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Frontotemporal lobar degeneration (FTLD) is a devastating, clinically heterogeneous neurodegenerative disease that results in the progressive atrophy of the frontal and temporal lobes of the brain. Most often presenting with drastic alterations in personality and behavior, as well as a gradual decline in language capabilities, FTLD is the second leading cause of early-onset dementia only after Alzheimer’s disease. One of the major causes of familial FTLD is haploinsufficiency of the protein, progranulin (PGRN), resulting from mutation in the granulin (GRN) gene. Interestingly, PGRN shows a dosage-dependent disease correlation, and GRN mutation resulting in complete loss of PGRN causes the lysosomal storage disease (LSD), neuronal ceroid lipofuscinosis (NCL). In this text, my co-workers and I demonstrate that PGRN is proteolytically processed in the lysosome into discrete granulin peptides, which may possess distinct functions. We have independently found interactions between PGRN or granulin peptides and three lysosomal hydrolases: Cathepsin D (CTSD), glucocerebrosidase (GBA), and ɑ-N-acetylgalactosaminidase (NAGA). The activity of each of these enzymes was found to be reduced in Grn-/- mice, indicating that a potential mechanism of PGRN-related disease may be dysfunction of multiple lysosomal hydrolases. In addition to possessing an indeterminate lysosomal function, PGRN has also been shown to be a neurotrophic factor. Completion of a high-throughput screen searching for the receptor that mediates this function identified cluster of differentiation 68 (CD68) and neuropilin 2 (NRP2) as putative PGRN receptors. A second protein that has become of interest to the study of FTLD is TMEM106B. Variants of TMEM106B have been associated with an increased risk of developing FTLD, especially in cases of GRN mutation (FTLD-GRN). Although TMEM106B is known to be an endolysosomal transmembrane protein that regulates lysosomal morphology and degradative capacity, its exact function is unclear. Our current findings suggest that TMEM106B may regulate cellular levels of the phosphoinositide, PI(3,5)P2. In summary, our work supports a lysosomal role of the FTLD- and NCL-related protein, PGRN, and identifies a novel function of the FTLD risk factor, TMEM106B.

This thesis is a study of quantum turbulence in superfluid helium. Superfluid he- lium consists of two interpenetrating fluids, a viscous normal fluid and an inviscid superfluid, coupled by a mutual friction. The thesis is divided in two parts. The first part deals with fully developed turbulence. In analogy to classical turbulence theory, I develop a two-fluid shell model to study superfluid turbulence. I investigate the energy spectra and the balance of fluxes between the two fluids as a function of temperature in continuously forced turbulence and show how both fluids gener- ate the classical k−5/3 Kolmogorov scaling law within the inertial subrange, whilst simultaneously exhibiting deviations from this law outside the subrange due to the mutual friction force. I furthermore investigate the decay of turbulence in the ab- sence of forcing. I compare my results with experiments and existing calculations. I find that, at sufficiently low temperatures a build-up of energy develops at high wavenumbers suggesting the need for a further dissipative effect, such as the Kelvin wave cascade and phonon emission. The second part of this thesis is concerned with complex vortex flows. It is well known that two coaxial vortex rings can leapfrog about each other. By direct numerical simulation, I show that in superfluid helium the effect can be generalised to a large number of vortex rings, which form a toroidal bundle. The bundle is shown to be robust, travelling a significant distance compared to its diameter, whilst at the same time becoming linked and turbulent. I also discuss the effects of friction at non-zero temperatures, and show how in this case the presence of normal fluid rotation is necessary for the stability of the bundle. Although I am unable to model numerically the number of rings realised in experiments, I compare my results with those of experiments both qualitatively and by extending the equations for a single quantised vortex ring.

This dissertation considers how housing wealth impacts household behavior. The essays pay close attention to the borrowing collateral role of housing wealth, and address how changing house prices affect household spending. Chapter II of the dissertation investigates the relationship between house values and consumption. The chapter demonstrates that house values impact consumption by serving as borrowing collateral for households to finance and smooth their consumption. Changing house values have little effect, however, on the expenditures of households without apparent borrowing needs. In addition, the chapter shows that the impact of falling house prices on aggregate consumption is relatively small. Chapter III examines how households’ home equity extraction during 2001 to 2003 and 2003 to 2005 affects their spending and saving behavior. The chapter finds that a 1 dollar increase in equity extraction leads to 95 or 98 cent higher consumption expenditures. Nearly all of this spending increase is reversed in the subsequent period. Households who extract extract equity are somewhat more likely to pay down their higher cost credit card debt as well as invest in other real estate and businesses. Overall, the results in the chapter are consistent with households extracting equity to fund one-time durable good type consumption needs. The final chapter of this dissertation considers the theoretical relationship between collateralized borrowing and household consumption. The chapter examines households’ consumption decisions when they can borrow against their equity in an illiquid asset (house) to finance their consumption. This theoretical approach addresses questions that are not easily answered empirically such as whether household spending responds symmetrically to positive versus negative house price shocks. The paper finds that collateralized borrowing capacity acts as a partial hedge against future labor income risk. Indeed, households borrow to smooth their consumption somewhat in response to negative labor income shocks. In addition, the consumption growth responses to illiquid asset price shocks are relatively symmetric. Also, the impact of house price shocks on consumption is not large compared to income shocks.

Polar Spectrum Coding is a novel speech coding algorithm for narrowband voice communications. A polar Fourier transform of the signal is computed, and the magnitude and phase of the speech spectrum is encoded for transmission. The correlation between frames of speech signals is exploited to minimize the transmission rate required for intelligible speech. At the receiver, the encoded words are decoded and the spectrum reconstructed. An inverse Fourier transform is performed, and the result is the reconstructed speech waveform. Polar Spectrum Coding theory is explained. The sensitivities of various parameters on performance are explored, and performance in the presence of channel noise is measured. Directions for future research in the realm of Polar Spectrum Coding is suggested.