanowires is expected to show such AB oscillation, this effect has yet to be observed. Here, we adopt nanomechanical measurements that reveal AB oscillations in the DOS of a topological insulator. The TI nanowire under study is an electromechanical resonator embedded in an electrical circuit, and quantum capacitance effects from DOS oscillation modulate the circuit capacitance thereby altering the spring constant to generate mechanical resonant frequency shifts. Detection of the quantum capacitance effects from surface-state DOS is facilitated by the small effective capacitances and high quality factors of nanomechanical resonators, and as such the present technique could be extended to study diverse quantum materials at nanoscale.Comment: 15+16 pages, 4+11 figure

Synergetic Influence of Microcrystalline Quartz and Alkali Content in Aggregate on Deterioration of Concrete Railroad Ties Used for 15 Years in High-Speed Railways

This study investigated the deteriorations of precast prestressed concrete (PSC) ties that were used for 15 years in high-speed railways in Korea and its damaging mechanism. The collected PSC ties with longitudinal cracks on sides and map cracks on surfaces exhibited strength degradation. The deteriorations were likely related to alkali-silica reaction (ASR) and delayed ettringite formation (DEF) together, given that the presence of massive ettringite crystals and the decomposition of ASR gel were found from microstructural analyses. Although there were no typical reactive siliceous aggregates for ASR in this study, ASR cracks were generated in the PSC ties. This is because the aggregates in the PSC ties with cracks were potentially reactive, and its high alkali-silica reactivity was likely attributable to the presence of microcrystalline quartz, supplying reactive SiO2 to trigger ASR. Furthermore, the alkali content in aggregates was associated with the deterioration of the PSC ties. The alkali-bearing minerals in aggregates (i.e., alkali feldspars) likely supplied enough alkalis for ASR. Besides, micas in aggregates could promote ASR due to their porous structure, which helps easy water ingress

Differential importance of nucleus accumbens Ox1Rs and AMPARs for female and male mouse binge alcohol drinking

Alcohol use disorder exhausts substantial social and economic costs, with recent dramatic increases in female problem drinking. Thus, it is critically important to understand signaling differences underlying alcohol consumption across the sexes. Orexin-1 receptors (Ox1Rs) can strongly promote motivated behavior, and we previously identified Ox1Rs within nucleus accumbens shell (shell) as crucial for driving binge intake in higher-drinking male mice. Here, shell Ox1R inhibition did not alter female mouse alcohol drinking, unlike in males. Also, lower dose systemic Ox1R inhibition reduced compulsion-like alcohol intake in both sexes, indicating that female Ox1Rs can drive some aspects of pathological consumption, and higher doses of systemic Ox1R inhibition (which might have more off-target effects) reduced binge drinking in both sexes. In contrast to shell Ox1Rs, inhibiting shell calcium-permeable AMPA receptors (CP-AMPARs) strongly reduced alcohol drinking in both sexes, which was specific to alcohol since this did not reduce saccharin intake in either sex. Our results together suggest that the shell critically regulates binge drinking in both sexes, with shell CP-AMPARs supporting intake in both sexes, while shell Ox1Rs drove drinking only in males. Our findings provide important new information about sex-specific and -general mechanisms that promote binge alcohol intake and possible targeted therapeutic interventions

Programmable RNA base editing with photoactivatable CRISPR-Cas13

Abstract CRISPR-Cas13 is widely used for programmable RNA interference, imaging, and editing. In this study, we develop a light-inducible Cas13 system called paCas13 by fusing Magnet with fragment pairs. The most effective split site, N351/C350, was identified and found to exhibit a low background and high inducibility. We observed significant light-induced perturbation of endogenous transcripts by paCas13. We further present a light-inducible base-editing system, herein called the padCas13 editor, by fusing ADAR2 to catalytically inactive paCas13 fragments. The padCas13 editor enabled reversible RNA editing under light and was effective in editing A-to-I and C-to-U RNA bases, targeting disease-relevant transcripts, and fine-tuning endogenous transcripts in mammalian cells in vitro. The padCas13 editor was also used to adjust post-translational modifications and demonstrated the ability to activate target transcripts in a mouse model in vivo. We therefore present a light-inducible RNA-modulating technique based on CRISPR-Cas13 that enables target RNAs to be diversely manipulated in vitro and in vivo, including through RNA degradation and base editing. The approach using the paCas13 system can be broadly applicable to manipulating RNA in various disease states and physiological processes, offering potential additional avenues for research and therapeutic development

Nucleus Accumbens Shell and mPFC but not Insula Orexin-1 Receptors Promote Excessive Alcohol Drinking

Addiction to alcohol remains a major social and economic problem, in part because of the high motivation for alcohol that humans exhibit and the hazardous binge intake this promotes. Orexin-1-type receptors (OX1Rs) promote reward intake under conditions of strong drives for reward, including excessive alcohol intake. While systemic modulation of OX1Rs can alter alcohol drinking, the brain regions that mediate this OX1R enhancement of excessive drinking remain unknown. Given the importance of the nucleus accumbens (NAc) and anterior insular cortex (aINS) in driving many addictive behaviors, including OX1Rs within these regions, we examined the importance of OX1Rs in these regions on excessive alcohol drinking in C57BL/6 mice during limited-access alcohol drinking in the dark cycle. Inhibition of OX1Rs with the widely used SB-334867 within the medial NAc Shell (mNAsh) significantly reduced drinking of alcohol, with no effect on saccharin intake, and no effect on alcohol consumption when infused above the mNAsh. In contrast, intra-mNAsh infusion of the orexin-2 receptor TCS-OX2-29 had no impact on alcohol drinking. In addition, OX1R inhibition within the aINS had no effect on excessive drinking, which was surprising given the importance of aINS-NAc circuits in promoting alcohol consumption and the role for aINS OX1Rs in driving nicotine intake. However, OX1R inhibition within the mPFC did reduce alcohol drinking, indicating cortical OXR involvement in promoting intake. Also, in support of the critical role for mNAsh OX1Rs, SB within the mNAsh also significantly reduced operant alcohol self-administration in rats. Finally, orexin ex vivo enhanced firing in mNAsh neurons from alcohol-drinking mice, with no effect on evoked EPSCs or input resistance; a similar orexin increase in firing without a change in input resistance was observed in alcohol-naïve mice. Taken together, our results strongly suggest that OX1Rs within the mNAsh, but not the aINS, play a central role in driving excessive alcohol drinking

Estimation of speech absence uncertainty based on multiple linear regression analysis for speech enhancement

a b s t r a c t We propose a novel approach to improve the performance of speech enhancement systems by using multiple linear regression to improve the technique of estimating the speech presence uncertainty. Conventional speech enhancement techniques use a fixed ratio Q of the a priori probability of speech presence and speech absence, or determine the value of Q simply by comparing one particular parameter against a threshold in deriving the speech absence probability (SAP) associated with the speech presence uncertainty. To further improve the performance of the SAP, we attempt to adaptively change Q according to a linear model consisting of the regression coefficients obtained by results from multiple linear regression analysis and two principal parameters: a priori SNR and the ratio between the local energy of the noisy speech and its derived minimum since these parameters correlate strongly with the value of Q. Distinct values of Q for each frequency in each frame are consequently assigned in time which leads to improved tracking performance of speech absence uncertainty and thus better performance of the proposed speech enhancement compared to conventional approaches. The superiority of the proposed approach is confirmed through extensive objective and subjective evaluations under various noise conditions