EDoF-ToF: extended depth of field time-of-flight imaging.

Conventional continuous-wave amplitude-modulated time-of-flight (CWAM ToF) cameras suffer from a fundamental trade-off between light throughput and depth of field (DoF): a larger lens aperture allows more light collection but suffers from significantly lower DoF. However, both high light throughput, which increases signal-to-noise ratio, and a wide DoF, which enlarges the system's applicable depth range, are valuable for CWAM ToF applications. In this work, we propose EDoF-ToF, an algorithmic method to extend the DoF of large-aperture CWAM ToF cameras by using a neural network to deblur objects outside of the lens's narrow focal region and thus produce an all-in-focus measurement. A key component of our work is the proposed large-aperture ToF training data simulator, which models the depth-dependent blurs and partial occlusions caused by such apertures. Contrary to conventional image deblurring where the blur model is typically linear, ToF depth maps are nonlinear functions of scene intensities, resulting in a nonlinear blur model that we also derive for our simulator. Unlike extended DoF for conventional photography where depth information needs to be encoded (or made depth-invariant) using additional hardware (phase masks, focal sweeping, etc.), ToF sensor measurements naturally encode depth information, allowing a completely software solution to extended DoF. We experimentally demonstrate EDoF-ToF increasing the DoF of a conventional ToF system by 3.6 ×, effectively achieving the DoF of a smaller lens aperture that allows 22.1 × less light. Ultimately, EDoF-ToF enables CWAM ToF cameras to enjoy the benefits of both high light throughput and a wide DoF.

Fumarase affects the deoxyribonucleic acid damage response by protecting the mitochondrial desulfurase Nfs1p from modification and inactivation.

The Krebs cycle enzyme fumarase, which has been identified as a tumor suppressor, is involved in the deoxyribonucleic acid (DNA) damage response (DDR) in human, yeast, and bacterial cells. We have found that the overexpression of the cysteine desulfurase Nfs1p restores DNA repair in fumarase-deficient yeast cells. Nfs1p accumulates inactivating post-translational modifications in yeast cells lacking fumarase under conditions of DNA damage. Our model is that in addition to metabolic signaling of the DDR in the nucleus, fumarase affects the DDR by protecting the desulfurase Nfs1p in mitochondria from modification and inactivation. Fumarase performs this protection by directly binding to Nfs1p in mitochondria and enabling, the maintenance, via metabolism, of a non-oxidizing environment in mitochondria. Nfs1p is required for the formation of Fe-S clusters, which are essential cofactors for DNA repair enzymes. Thus, we propose that the overexpression of Nfs1p overcomes the lack of fumarase by enhancing the activity of DNA repair enzymes.

Post-translational Modifications of Fumarase Regulate its Enzyme Activity and Function in Respiration and the DNA Damage Response.

The Krebs cycle enzyme fumarase is a dual-targeted protein that is located in the mitochondria and cytoplasm of eukaryotic cells. Besides being involved in the TCA cycle and primary metabolism, fumarase is a tumour suppressor that aids DNA repair in human cells. Using mass spectrometry, we identified modifications in peptides of cytosolic yeast fumarase, some of which were absent when the cells were exposed to DNA damage (using the homing endonuclease system or hydroxyurea). We show that DNA damage increased the enzymatic activity of fumarase, which we hypothesized to be affected by post-translational modifications. Succinylation and ubiquitination of fumarase at lysines 78 and 79, phosphorylation at threonine 122, serine 124 and threonine 126 as well as deamidation at arginine 239 were found to be functionally relevant. Upon homology analysis, these residues were also found to be evolutionally conserved. Serine 128, on the other hand, is not evolutionary conserved and the Fum1S128D phosphorylation mimic was able to aid DNA repair. Our molecular model is that the above modifications inhibit the enzymatic activity of cytosolic fumarase under conditions of no DNA damage induction and when there is less need for the enzyme. Upon genotoxic stress, some fumarase modifications are removed and some enzymes are degraded while unmodified proteins are synthesized. This report is the first to demonstrate how post-translational modifications influence the catalytic and DNA repair functions of fumarase in the cell.