In this thesis, two multidimensional spectroscopic methods — two-dimensional infrared (2D IR) spectroscopy and heterodyne 2D sum frequency generation (HD 2D SFG) spectroscopy — are applied to investigate ultrafast chemical exchange of organometallics in bulk solution and structural orientation of surface catalysts at interface, respectively.

2D IR spectroscopy is used to study the ultrafast chemical exchange of two organometallics compound ( Ru(S2C2(CF3)2)(CO)(PPh3)2 and Co(CNArMes2)4 ) occurring on the picosecond time scale. Combined with DFT simulation results, 2D IR provides direct evidence of the existence of various isomers. For the five-coordinate Ru complex, one isomers that serves as the intermediate of the axial-equatorial exchange was observed for the first time. Furthermore, our 2D IR works find the kinetic barriers of dynamic exchange between multiple isomers surprisingly low, consider both of the transition metal complexes under study have relatively large ligands. The low kinetic barriers are attributed to the small core-angle movement involved in the chemical exchange.2D IR is also applied to W(CO)6/dual cavity system to observe ultrafast intercavity nonlinear polariton interactions. Combined with a newly developed theory model, we show that the nonlinear interaction is realized by shared molecular anharmonicities among cavity modes, e.g. through mode delocalization, some molecules (with anharmonicity) are coupled by cavity modes adjacent to each other.

HD 2D SFG spectroscopy is used to study a model CO2 reduction catalyst, Re(diCNbpy)(CO)3Cl, as a monolayer on a gold surface. We show that short-range interactions with the surface can cause substantial line-shape differences between vibrational bands from the same molecules. This interaction can be explained as the result of couplings between CO vibrational modes of the catalyst molecules and the image dipoles on gold surface, which are sensitive to the relative distance between the molecule and the surface. Thus, by analysis of HD 2D SFG lineshape differences and polarization dependences of IR spectra, the ensemble-averaged orientation of the molecules on the surface can be determined unambiguously. The high sensitivity of HD 2D SFG spectra to short-range interactions can be applied to many other adsorbate–substrate interactions and therefore serve as a unique tool to determine adsorbate orientations on surfaces.

Meanwhile, surface molecules of the monolayers can adopt conformations with many different orientations. Thus, it is necessary to describe the orientations of surface molecular monolayers using both mean tilt angle and orientational distribution, which together we refer to as orientation heterogeneity. Orientation heterogeneity is difficult to measure. In most cases, in order to calculate the mean tilt angle, it is assumed that the orientational distribution is narrow. This assumption causes ambiguities in determining the mean tilt angle and loss of

orientational distribution information, which is known as the “magic angle” challenge. Using HD 2D SFG spectroscopy, we report a novel method to solve the “magic angle” challenge, by simultaneously measuring mean tilt angle and orientational distribution of molecular monolayers. Although applied to a specific system, this method is a general way to determine the orientation heterogeneity of an ensemble-averaged molecular interface.

Multicellular organisms require complex adaptive immune systems to maintain host defense from pathogens, but such systems must be precisely controlled to distinguish self from non-self and prevent autoimmunity. The autoimmune regulator (Aire) gene, a key transcriptional regulator expressed in medullary thymic epithelial cells (mTECs), has been shown to be crucial for central tolerance by inducing tissue specific antigen (TSA) expression in mTECs. Interestingly, we and others have also found extrathymic Aire-expressing cells (eTACs) in the secondary lymphoid organs such as the spleen and lymph nodes. eTACs are hematopoietic antigen- presenting cells (APCs) and consist of two similar cell types: CCR7+ Aire-expressing migratory dendritic cells (AmDCs) and an Aire-high population co-expressing Aire and retinoic acid receptor–related orphan receptor γt (RORγt) that we termed Janus cells (JCs). Functionally, eTACs are capable of enforcing deletion and anergy on self-reactive T cells, and self-antigen expression in eTACs is sufficient to prevent autoimmunity. Single cell RNA and ATAC sequencing revealed the transcriptional and genomic symmetry between eTACs and mTECs. This potentially identifies a core program driven by Aire that may influence self-representation and tolerance across the spectrum of immune development. Outside of self-antigen tolerance, we also revealed the crucial role of RORγt+ eTACs in maintaining oral tolerance by inducing food antigen-specific regulatory T cells and suppressing follicular helper cells. In the absence of JCs, mice develop more severe delayed-typed hypersensitivity response against dietary allergens. Taken together, these findings reveal the identity of various eTAC populations and provides novel insights into the mechanisms of immune tolerance against self and innocuous dietary antigens. Understanding the biology of this population may have significance for a range of clinical applications from autoimmunity to tumor immunity to maternal-fetal tolerance.

Given the fact that fuel efficiency and safety technologies are now being developed and deployed rapidly, saving gasoline and lives while incidentally rendering older analyses obsolete, this dissertation provides further discussions and insights on the relationship between fuel economy and vehicle safety using new empirical evidence. The different roles of size and weight are at the center of our concern; they have not yet been definitively separated in most studies. Another major component of this dissertation research is to study the impacts of the 2011 U.S. CAFE reform. This dissertation research employs an empirically estimated medium-run model to study the equilibrium effects of the 2011 CAFE reform. Micro-level data and counterfactual policy simulations are used to investigate the welfare implications of the “attribute-basing” structure (i.e., in which regulatory compliance depends upon some secondary attribute that is not the intended target of the regulation) of the footprint-based CAFE standards, including both potential benefits and likely costs.