Browsing by Subject "Structure"
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Item From structure and dynamics to novel therapeutic development for muscular dystrophy.(2012-07) Lin, Ava YunDystrophin is defective in Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are debilitating X-linked diseases that currently have no cure. Dystrophin links the actin cytoskeleton at its N-terminus and a glycoprotein complex (DGC) embedded in the sarcolemma at its C-terminus, apparently providing mechanical stability to the muscle during contraction. Due to the large size (427 kD) and filamentous nature of dystrophin, studies of its function and attempts to develop effective therapeutics have developed slowly, despite intensive efforts. Utrophin (395 kD) is a homolog of dystrophin that has shown therapeutic promise in mdx mice, which lack dystrophin. Utrophin is endogenously expressed in the cytoskeleton of fetal and developing muscle but is replaced by dystrophin as the muscle matures (8-10). Both dystrophin and utrophin belong to the spectrin superfamily of actin-binding proteins, which carry out diverse functions in the cytoskeleton of most cells. Of the many proteins included in this superfamily, dystrophin and utrophin are among the least studied in terms of structural dynamics, limiting the understanding of their function at the sarcolemma. In order to target the root of dystrophin malfunction in muscular dystrophy, we need to better understand the native functions of dystrophin and utrophin. Lack of structural information about dystrophin and its interactions adds to the complexity of tying clinical presentations to the diverse disease-causing mutations, and hinders therapeutic advancement in gene or drug therapy. There are numerous mouse-model studies, but there are varied results across several parameters tested, and no construct or drug has been found that restores normal muscle force in the mdx mouse. Exon-skipping morpholinos are expensive to produce with variable delivery and efficacy to muscle groups and require a customized oligo design for each mutation, making it difficult to test them individually in mouse models. In order to (a) understand disease mechanisms and (b) design better therapies rationally, we need more fundamental information about the structures and interactions of specific regions of dystrophin and utrophin. That is the goal of this project.Item Full-depth precast concrete bridge deck system: phase II(2012-11) Halverson, MaxThe Minnesota Department of Transportation (MnDOT) developed a design for a precast composite slab span system (PCSSS) to be used in accelerated bridge construction. The system consists of shallow inverted-tee precast beams placed between supports with cast-in-place (CIP) concrete placed on top, forming a composite slab span system. Suitable for spans between 20 and 60 ft., the MnDOT PCSSS is useful for replacing a large number of aging conventional slab-span bridges throughout the United States highway system. Originally developed in 2005, the PCSSS had three distinct design generations in the 12 bridges that were constructed by MnDOT between 2005 and 2011. The objective of this investigation was to evaluate the field performance of a sample of the existing bridges through detailed crack mapping and core analysis and through continued monitoring of data obtained from one of the original PCSSS bridges (Bridge No. 13004) instrumented during construction in 2005. A parametric design study was also conducted to investigate the effects of continuity design on the economy of the PCSSS. Five of the 12 PCSSS bridges, constructed between 2005 and 2011, were selected as the sample set to conduct detailed surveys of surface cracking and examinations of extracted core specimens to evaluate effects of the design changes. Surface cracking was recorded over three different inspections between the fall of 2009 and the summer of 2011. Each inspection was done using a systematic procedure of documenting crack locations and measuring crack widths. The result was a series of crack maps for each bridge, showing the surface cracking compared to major design features. Different line types were used to distinguish relative crack widths. Core specimens were taken from each of the five inspected bridges based on anticipated reflective crack locations. The cores were partial depth through the CIP concrete, taken over either the longitudinal joint between precast panels or over the precast web corner. Each core was examined under a digital microscope for cracking with particular attention paid to the regions above the longitudinal joints and web corners. The results of the core investigation were compared to the corresponding crack maps. Overall, the field inspections indicated that the changes made between each design generation improved the performance of the PCSSS. Bridge No. 13004 in Center City, MN from the first design generation showed many short, longitudinal cracks on the deck surface with very little transverse and map cracking. The longitudinal cracks were located primarily over the precast beam web, corresponding to what appeared to be insufficient consolidation of the CIP concrete around the stirrups projecting vertically from the section to facilitate composite action, which had little clearance above the precast webs. In the second generation, more clearance was provided under the stirrups projecting from the surface. Bridge Nos. 33005 and 33008 near Mora, MN from the second generation did not show the short cracks over the webs from the first generation, but more transverse cracks and longer longitudinal cracks were observed. Bridge No. 33008 showed significantly more longitudinal cracking than any of the other bridges. Significant longitudinal cracks were noted along several joints between the precast beams. Core specimens showed that these cracks were full-depth reflective cracks. The only other bridge to show reflective cracking from the core specimens was Bridge No. 13004, but these were not full-depth cracks. It was unclear from the design details of Bridge No. 33008 why it was in worse condition than the other bridges. This bridge also had noticeably different cambers between adjacent beams observed from the underside of the bridge, although it was unclear how this might be associated with the observed longitudinal cracking. For the third design generation, the thickness of the precast beam flanges was decreased and the trough reinforcement spacing (consisting of trough hooks projecting horizontally from the beams across the joint, as well as a drop-in cage) was decreased from a maximum 10 in. center-to-center to 6 in. center-to-center to better control reflective cracking. The decreased spacing was accomplished by staggering the trough hooks from adjacent precast beams. Bridge Nos. 49007 and 49036 near Little Falls, MN from the third generation did not exhibit longitudinal cracking over the precast beam joints, indicating that the design changes may have had a positive impact, though not conclusively. The most significant issue observed with the third generation was shrinkage cracking, indicated by longitudinal cracks located over the precast beam webs and more extensive transverse and map cracking. Generally, bridges with a larger length to width aspect ratio (i.e., L/W) had more transverse cracking, which could be related to more longitudinal shrinkage restraint. In addition to the field inspections, strain data from the instrumentation of Bridge No. 13004 was analyzed to evaluate performance. The bridge was instrumented in 2005 to monitor reflective cracking and continuous system behavior. Six years of strain and temperature data showed a progression of reflective cracking in several locations and significant cracking due to thermally induced restraint moments. The reflective cracking from the strain data was confirmed by observed cracks in the core specimens near the locations of the strain gauges. While the width of the reflective cracks appeared to increase over time from the strain measurements, the measurements began to plateau by the end of the six-year monitoring period. Restraint moment cracking was indicated by strain gauges attached to continuity connection reinforcement. The measured restraint moment strains were large enough for fatigue to be of potential concern, although the strains were associated with environmental effects which have a low number of cycles at once per day. Measured strains associated with both reflective cracking and restraint moments were primarily driven by seasonal and daily temperature variations, highlighting the important role of thermal effects in design. Besides the detailed field investigations, a parametric study of PCSSS designs was conducted to determine whether there was an economic benefit of continuous system design. In particular, design implications of time-dependent and thermal gradient restraint moments and their effects on continuity were studied. Because the PCSSS is a simple-span system made continuous with a CIP deck, the effects of restraint moments must be considered in the design of continuous systems. The restraint moments are those that arise from continuity, or end restraint, over the piers due to beam creep, differential shrinkage between the CIP deck and beam, and thermal gradient. Restraint moments would not develop if PCSSS were built as a series of simple spans with no continuity provided between the spans. Eight bridges covering the feasible range of span configurations were designed as both simple and continuous systems. Flexural design was performed for each case, resulting in optimized precast sections within practical design constraints. Primary design parameters were strand number, section depth, and precast concrete strength. These design parameters were compared between the continuous and simple-span designs for each configuration to evaluate economic benefit. Generally, continuous PCSSS designs were equally or less economical than simple-span designs. Spans less than 30 feet had a slight economic benefit with continuous design because large restraint moments did not develop. However, spans greater than 30 feet developed large restraint moments in continuous design, particularly due to thermal gradient effects. In addition, the restraint moments greatly reduced continuity, effectively negating the benefit to live-load capacity. It was recommended that the PCSSS be designed as a simply-supported system for live load. Furthermore, because most continuous system designs were less economical than the corresponding simply-supported designs, it was concluded that designing the PCSSS as simply-supported while also including a continuity connection would be unconservative without accounting for restraint moments. A simple method was developed to account for restraint moments for this case without time-intensive calculations. Further recommendations related to the analysis of negative moments over PCSSS bridge piers were also provided. A review of current design methods and details concluded that the current PCSSS design was generally sufficient, and recommendations for future PCSSS designs were provided. Items reviewed were related to shrinkage restraint, reflective crack control, composite action, and defining tolerances for the PCSSS. In order to try to better control top surface deck cracking, recommendations included increasing the transverse reinforcement in the CIP deck to provide a gross reinforcement ratio, ρg, of 0.0063 with a spacing no greater than 9 in., based on the work of Frosch (2006). This would translate to increasing the current transverse deck reinforcement from No. 4 bars at 6 in. (ρg =0.0056) to No. 5 bars at 6 in. (ρg =0.0086) or No. 5 bars at an increased spacing of 8 in. (ρg =0.0065) to provide the needed volumetric ratio while maintaining the maximum spacing for surface crack control. The recommendations of NCHRP 10-71 for reinforcement in the trough are adopted in order to control reflective cracking In addition, it was recommended that composite action stirrups need not be used if the required shear stress transferred between the CIP concrete deck and precast beam is less than 135 psi.Item Metal structures for photonics and plasmonics(2013-07) Park, Jong HyukThe goal of this thesis is to investigate metal structures for photonics and plasmonics and to provide theoretical and experimental bases for their practical applications. Engineered micro- and nanostructures of a metal can efficiently manipulate surface plasmon polaritons (SPPs) - coupled photon-electron waves propagating along a metal-dielectric interface. Since SPPs are able to contain both characteristics of light and charge, exploiting SPPs can lead to novel optical behaviors, for example, concentration of light below the optical diffraction limit, generating large electric-field enhancements in confined regions. This unique characteristic of SPPs has opened up new opportunities for photonic and plasmonic applications such as surface-enhanced spectroscopy, subwavelength waveguides, optical antennas, solar cells, and thermophotovoltaics. However, while many fabrication techniques have been developed and utilized to prepare metal structures, some applications would still benefit from improved methods because SPPs are extremely sensitive to inhomogeneities on a metallic surface arising from roughness, impurities and even grain boundaries of a metal. To minimize the surface inhomogeneities of the metal structures and thus to exploit SPPs effectively, we introduced novel fabrication methods. First, the template-stripping method was employed to obtain high-quality silver films for SPPs in the visible wavelengths. The template-stripped films showed very smooth surfaces, leading to the improved dielectric function with high electrical conductivity and low optical loss. The dielectric function of the template-stripped films was compared with that of conventional films. As a result, the relation between the surface roughness and dielectric function of metal films could be derived. As another approach to reduce the inhomogeneities on a metal surface, we prepared single-crystalline silver films via epitaxial growth. Under controlled deposition conditions, single-crystalline silver films exhibited ultrasmooth surfaces with a root mean square roughness of 0.2 nm. Moreover, we observed that the absence of the grain boundaries can lead to an increase in SPP propagation length as well as precise patterning for metal structures. Beyond noble metals, we then introduced an effective route to obtain smooth patterned structures of refractory metals, semiconductors, and oxides via template stripping. The smooth structures of such materials can be favorable for many applications including thermal emitters, metamaterials, solar absorbers, and photovoltaics. We demonstrated that a variety of desired materials deposited on a thin noble metal layer can be peeled from silicon templates. After removing the noble metal layer, the revealed surfaces had very small roughness. This approach could easily reproduce structures via reuse of templates, leading to a low-cost and high-throughput process in micro- and nanofabrication. Finally, we showed that thermal excitation of SPPs in patterned metallic structures can provide tailored thermal emission. Typically, SPPs on metal structures are generated by using an optical source and then re-radiated as light, of which the emission angle and wavelength are determined by the geometry of the metal structures. However, since thermal energy can be another excitation source to create SPPs, heating of properly designed metal structures can result in tailored thermal emission. We experimentally demonstrated that at high temperatures, tungsten films with bull's-eye patterns exhibit tailored thermal emission with a unidirectional and monochromatic beam. In addition, since the thermal stability of the structures could be enhanced by coating with a protective oxide layer on the metal surface, the bull's-eye structures can be utilized as a novel radiation source. Overall, we pursued efficient engineering of SPPs in metal structures and development of improved fabrication methods for the metal structures. We believe that these results will promote the practical application of SPPs for electronic, photonic and plasmonic devices.Item Microtubule Sub-Structure and its Role in Protein Binding(2018-07) Reid, TaylorMicrotubules are structural polymers that participate in a wide range of cellular functions. The microtubule binding protein EB1 localizes to the growing ends of microtubules, where it facilitates interactions of key cellular proteins with the microtubule plus-end. Recent work has demonstrated that microtubule plus-ends have open, tapered conformations, which diverge greatly from a closed tube conformation. Thus, in this work we explored whether microtubule structure could impact the binding of EB1 to microtubules. Using quantitative fluorescence and electron microcopy experiments, we found that EB1 preferentially binds structurally disrupted or open structural features of microtubules as compared to the closed microtubule lattice. In corresponding 3D single- molecule diffusion simulations, a 70-fold rise in EB1 on-rates to tapered microtubule tip structures was observed relative to a closed lattice conformation, due to a high steric hindrance barrier that impedes EB1 from binding in its four-tubulin pocket-like lattice site, with greatly increased accessibility on two-tubulin protofilament edges at tapered microtubule ends. Thus, EB1’s four-tubulin pocket-like binding site on the microtubule leads to microtubule structural recognition based on a steric-hindrance-mediated on- rate, which may allow the tapered tip structures that are typical at growing microtubule plus ends to assist in facilitating the rapid arrival of EB1 to the microtubule plus-end.