Aspects of the biogenesis of cytochrome c oxidase in human cells

Cytochrome c oxidase (COX) is a component of the mitochondrial oxidative phosphorylation system (OXPHOS) which is the principal source of ATP for the majority of human tissues. The COX holo-complex is a homodimer of 13 different subunits, encoded by both the nuclear and mitochondrial genomes (mtDNA), and contains metal ions and haem A prosthetic groups. Disrupted biogenesis of the holo-complex is the most common cause of COX deficiency. As genetic manipulation of human cells is difficult, cells derived from patients with COX deficiency provide a valuable resource for improving our understanding of COX biogenesis and COX deficiency. This thesis is a comparative study of COX deficient fibroblasts derived from seven patients with mitochondrial disorders of undetermined genetic origin, normal controls and disease controls carrying mutations in mitochondrial tRNA genes or the COX assembly factors SCO1 and COX10. The project was designed to answer two questions: What are the molecular mechanisms behind the enzyme deficiency in the patient cells What can this tell us about the biogenesis of the COX holo-complex Phenotyping of the cultures revealed distinct patterns of OXPHOS subunit expression and confirmed that the COX defects were caused by disrupted biogenesis of the holo-complex. Genotyping excluded the involvement of mtDNA and sequencing of the COX assembly factor SURF1 identified mutations in four of the patients. Blue-native polyacrylamide gel electrophoresis found that COX sub-complexes, which resembled known assembly intermediates, accumulated in SURF1 and SCO1 mutant cells but not those with COX10 mutations. This suggests that SURF1 and SCO1 function at a similar point in COX biogenesis and supports the view that COX10 functions early in COX assembly. The results are discussed in the context of our current understanding of COX biogenesis and the causes of COX deficiency with emphasis on the molecular pathology of SURF1 mutant cells

Shortest Path Computation with No Information Leakage

Shortest path computation is one of the most common queries in location-based services (LBSs). Although particularly useful, such queries raise serious privacy concerns. Exposing to a (potentially untrusted) LBS the client's position and her destination may reveal personal information, such as social habits, health condition, shopping preferences, lifestyle choices, etc. The only existing method for privacy-preserving shortest path computation follows the obfuscation paradigm; it prevents the LBS from inferring the source and destination of the query with a probability higher than a threshold. This implies, however, that the LBS still deduces some information (albeit not exact) about the client's location and her destination. In this paper we aim at strong privacy, where the adversary learns nothing about the shortest path query. We achieve this via established private information retrieval techniques, which we treat as black-box building blocks. Experiments on real, large-scale road networks assess the practicality of our schemes.Comment: VLDB201

HST Images Flash Ionization of Old Ejecta by the 2011 Eruption of Recurrent Nova T Pyxidis

T Pyxidis is the only recurrent nova surrounded by knots of material ejected in previous outbursts. Following the eruption that began on 2011 April 14.29, we obtained seven epochs (from 4 to 383 days after eruption) of Hubble Space Telescope narrowband Ha images of T Pyx . The flash of radiation from the nova event had no effect on the ejecta until at least 55 days after the eruption began. Photoionization of hydrogen located north and south of the central star was seen 132 days after the beginning of the eruption. That hydrogen recombined in the following 51 days, allowing us to determine a hydrogen atom density of at least 7e5 cm^-3 - at least an order of magnitude denser than the previously detected, unresolved [NII] knots surrounding T Pyx. Material to the northwest and southeast was photoionized between 132 and 183 days after the eruption began. 99 days later that hydrogen had recombined. Both then (282 days after outburst) and 101 days later, we detected almost no trace of hydrogen emission around T Pyx. There is a large reservoir of previously unseen, cold diffuse hydrogen overlapping the previously detected, [NII] - emitting knots of T Pyx ejecta. The mass of this newly detected hydrogen is probably an order of magnitude larger than that of the [NII] knots. We also determine that there is no significant reservoir of undetected ejecta from the outer boundaries of the previously detected ejecta out to about twice that distance, near the plane of the sky. The lack of distant ejecta is consistent with the Schaefer et al (2010) scenario for T Pyx, in which the star underwent its first eruption within five years of 1866 after many millennia of quiescence, followed by the six observed recurrent nova eruptions since 1890. This lack of distant ejecta is not consistent with scenarios in which T Pyx has been erupting continuously as a recurrent nova for many centuries or millennia.Comment: 27 pages, 10 figures, submitted to the Astrophysical Journa

Ultraviolet observations of LMC nova 1988

The IUE obtained ultraviolet spectra of a nova in an external galaxy. The spectral features do not seem unusual for a nova at maximum but it is hoped to be able to follow it for a long enough time to be able to study the high ionization lines that appear when the density drops to lower values (the nebular stage). A high dispersion spectrum was also obtained to assist in the line identification and to study the line of sight to the LMC 1 deg of arc away from SN 1987A

The Merger Rate of Binary White Dwarfs in the Galactic Disk

We use multi-epoch spectroscopy of about 4000 white dwarfs in the Sloan Digital Sky Survey to constrain the properties of the Galactic population of binary white dwarf systems and calculate their merger rate. With a Monte Carlo code, we model the distribution of DRVmax, the maximum radial velocity shift between exposures of the same star, as a function of the binary fraction within 0.05 AU, fbin, and the power-law index in the separation distribution at the end of the common envelope phase, alpha. Although there is some degeneracy between fbin and alpha, the the fifteen high DRVmax systems that we find constrain the combination of these parameters, which determines a white dwarf merger rate per unit stellar mass of 1.4(+3.4,-1.0)e-13 /yr/Msun (1-sigma limits). This is remarkably similar to the measured rate of Type Ia supernovae per unit stellar mass in Milky-Way-like Sbc galaxies. The rate of super-Chandrasekhar mergers is only 1.0(+1.6,-0.6)e-14 /yr/Msun. We conclude that there are not enough close binary white dwarf systems to reproduce the observed Type Ia SN rate in the 'classic' double degenerate super-Chandrasekhar scenario. On the other hand, if sub-Chandrasekhar mergers can lead to Type Ia SNe, as recently suggested by some studies, they could make a major contribution to the overall Type Ia SN rate. Although unlikely, we cannot rule out contamination of our sample by M-dwarf binaries or non-Gaussian errors. These issues will be clarified in the near future by completing the follow-up of all 15 high DRVmax systems.Comment: 5 pages, 3 figures, 1 table, ApJL, accepted (modified abstract, this version should match the published one