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A fundamental phenomenon in biology is the organization of cells into subcellular compartments and structures that contain distinct molecules and perform unique functions. Studying the mechanisms by which biological events occur with subcellular specificity is critical for understanding biological principles and designing precise treatments. This thesis presents investigations into the mechanisms underlying subcellular targeting specificities in two topics: delivery of nitrogen-containing-bisphosphonates (N-BPs) to its pharmacological target, and activity-dependent, glia-mediated synapse elimination during postnatal development. N-BPs are a class of drugs widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies have established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Through a CRISPRi-mediated genome-wide screen, we identified SLC37A3 (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We discovered that SLC37A3 forms a complex with ATRAID (all-trans-retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. During brain development, synapses are initially formed in excess. Redundant synapses are subsequently eliminated in an activity-dependent manner, with weaker synapses being preferentially removed. Recent studies have demonstrated that microglia and astrocytes utilize phagocytic receptors to recognize ‘eat-me’ signals deposited on redundant synapses for synaptic engulfment. However, it is not known how these ‘eat-me’ signals specifically target weaker synapses. Caspase 3, a protease crucial for apoptosis execution, is activated at synapses that are weakened through long-term depression (LTD). In addition, caspase 3 activation during apoptosis triggers the display of various “eat-me” signals recognized by phagocytes for cell debris clearance. We demonstrate that mice deficient in caspase 3 show significant defects in glia-mediated synapse elimination and neural circuit remodeling in the developing visual pathway. We propose that caspase 3 activation at weakened synapses is a key molecular event that links synaptic strength to external signals recognized by glia for synapse removal.

The urban anthropogenic heat flux (AHF), which is one integral part of the deteriorating urban thermal environment, is seldom discussed for its ambiguity to accurately measure over heterogeneous land surfaces. Here, relying on remote sensing technology and meteorological models, AHF is estimated and illustrated on April 18, 2017 over NYC area. Furthermore, a few independent variables are developed in order to possibly explain the variations of anthropogenic heat flux, including road density, impervious surface area percent, building shape coefficient, standard deviation of building height and street canyon aspect ratio. On both community district and census tract level, four of the five variables (road density, impervious surface area percent, standard deviation of building height and street canyon aspect ratio) demonstrate steady significant linear relationships with anthropogenic heat flux. A final spatial error model suggests that 71.8% of AHF variation can be explained after spatial error term was incorporated. The results implicate that some planning and designing indices associated with urban developments like buildings and roads should be taken into consideration for a benign thermal environment. In this case, a compact sub-city level spatial unit with diversified building heights and minimum exploitation to pervious land is a good example in terms of AHF mitigation.

Polymer electrolytes are indispensable in numerous electrochemical systems. Existing polymer electrolytes rarely meet all technical demands by their applications (e.g., high ionic conductivity and good mechanical strength), and new types of polymer electrolytes continue to be developed. In this dissertation, the molecular structure and dynamics of three emerging types of polymer electrolytes featuring Coulombic liquids, i.e., polymerized ionic liquids (polyILs), nanoscale ionic materials (NIMs), and polymeric ion gels, were investigated using molecular dynamics (MD) simulations to help guide their rational design. First, the molecular structure and dynamics of a prototypical polyILs, i.e., poly(1-butyl-3-vinylimidazolium hexafluorophosphate), supported on neutral and charged quartz substrates were investigated. It was found that the structure of the interfacial polyILs is affected by the surface charge on the substrate and deviates greatly from that in bulk. The mobile anions at the polyIL-substrate interfaces diffuse mainly by intra-chain hopping, similar to that in bulk polyILs. However, the diffusion rate of the interfacial mobile anions is much slower than that in bulk due to the slower decay of their association with neighboring polymerized cations. Second, the structure and dynamics of polymeric canopies in the modeling NIMs where the canopy thickness is much smaller than their host nanoparticle were studied. Without added electrolyte ions, the polymeric canopies are strongly adsorbed on the solid substrate but maintain modest in-plane mobility. When electrolyte ion pairs are added, the added counter-ions exchange with the polymeric canopies adsorbed on the charged substrate. However, the number of the adsorbed electrolyte counter-ions exceeds the number of desorbed polymeric canopies, which leads to an overscreening of the substrate's charge. The desorbed polymers can rapidly exchange with the polymers grafted electrostatically on the substrate. Finally, the molecular structure and dynamics of an ion gel consisting of PBDT polyanions and room-temperature ionic liquids (RTIL) were studied. First, a semi-coarse-grained model was developed to investigate the packing and dynamics of the ions in this ion gel. Ions in the interstitial space between polyanions exhibit distinct ordering, which suggests the formation of a long-range electrostatic network in the ion gel. The dynamics of ions slow down compared to that in bulk due to the association of the counter-ions with the polyanions' sulfonate groups. Next, the RTIL-mediated interactions between charged nanorods were studied. It was discovered that effective rod-rod interaction energy oscillates with rod-rod spacing due to the interference between the space charge near each rod as the two rods approach each other. To separate two rods initially positioned at the principal free energy minimum, a significant energy barrier (~several kBT per nanometer of the nanorod) must be overcome, which helps explain the large mechanical modulus of the PBDT ion gel reported experimentally.

The chemical structure of deoxyribonucleic acid, or DNA, is a unique double helix structure. This structure has nanoscale features that could improve device performance. Dopants were introduced into such a nanoscale structure to obtain enhanced optical luminescence performance. The thin film process of DNA was studied. High optical quality thin film was made of surfactant-reacted DNA material (DNA-CTMA). Thin film optical properties including transmission, optical waveguide loss, and index of refraction were studied and results showed that the DNA-CTMA material has a very low optical loss in both visible and infrared (IR) spectra. Surface morphology studies showed that the DNA-CTMA thin film is a good candidate for optical device fabrication.Sulforhodamine 640 (SRh) laser dye was doped in DNA-CTMA thin film. Such a doped thin film showed enhanced photoluminescence over PMMA material. Mechanism of enhanced performance was discussed and examined experimentally. Interference lithography was chosen for distributed feedback (DFB) laser device fabrication on SRh doped DNA-CTMA thin film. Both DNA-CTMA:SRh and PMMA:SRh DFB devices showed stimulated emission while DNA-CTMA material has lower threshold and higher efficiency than PMMA.

There has been an increasing need and great interest in both fundamental science and cutting-edge technology to modify the surfaces of nanoparticles. Such a surface modification must be within a nanoscale in terms of structure, composition, and uniformity. The great challenge therefore lies critically on the deposition of a film on the order of a few nanometers on the surfaces of the nanoparticles. In this thesis, the uniform deposition of ultrathin polymer films of 2 nm on the surfaces of alumina nanoparticles by plasma polymerization was demonstrated. The deposited film can also be tailored to multi-layers. One layer to three layers has been tried in the experiments. Scanning Electron Microscopy (SEM), High Resolution Electron Microscopy (HREM), Time-of-flight Secondary Ion Mass Spectroscopy (TOF-SIMS), X-ray Diffraction (XRD) and Micro hardness were used to confirm the pyrrole coating on the nanoparticle surfaces, the surface morphology and the mechanical properties. Using such a nanocoating, it opens a window to alter the intrinsic properties of materials that cannot be achieved by conventional methods and materials.