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Analyses of noncanonical DNA structures
The structural polymorphic nature of DNA has been long been recognized since the model of the right-handed B-DNA duplex proposed by James Watson and Francis Crick was accepted. Its malleability is thought to be critical in protein recognition and manipulation. In particular, it can form Holliday junctions, four-way DNA structural intermediates of homologous recombination mediated events in which four nucleic acid strands complex to give rise to double-helical arms extending from a central point. The variable recognition specificities of resolvases, a group of proteins that dissociate Holliday junctions into discrete duplexes, are addressed in this dissertation as related to the different structural conformations that can be adopted by junctions. We also describe an unusual base pair observed in the crystal structure of a Holliday junction. The wobbled adenine-thymine base pair can be best ascribed to the assumption of a rare tautomeric form by one of the bases. Such observation provides unique and physiologically relevant evidence for a rare
nucleotide base tautomerization, with profound biological and chemical implications that deserve further investigation.
Finally, the evolutionary emergence of another known DNA structure, the left-handed Z-DNA, is also studied along with three other GC-rich genomic elements. The possible functions of Z-DNA have only been recently elucidated though it was the first single-crystal X-ray structure of a DNA double helix. In our phylogenomic analysis of the genomes of sixteen organisms, ranging from cyanobacteria to complex eukaryotes, we offer new insights into its evolutionary emergence near the transcription start site. A model is derived which correlates its emergence with other transcriptional regulatory sequences and evolutionary gain of function. Thus, the studies presented in this thesis expand our knowledge of noncanonical DNA structures and provoke questions about their functions in the cell
Evaluation of one-step luminescent cyanoacrylate fuming
© 2016 Elsevier Ireland Ltd. One-step luminescent cyanoacrylates have recently been introduced as an alternative to the conventional cyanoacrylate fuming methods. These new techniques do not require the application of a luminescent post-treatment in order to enhance cyanoacrylate-developed fingermarks. In this study, three one-step polymer cyanoacrylates: CN Yellow Crystals (Aneval Inc.), PolyCyano UV (Foster + Freeman Ltd.) and PECA Multiband (BVDA), and one monomer cyanoacrylate: Lumikit™ (Crime Scene Technology), were evaluated against a conventional two-step cyanoacrylate fuming method (Cyanobloom (Foster + Freeman Ltd.) with rhodamine 6G stain). The manufacturers' recommended conditions or conditions compatible with the MVC™ 1000/D (Foster + Freeman Ltd.) were assessed with fingermarks aged for up to 8 weeks on non-porous and semi-porous substrates. Under white light, Cyanobloom generally gave better development than the one-step treatments across the substrates. Similarly when viewed under the respective luminescent conditions, Cyanobloom with rhodamine 6G stain resulted in improved contrast against the one-step treatments except on polystyrene, where PolyCyano UV and PECA Multiband gave better visualisation. Rhodamine 6G post-treatment of one-step samples did not significantly enhance the contrast of any of the one-step treatments against Cyanobloom/rhodamine 6G-treated samples
Nodular Fasciitis
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135180/1/jum2014334565.pd
The effect of motion adaptation on the position of elements in the visual saltation illusion.
The visual saltation illusionVillusory motion induced by presenting elements first to one peripheral location, then to another, in rapid and regular successionVbelongs to a class of stimuli for which a difference exists between the physical and perceived positions of elements. Rather than being perceived at their physical location, elements are perceived as traveling smoothly across the area between the two locations. In separate experiments, we examined the distortion to the saltatory path caused by adaptation to an upward drifting grating presented between the two physically stimulated locations (where elements were nonetheless perceived), and at the first location of physical stimulation. Where adaptation occurred between the two sites of physical stimulation, the saltatory path was distorted as if elements had a physical origin at that location; elements perceived as arising from the central location were subject to a motion aftereffect (MAE). Where motion adaptation overlapped the first site of physical stimulation, the saltatory path was affected only for those elements perceived as arising from the first location; elements perceived at the central location (but physically presented at the first site of stimulation) were not subject to an MAE. Our results indicate that the impact of motion adaptation on position is dependent on the perceived, and not the physical, location of elements
Local biases drive, but do not determine, the perception of illusory trajectories
When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception
Local biases drive, but do not determine, the perception of illusory trajectories
When a dot moves horizontally across a set of tilted lines of alternating orientations, the dot appears to be moving up and down along its trajectory. This perceptual phenomenon, known as the slalom illusion, reveals a mismatch between the veridical motion signals and the subjective percept of the motion trajectory, which has not been comprehensively explained. In the present study, we investigated the empirical boundaries of the slalom illusion using psychophysical methods. The phenomenon was found to occur both under conditions of smooth pursuit eye movements and constant fixation, and to be consistently amplified by intermittently occluding the dot trajectory. When the motion direction of the dot was not constant, however, the stimulus display did not elicit the expected illusory percept. These findings confirm that a local bias towards perpendicularity at the intersection points between the dot trajectory and the tilted lines cause the illusion, but also highlight that higher-level cortical processes are involved in interpreting and amplifying the biased local motion signals into a global illusion of trajectory perception
Optimising the glaucoma signal/noise ratio by mapping changes in spatial summation with area-modulated perimetric stimuli
Identification of glaucomatous damage and progression by perimetry are limited by measurement and response variability. This study tested the hypothesis that the glaucoma damage signal/noise ratio is greater with stimuli varying in area, either solely, or simultaneously with contrast, than with conventional stimuli varying in contrast only (Goldmann III, GIII). Thirty glaucoma patients and 20 age-similar healthy controls were tested with the Method of Constant Stimuli (MOCS). One stimulus modulated in area (A), one modulated in contrast within Ricco's area (C R ), one modulated in both area and contrast simultaneously (AC), and the reference stimulus was a GIII, modulating in contrast. Stimuli were presented on a common platform with a common scale (energy). A three-stage protocol minimised artefactual MOCS slope bias that can occur due to differences in psychometric function sampling between conditions. Threshold difference from age-matched normal (total deviation), response variability, and signal/noise ratio were compared between stimuli. Total deviation was greater with, and response variability less dependent on defect depth with A, AC, and C R stimuli, compared with GIII. Both A and AC stimuli showed a significantly greater signal/noise ratio than the GIII, indicating that area-modulated stimuli offer benefits over the GIII for identifying early glaucoma and measuring progression
On the Hydrogen Oxalate Binding Motifs onto Dinuclear Cu and Ag Metal Phosphine Complexes
We report the binding geometries of the isomers that are formed when the hydrogen oxalate ((CO)H=HO) anion attaches to dinuclear coinage metal phosphine complexes of the form [MMdcpm(HOx)] with M=Cu, Ag and dcpm=bis(dicyclohexylphosphino)methane, abbreviated [MM]. These structures are established by comparison of isomer-selective experimental vibrational band patterns displayed by the cryogenically cooled and N-tagged cations with DFT calculations of the predicted spectra for various local minima. Two isomeric classes are identified that feature either attachment of the carboxylate oxygen atoms to the two metal centers (end-on docking) or attachment of oxygen atoms on different carbon atoms asymmetrically to the metal ions (side-on docking). Within each class, there are additional isomeric variations according to the orientation of the OH group. This behavior indicates that HOx undergoes strong and directional coordination to [CuCu] but adopts a more flexible coordination to [AgAg]. Infrared spectra of the bare ions, fragmentation thresholds and ion mobility measurements are reported to explore the behaviors of the complexes at ambient temperature
Treating inborn errors of liver metabolism with stem cells: current clinical development
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