Trans-ethnic fine mapping highlights kidney-function genes linked to salt sensitivity

We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

THE PRICE SENSITIVITY OF DEMAND FOR HIGHER EDUCATION AMONG NON-TRADITIONAL STUDENTS

This dissertation examines the price sensitivity of demand for higher education among non-traditional students in the United States. Chapter 1 discusses the issues related to the demand for higher education. It presents the recent trends and reviews the literature addressing these issues. A major conclusion that emerges from this chapter is that the price sensitivity of demand for higher education appears to depend on the source of the variation in price and the characteristics of the students who face the price change. The baseline estimate for the price sensitivity of demand is that a $1,000 (in year 2000 dollars) decrease in tuition costs should result in a 4 percentage-point increase in enrollment for the traditional 18- to 24-year-old student. Chapter 2 examines the price sensitivity of demand for higher education for military spouses resulting from variation in tuition due to military-mandated moves across states. The data suggest that a $1,000 (in year 2000 dollars) decrease in the cost of 2-year schools is associated with a 1--1.5 percentage-point increase in the probability of attending college. This estimate is less than half the previous estimates due to in-state tuition price differences faced by the civilian 18- to 24-year-old population on a percentage-point basis. However, this represents a 7--10 percent increase for this population, and the magnitude of this metric is in line with previous estimates. This suggests tuition assistance can be an effective means of increasing enrollment for military spouses, but other barriers to education for this population may also need to be addressed. Chapter 3 examines the impact of a change in the tax treatment of savings set aside for higher education by those who decide to suspend their education and enter the workforce. The taxation of these funds appears to have increased the rate at which these funds are included in an employee's initial contract and the quantity of funds allocated. These results are counterintuitive if the tax preference was the primary reason for the savings plan. However, these results suggest the rationale for the savings plan was to offer targeted additional compensation to recruits with greater negotiating power. Taxation of funds previously set aside did not appear to have a statistically significant impact on their utilization. Point estimates of the price sensitivity of demand from changes in the out-of-pocket costs for higher education induced by the taxation of these funds were small and often not statistically significant. The results from this dissertation show responses to changes in the net cost of college that differ by the source of price variation and the population experiencing them. This is consistent with the previous literature. This dissertation contributes to the literature by providing estimates for the price sensitivity of demand for higher education to previously understudied non-traditional students.

A revised L-band radio-brightness sensitivity to extreme winds under tropical cyclones: The 5 year SMOS-Storm database

Five years of SMOS L-band brightness temperature data intercepting a large number of tropical cyclones (TCs) are analyzed. The storm-induced half-power radio-brightness contrast (ΔI) is defined as the difference between the brightness observed at a specific wind force and that for a smooth water surface with the same physical parameters. ΔI can be related to surface wind speed and has been estimated for ~ 300 TCs that intercept with SMOS measurements. ΔI, expressed in a common storm-centric coordinate system, shows that mean brightness contrast monotonically increases with increased storm intensity ranging from ~ 5 K for strong storms to ~ 24 K for the most intense Category 5 TCs. A remarkable feature of the 2D mean ΔI fields and their variability is that maxima are systematically found on the right quadrants of the storms in the storm-centered coordinate frame, consistent with the reported asymmetric structure of the wind and wave fields in hurricanes. These results highlight the strong potential of SMOS measurements to improve monitoring of TC intensification and evolution. An improved empirical geophysical model function (GMF) was derived using a large ensemble of co-located SMOS ΔI, aircraft and H*WIND (a multi-measurement analysis) surface wind speed data. The GMF reveals a quadratic relationship between ΔI and the surface wind speed at a height of 10 m (U10). ECMWF and NCEP analysis products and SMOS derived wind speed estimates are compared to a large ensemble of H*WIND 2D fields. This analysis confirms that the surface wind speed in TCs can effectively be retrieved from SMOS data with an RMS error on the order of 10 kt up to 100 kt. SMOS wind speed products above hurricane force (64 kt) are found to be more accurate than those derived from NWP analyses products that systematically underestimate the surface wind speed in these extreme conditions. Using co-located estimates of rain rate, we show that the L-band radio-brightness contrasts could be weakly affected by rain or ice-phase clouds and further work is required to refine the GMF in this context.

Raman microscopy of formamide-intercalated kaolinites treated by controlled-rate thermal analysis technology

Raman spectroscopy of formamide-intercalated kaolinites treated using controlled-rate thermal analysis technology (CRTA), allowing the separation of adsorbed formamide from intercalated formamide in formamide-intercalated kaolinites, is reported. The Raman spectra of the CRTA-treated formamide-intercalated kaolinites are significantly different from those of the intercalated kaolinites, which display a combination of both intercalated and adsorbed formamide. An intense band is observed at 3629 cm-1, attributed to the inner surface hydroxyls hydrogen bonded to the formamide. Broad bands are observed at 3600 and 3639 cm-1, assigned to the inner surface hydroxyls, which are hydrogen bonded to the adsorbed water molecules. The hydroxyl-stretching band of the inner hydroxyl is observed at 3621 cm-1 in the Raman spectra of the CRTA-treated formamide-intercalated kaolinites. The results of thermal analysis show that the amount of intercalated formamide between the kaolinite layers is independent of the presence of water. Significant differences are observed in the CO stretching region between the adsorbed and intercalated formamide.

Hydrazine-hydrate intercalated halloysite under controlled-rate thermal analysis conditions

The thermal behaviour of halloysite fully expanded with hydrazine-hydrate has been investigated in nitrogen atmosphere under dynamic heating and at a constant, pre-set decomposition rate of 0.15 mg min-1. Under controlled-rate thermal analysis (CRTA) conditions it was possible to resolve the closely overlapping decomposition stages and to distinguish between adsorbed and bonded reagent. Three types of bonded reagent could be identified. The loosely bonded reagent amounting to 0.20 mol hydrazine-hydrate per mol inner surface hydroxyl is connected to the internal and external surfaces of the expanded mineral and is present as a space filler between the sheets of the delaminated mineral. The strongly bonded (intercalated) hydrazine-hydrate is connected to the kaolinite inner surface OH groups by the formation of hydrogen bonds. Based on the thermoanalytical results two different types of bonded reagent could be distinguished in the complex. Type 1 reagent (approx. 0.06 mol hydrazine-hydrate/mol inner surface OH) is liberated between 77 and 103°C. Type 2 reagent is lost between 103 and 227°C, corresponding to a quantity of 0.36 mol hydrazine/mol inner surface OH. When heating the complex to 77°C under CRTA conditions a new reflection appears in the XRD pattern with a d-value of 9.6 Å, in addition to the 10.2 Ĺ reflection. This new reflection disappears in contact with moist air and the complex re-expands to the original d-value of 10.2 Å in a few h. The appearance of the 9.6 Å reflection is interpreted as the expansion of kaolinite with hydrazine alone, while the 10.2 Å one is due to expansion with hydrazine-hydrate. FTIR (DRIFT) spectroscopic results showed that the treated mineral after intercalation/deintercalation and heat treatment to 300°C is slightly more ordered than the original (untreated) clay.