Distal renal tubular acidosis developments in its diagnosis and pathophysiology

This thesis describes two groups of experiments, both relating to the condition of distal renal tubular acidosis (dRTA). In the first, an alternative diagnostic test of dRTA to the ‘gold standard’ short ammonium chloride (NH4Cl) test was assessed. This was achieved by the simultaneous oral administration of the diuretic furosemide and the mineralocorticoid fludrocortisone to increase distal sodium delivery and a-intercalated cell proton secretion. I evaluated 11 control subjects and 10 patients with known dRTA by giving oral NH4Cl or furosemide/fludrocortisone in random order on separate days. 3 subjects were unable to complete the study due to vomiting after the NH4Cl, however there were no adverse effects with furosemide/fludrocortisone administration. The urine pH decreased to less than 5.3 in the controls with both tests, whereas no patients were able to lower their urine pH below 5.3 with either test. The simultaneous administration of furosemide/fludrocortisone proved to be an easy, effective and well-tolerated alternative to the standard NH4Cl test for the diagnosis of dRTA. The second group were laboratory-based molecular physiology experiments. Anion exchanger 1 (AE1) mediates electroneutral anion exchange across cell membranes. It is the most abundant protein in the red cell membrane, but is also found in the basolateral membrane of renal a-intercalated cells, where it is required for urinary acidification. Point mutations have been described that convert the red cell AE1 into a cation conductance. AE1 mutations can also cause hereditary dRTA. I investigated the properties of four dRTA associated AE1 mutations (R586H, G609R, S613F and G701D) by heterologous expression in Xenopus Laevis oocytes. These mutants proved to be functional anion exchangers, unlike the red cell mutants, but also demonstrated a cation ‘leak’. I found a very large leak property in the G701D mutant, which is prevalent in SE Asia. I hypothesised that this property might confer a survival advantage. I characterised three other AR dRTA-associated AE1 mutants found in SE Asia, S773P, \Delta850 and A858D via similar transport experiments in AE1-expressing Xenopus oocytes. These three SE Asian mutants also had cation leaks of similar magnitude to that seen in G701D, a property that distinguishes them as a discrete group. The clustering of these cation-leaky AE1 mutations to malarious areas of SE Asia suggests that they may confer malaria resistance

How does the substrate affect the Raman and excited state spectra of a carbon nanotube?

We study the optical properties of a single, semiconducting single-walled carbon nanotube (CNT) that is partially suspended across a trench and partially supported by a SiO2-substrate. By tuning the laser excitation energy across the E33 excitonic resonance of the suspended CNT segment, the scattering intensities of the principal Raman transitions, the radial breathing mode (RBM), the G-mode and the D-mode show strong resonance enhancement of up to three orders of magnitude. In the supported part of the CNT, despite a loss of Raman scattering intensity of up to two orders of magnitude, we recover the E33 excitonic resonance suffering a substrate-induced red shift of 50 meV. The peak intensity ratio between G-band and D-band is highly sensitive to the presence of the substrate and varies by one order of magnitude, demonstrating the much higher defect density in the supported CNT segments. By comparing the E33 resonance spectra measured by Raman excitation spectroscopy and photoluminescence (PL) excitation spectroscopy in the suspended CNT segment, we observe that the peak energy in the PL excitation spectrum is red-shifted by 40 meV. This shift is associated with the energy difference between the localized exciton dominating the PL excitation spectrum and the free exciton giving rise to the Raman excitation spectrum. High-resolution Raman spectra reveal substrate-induced symmetry breaking, as evidenced by the appearance of additional peaks in the strongly broadened Raman G band. Laser-induced line shifts of RBM and G band measured on the suspended CNT segment are both linear as a function of the laser excitation power. Stokes/anti-Stokes measurements, however, reveal an increase of the G phonon population while the RBM phonon population is rather independent of the laser excitation power.Comment: Revised manuscript, 20 pages, 8 figure

Snacking, sugar-sweetened beverage consumption and child obesity in low-income households

Purpose: Snacking contributes to one-quarter of children’s total daily energy intake in the USA, with many snack foods being nutrient-poor and energy-dense. Snacking and sugary beverage consumption have been identified as potential contributors to childhood overweight and obesity and may play a particularly important role among children from socioeconomically disadvantaged households that generally display higher rates of obesity. This exploratory study investigated associations between consumption of snack foods, sugar-sweetened beverages (SSB) and overweight and obesity in children from low-income households. Design/methodology/approach: Data from households that participated in a multi-state cost-offset (CO-CSA) community supported agriculture intervention in 2016 and 2017 (n = 305) were analyzed. Fixed effect regression models were used to estimate associations between child monthly consumption of salty snack foods; sweet snack foods and SSBs; and child weight status, accounting for demographic characteristics. Findings: No associations were found between snack or SSB consumption and child overweight. However, household income was significantly, negatively related to all three consumption variables (Salty snacks: ß = −0.09, SE = 0.04, p = 0.02; Sweet snacks: ß= −0.10, SE = 0.04, p = 0.01; SSB: ß= −0.21, SE = 0.05, p = 0.0001). The results suggest that household income may play an important role in children’s snacking and SSB behaviors among more disadvantaged households. Practical implications: Factors beyond snack food and SSB consumption should be explored to better understand childhood overweight and obesity, and to inform future obesity interventions. Originality/value: Socioeconomic disparities in childhood obesity are an ongoing policy-relevant issue within the USA and internationally. This study provides new information about child snacking behaviors in a unique, low-income population and contributes to the evidence base regarding the role household context in shaping child consumption behaviors

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

First-Principles Study of Magnetic Properties of 3dTransition Metals Doped in ZnO Nanowires

The defect formation energies of transition metals (Cr, Fe, and Ni) doped in the pseudo-H passivated ZnO nanowires and bulk are systematically investigated using first-principles methods. The general chemical trends of the nanowires are similar to those of the bulk. We also show that the formation energy increases as the diameter of the nanowire decreases, indicating that the doping of magnetic ions in the ZnO nanowire becomes more difficult with decreasing diameter. We also systematically calculate the ferromagnetic properties of transition metals doped in the ZnO nanowire and bulk, and find that Cr ions of the nanowire favor ferromagnetic state, which is consistent with the experimental results. We also find that the ferromagnetic coupling state of Cr is more stable in the nanowire than in the bulk, which may lead to a higherTcuseful for the nano-materials design of spintronics

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change