Matching Items (610)
Interactions driving the collapse of islet amyloid polypeptide: implications for amyloid aggregation
Description
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-residue intrinsically disordered hormone involved in glucose regulation and gastric emptying. The aggregation of hIAPP into amyloid fibrils is believed to play a causal role in type 2 diabetes. To date, not much is known about the monomeric state of hIAPP or how it undergoes an irreversible transformation from disordered peptide to insoluble aggregate. IAPP contains a highly conserved disulfide bond that restricts hIAPP(1-8) into a short ring-like structure: N_loop. Removal or chemical reduction of N_loop not only prevents cell response upon binding to the CGRP receptor, but also alters the mass per length distribution of hIAPP fibers and the kinetics of fibril formation. The mechanism by which N_loop affects hIAPP aggregation is not yet understood, but is important for rationalizing kinetics and developing potential inhibitors. By measuring end-to-end contact formation rates, Vaiana et al. showed that N_loop induces collapsed states in IAPP monomers, implying attractive interactions between N_loop and other regions of the disordered polypeptide chain . We show that in addition to being involved in intra-protein interactions, the N_loop is involved in inter-protein interactions, which lead to the formation of extremely long and stable β-turn fibers. These non-amyloid fibers are present in the 10 μM concentration range, under the same solution conditions in which hIAPP forms amyloid fibers. We discuss the effect of peptide cyclization on both intra- and inter-protein interactions, and its possible implications for aggregation. Our findings indicate a potential role of N_loop-N_loop interactions in hIAPP aggregation, which has not previously been explored. Though our findings suggest that N_loop plays an important role in the pathway of amyloid formation, other naturally occurring IAPP variants that contain this structural feature are incapable of forming amyloids. For example, hIAPP readily forms amyloid fibrils in vitro, whereas the rat variant (rIAPP), differing by six amino acids, does not. In addition to being highly soluble, rIAPP is an effective inhibitor of hIAPP fibril formation . Both of these properties have been attributed to rIAPP's three proline residues: A25P, S28P and S29P. Single proline mutants of hIAPP have also been shown to kinetically inhibit hIAPP fibril formation. Because of their intrinsic dihedral angle preferences, prolines are expected to affect conformational ensembles of intrinsically disordered proteins. The specific effect of proline substitutions on IAPP structure and dynamics has not yet been explored, as the detection of such properties is experimentally challenging due to the low molecular weight, fast reconfiguration times, and very low solubility of IAPP peptides. High-resolution techniques able to measure tertiary contact formations are needed to address this issue. We employ a nanosecond laser spectroscopy technique to measure end-to-end contact formation rates in IAPP mutants. We explore the proline substitutions in IAPP and quantify their effects in terms of intrinsic chain stiffness. We find that the three proline mutations found in rIAPP increase chain stiffness. Interestingly, we also find that residue R18 plays an important role in rIAPP's unique chain stiffness and, together with the proline residues, is a determinant for its non-amyloidogenic properties. We discuss the implications of our findings on the role of prolines in IDPs.
ContributorsCope, Stephanie M (Author) / Vaiana, Sara M (Thesis advisor) / Ghirlanda, Giovanna (Committee member) / Ros, Robert (Committee member) / Lindsay, Stuart M (Committee member) / Ozkan, Sefika B (Committee member) / Arizona State University (Publisher)
Created2013
Description
This thesis describes the fabrication of several new classes of Ge1-x-ySixSny materials with the required compositions and crystal quality to engineer the band gaps above and below that of elemental Ge (0.8 eV) in the near IR. The work initially focused on Ge1-x-ySixSny (1-5% Sn, 4-20% Si) materials grown on Ge(100) via gas-source epitaxy of Ge4H10, Si4H10 and SnD4. Both intrinsic and doped layers were produced with defect-free microstructure and viable thickness, allowing the fabrication of high-performance photodetectors. These exhibited low ideality factors, state-of-the-art dark current densities and adjustable absorption edges between 0.87 and 1.03 eV, indicating that the band gaps span a significant range above that of Ge. Next Sn-rich Ge1-x-ySixSny alloys (2-4% Si and 4-10% Sn) were fabricated directly on Si and were found to show significant optical emission using photoluminescence measurements, indicating that the alloys have direct band gaps below that of pure Ge in the range of 0.7-0.55 eV. A series of Sn-rich Ge1-x-ySixSny analogues (y>x) with fixed 3-4% Si content and progressively increasing Sn content in the 4-10% range were then grown on Ge buffered Si platforms for the purpose of improving the material's crystal quality. The films in this case exhibited lower defect densities than those grown on Si, allowing a meaningful study of both the direct and indirect gaps. The results show that the separation of the direct and indirect edges can be made smaller than in Ge even for non-negligible 3-4% Si content, confirming that with a suitable choice of Sn compositions the ternary Ge1-x-ySixSny reproduces all features of the electronic structure of binary Ge1-ySny, including the sought-after indirect-to-direct gap cross over. The above synthesis of optical quality Ge1-x-ySixSny on virtual Ge was made possible by the development of high quality Ge-on-Si buffers via chemical vapor deposition of Ge4H10. The resultant films exhibited structural and electrical properties significantly improved relative to state-of-the-art results obtained using conventional approaches. It was found that pure Ge4H10 facilitates the control of residual doping and enables p-i-n devices whose dark currents are not entirely determined by defects and whose zero-bias collection efficiencies are higher than those obtained from samples fabricated using alternative Ge-on-Si approaches.
ContributorsXu, Chi (Author) / Kouvetakis, John (Thesis advisor) / Menéndez, Jose (Thesis advisor) / Chizmeshya, Andrew (Committee member) / Drucker, Jeffrey (Committee member) / Ponce, Fernando (Committee member) / Arizona State University (Publisher)
Created2013
Description
ABSTRACT This thesis focuses on structural characterizations and optical properties of Si, Ge based semiconductor alloys. Two material systems are characterized: Si-based III-V/IV alloys, which represent a possible pathway to augment the optical performance of elemental silicon as a solar cell absorber layer, and Ge-based Ge1-ySny and Ge1-x-ySixSny systems which are applicable to long wavelength optoelectronics. Electron microscopy is the primary tool used to study structural properties. Electron Energy Loss spectroscopy (EELS), Ellipsometry, Photoluminescence and Raman Spectroscopy are combined to investigate electronic band structures and bonding properties. The experiments are closely coupled with structural and property modeling and theory. A series of III-V-IV alloys have been synthesized by the reaction of M(SiH3)3 (M = P, As) with Al atoms from a Knudsen cell. In the AlPSi3 system, bonding configurations and elemental distributions are characterized by scanning transmission electron microscopy (STEM)/EELS and correlated with bulk optical behavior. The incorporation of N was achieved by addition of N(SiH3)3 into the reaction mixture yielding [Al(As1-xNx)]ySi5-2yalloys. A critical point analysis of spectroscopic ellipsometry data reveals the existence of direct optical transitions at energies as low as 2.5 eV, well below the lowest direct absorption edge of Si at 3.3 eV. The compositional dependence of the lowest direct gap and indirect gap in Ge1-ySny alloys extracted from room temperature photoluminescence indicates a crossover concentration of yc =0.073, much lower than virtual crystal approximation but agrees well with large atomic supercells predictions. A series of Ge-rich Ge1-x-ySixSny samples with a fixed 3-4% Si content and progressively increasing Sn content in the 4-10% range are grown and characterized by electron microscopy and photoluminescence. The ternary represents an attractive alternative to Ge1-ySny for applications in IR optoelectronic technologies.
ContributorsJiang, Liying (Author) / Menéndez, Jose (Thesis advisor) / Kouvetakis, John (Thesis advisor) / Smith, David J. (Committee member) / Chizmeshya, Andrew V.G (Committee member) / Chamberlin, Ralph (Committee member) / Arizona State University (Publisher)
Created2014
Description
During the downswing all golfers must roll their forearms and twist the club handle in order to square the club face into impact. Anecdotally some instructors say that rapidly twisting the handle and quickly closing the club face is the best technique while others disagree and suggest the opposite. World class golfers have swings with a range of club handle twist velocities (HTV) from very slow to very fast and either method appears to create a successful swing. The purpose of this research was to discover the relationship between HTV at impact and selected body and club biomechanical characteristics during a driver swing. Three-dimensional motion analysis methods were used to capture the swings of 94 tour professionals. Pearson product-moment correlation was used to determine if a correlation existed between HTV and selected biomechanical characteristics. The total group was also divided into two sub-groups of 32, one group with the fastest HTV (Hi-HTV) and the other with the slowest HTV (Lo-HTV). Single factor ANOVAs were completed for HTV and each selected biomechanical parameter. No significant differences were found between the Hi-HTV and Lo-HTV groups for both clubhead speed and driving accuracy. Lead forearm supination velocity at impact was found to be significantly different between groups with the Hi-HTV group having a higher velocity. Lead wrist extension velocity at impact, while not being significantly different between groups was found to be positive in both groups, meaning that the lead wrist is extending at impact. Lead wrist ulnar deviation, lead wrist release and trail elbow extension velocities at maximum were not significantly different between groups. Pelvis rotation, thorax rotation, pelvis side bend and pelvis rotation at impact were all significantly different between groups, with the Lo-HTV group being more side bent tor the trail side and more open at impact. These results suggest that world class golfers can successfully use either the low or high HTV technique for a successful swing. From an instructional perspective it is important to be aware of the body posture and wrist/forearm motion differences between the two techniques so as to be consistent when teaching either method.
ContributorsCheetham, Phillip (Author) / Hinrichs, Richard (Thesis advisor) / Ringenbach, Shannon (Committee member) / Dounskaia, Natalia (Committee member) / Crews, Debra (Committee member) / Arizona State University (Publisher)
Created2014
Description
Multiple quantum well (MQW) structures have been employed in a variety of solid state devices. The InGaAs/GaAs material system is of special interest for many optoelectronic applications. This study examines epitaxial growth and defect creation in InGaAs/GaAs MQWs at its initial stage. Correlations between physical properties, crystal perfection of epitaxial structures, and growth conditions under which desired properties are achieved appear as highly important for the realization and final performance of semiconductor based devices.
Molecular beam epitaxy was utilized to grow InGaAs/GaAs MQW structures with a variation in deposition temperature Tdep among the samples to change crystalline and physical properties. High resolution x-ray diffraction and transmission electron microscopy were utilized to probe crystal properties, whereas photoluminescence spectroscopy evaluated optical response. An optimal growth temperature Tdep=505°C was found for 20% In composition. The density of 60° primary and secondary dislocation loops increased continuously at lower growth temperatures and reduced crystal perfection, as evaluated by lateral and vertical coherence lengths and diffuse scattering in reciprocal space maps. Likewise, the strength of non-radiative Shockley-Read-Hall recombination increased as deposition temperature was reduced. Elevated deposition temperature led to InGaAs decay in the structures and manifested in different crystalline defects with a rather isotropic distribution and no lateral ordering. High available thermal energy increased atomic surface diffusivity and resulted in growth surface instability against perturbations, manifesting in lateral layer thickness undulations. Carriers in structures grown at elevated temperature experience localization in local energy minima.InGaAs/GaAs MQW structures reveal correlation between their crystal quality and optical properties. It can be suggested that there is an optimal growth temperature range for each In composition with high crystal perfection and best physical response.
Molecular beam epitaxy was utilized to grow InGaAs/GaAs MQW structures with a variation in deposition temperature Tdep among the samples to change crystalline and physical properties. High resolution x-ray diffraction and transmission electron microscopy were utilized to probe crystal properties, whereas photoluminescence spectroscopy evaluated optical response. An optimal growth temperature Tdep=505°C was found for 20% In composition. The density of 60° primary and secondary dislocation loops increased continuously at lower growth temperatures and reduced crystal perfection, as evaluated by lateral and vertical coherence lengths and diffuse scattering in reciprocal space maps. Likewise, the strength of non-radiative Shockley-Read-Hall recombination increased as deposition temperature was reduced. Elevated deposition temperature led to InGaAs decay in the structures and manifested in different crystalline defects with a rather isotropic distribution and no lateral ordering. High available thermal energy increased atomic surface diffusivity and resulted in growth surface instability against perturbations, manifesting in lateral layer thickness undulations. Carriers in structures grown at elevated temperature experience localization in local energy minima.InGaAs/GaAs MQW structures reveal correlation between their crystal quality and optical properties. It can be suggested that there is an optimal growth temperature range for each In composition with high crystal perfection and best physical response.
ContributorsKarow, Matthias (Author) / Honsberg, C. (Christiana B.) (Thesis advisor) / Faleev, Nikolai N (Committee member) / Ning, Cun-Zheng (Committee member) / Arizona State University (Publisher)
Created2014
Description
This dissertation describes Space Vector 1 and Space Vector 2, two video games that introduce Newtonian mechanics concepts. Space Vector 1 is a side-scrolling game, in which players choose to drop bombs or supplies. Players had to identify if the physics was correct during a mission, or they had to plot the trajectory of a falling object, which was then simulated. In Space Vector 2, players were given velocity and acceleration values and had to plot the trajectory of a spaceship across a grid, or players were given a trajectory of a spaceship on a grid and had to program the velocity and acceleration values to produce the trajectory. Space Vector 1 was evaluated with 65 college undergraduates. Space Vector 2 was evaluated with 18 high school students. All participants were given a subset of the Force Concept Inventory, a standard assessment tool in physics education, as a pretest and posttest. Space Vector 1 was evaluated with a single group pretest-posttest design. Space Vector 2 was evaluated with a 2 x 2 ANOVA, where the factors were game mechanic (prediction mechanic or programming mechanic) and bonus questions (bonus question after a mission or no bonus question). Bayesian statistical methods were used for the data analysis. The best estimate for the average change in test scores for Space Vector 1 was a score gain of 1.042 (95% Highest Density Interval (HDI) [0.613, 1.487]) with an effect size of 0.611 (95% HDI [0.327, 0.937]). The best estimate for the grand mean of change scores in Space Vector 2 was an increase of 0.78 (95% HDI [-0.3, 1.85]) with an effect size of 0.379 (95% HDI [-0.112, 0.905]). The prediction
o bonus question version produced the largest change in score, where the best estimate for the mean change score was an increase of 1.2. The estimation intervals for the Space Vector 2 results were wide, and all included zero as a credible value.
o bonus question version produced the largest change in score, where the best estimate for the mean change score was an increase of 1.2. The estimation intervals for the Space Vector 2 results were wide, and all included zero as a credible value.
ContributorsKeylor, Eric Karl (Author) / Gee, James P. (Thesis advisor) / Stevens, Scott M. (Committee member) / Nelson, Brian C. (Committee member) / Atkinson, Robert K. (Committee member) / Arizona State University (Publisher)
Created2014
Description
Single molecule identification is one essential application area of nanotechnology. The application areas including DNA sequencing, peptide sequencing, early disease detection and other industrial applications such as quantitative and quantitative analysis of impurities, etc. The recognition tunneling technique we have developed shows that after functionalization of the probe and substrate of a conventional Scanning Tunneling Microscope with recognition molecules ("tethered molecule-pair" configuration), analyte molecules trapped in the gap that is formed by probe and substrate will bond with the reagent molecules. The stochastic bond formation/breakage fluctuations give insight into the nature of the intermolecular bonding at a single molecule-pair level. The distinct time domain and frequency domain features of tunneling signals were extracted from raw signals of analytes such as amino acids and their enantiomers. The Support Vector Machine (a machine-learning method) was used to do classification and predication based on the signal features generated by analytes, giving over 90% accuracy of separation of up to seven analytes. This opens up a new interface between chemistry and electronics with immediate implications for rapid Peptide/DNA sequencing and molecule identification at single molecule level.
ContributorsZhao, Yanan, 1986- (Author) / Lindsay, Stuart (Thesis advisor) / Nemanich, Robert (Committee member) / Qing, Quan (Committee member) / Ros, Robert (Committee member) / Zhang, Peiming (Committee member) / Arizona State University (Publisher)
Created2014
ContributorsHoeckley, Stephanie (Performer) / Lee, Juhyun (Performer) / ASU Library. Music Library (Publisher)
Created2018-03-24
Description
This thesis explores the different aspects of higher curvature gravity. The "membrane paradigm" of black holes in Einstein gravity is extended to black holes in f(R) gravity and it is shown that the higher curvature effects of f(R) gravity causes the membrane fluid to become non-Newtonian. Next a modification of the null energy condition in gravity is provided. The purpose of the null energy condition is to filter out ill-behaved theories containing ghosts. Conformal transformations, which are simple redefinitions of the spacetime, introduces serious violations of the null energy condition. This violation is shown to be spurious and a prescription for obtaining a modified null energy condition, based on the universality of the second law of thermodynamics, is provided. The thermodynamic properties of the black holes are further explored using merger of extremal black holes whose horizon entropy has topological contributions coming from the higher curvature Gauss-Bonnet term. The analysis refutes the prevalent belief in the literature that the second law of black hole thermodynamics is violated in the presence of the Gauss-Bonnet term in four dimensions. Subsequently a specific class of higher derivative scalar field theories called the galileons are obtained from a Kaluza-Klein reduction of Gauss-Bonnet gravity. Galileons are null energy condition violating theories which lead to violations of the second law of thermodynamics of black holes. These higher derivative scalar field theories which are non-minimally coupled to gravity required the development of a generalized method for obtaining the equations of motion. Utilizing this generalized method, it is shown that the inclusion of the Gauss-Bonnet term made the theory of gravity to become higher derivative, which makes it difficult to make any statements about the connection between the violation of the second law of thermodynamics and the galileon fields.
ContributorsChatterjee, Saugata (Author) / Parikh, Maulik K (Thesis advisor) / Easson, Damien (Committee member) / Davies, Paul (Committee member) / Arizona State University (Publisher)
Created2014
Description
Inductors are fundamental components that do not scale well. Their physical limitations to scalability along with their inherent losses make them the main obstacle in achieving monolithic system-on-chip platform (SoCP). For past decades researchers focused on integrating magnetic materials into on-chip inductors in the quest of achieving high inductance density and quality factor (QF). The state of the art on-chip inductor is made of an enclosed magnetic thin-film around the current carrying wire for maximum flux amplification. Though the integration of magnetic materials results in enhanced inductor characteristics, this approach has its own challenges and limitations especially in power applications. The current-induced magnetic field (HDC) drives the magnetic film into its saturation state. At saturation, inductance and QF drop to that of air-core inductors, eliminating the benefits of integrating magnetic materials. Increasing the current carrying capability without substantially sacrificing benefits brought on by the magnetic material is an open challenge in power applications. Researchers continue to address this challenge along with the continuous improvement in inductance and QF for RF and power applications.
In this work on-chip inductors incorporating magnetic Co-4%Zr-4%Ta -8%B thin films were fabricated and their characteristics were examined under the influence of an externally applied DC magnetic field. It is well established that spins in magnetic materials tend to align themselves in the same direction as the applied field. The resistance of the inductor resulting from the ferromagnetic film can be changed by manipulating the orientation of magnetization. A reduction in resistance should lead to decreases in losses and an enhancement in the QF. The effect of externally applied DC magnetic field along the easy and hard axes was thoroughly investigated. Depending on the strength and orientation of the externally applied field significant improvements in QF response were gained at the expense of a relative reduction in inductance. Characteristics of magnetic-based inductors degrade with current-induced stress. It was found that applying an externally low DC magnetic field across the on-chip inductor prevents the degradation in inductance and QF responses. Examining the effect of DC magnetic field on current carrying capability under low temperature is suggested.
In this work on-chip inductors incorporating magnetic Co-4%Zr-4%Ta -8%B thin films were fabricated and their characteristics were examined under the influence of an externally applied DC magnetic field. It is well established that spins in magnetic materials tend to align themselves in the same direction as the applied field. The resistance of the inductor resulting from the ferromagnetic film can be changed by manipulating the orientation of magnetization. A reduction in resistance should lead to decreases in losses and an enhancement in the QF. The effect of externally applied DC magnetic field along the easy and hard axes was thoroughly investigated. Depending on the strength and orientation of the externally applied field significant improvements in QF response were gained at the expense of a relative reduction in inductance. Characteristics of magnetic-based inductors degrade with current-induced stress. It was found that applying an externally low DC magnetic field across the on-chip inductor prevents the degradation in inductance and QF responses. Examining the effect of DC magnetic field on current carrying capability under low temperature is suggested.
ContributorsKhdour, Mahmoud (Author) / Yu, Hongbin (Thesis advisor) / Pan, George (Committee member) / Goryll, Michael (Committee member) / Bearat, Hamdallah (Committee member) / Arizona State University (Publisher)
Created2014