Browsing by Subject "nuclear magnetic resonance"
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Item Determining the Intrinsic Properties of the C1B Domain that Influence PKC Ligand Specificity and Sensitivity to Reactive Oxygen Species(2013-06-04) Stewart, Mikaela D.Each member of the protein kinase C (PKC) family activates cell signaling pathways with different and sometimes opposing cell functions, such as cell division, migration, or death. Because of the importance of these processes in human diseases and disorders like cancer, stroke, and Alzheimer?s disease, there is a need for drugs which modify the action of PKC. However, drug design is difficult due to the complicated nature of PKC regulation. To better understand the differential regulation of PKC activity, these studies probe the structure, dynamics, and reactivity of one of the domains responsible for PKC regulation, C1B. C1B binds signaling molecules and translocates PKC to membranes in order to release the kinase domain from inhibition. Mutagenesis and ligand-binding assays monitored with fluorescence and nuclear magnetic resonance (NMR) techniques show that a single variable residue in C1B dramatically affects the sensitivity to signal activators. Investigation of the domain structure and dynamics using NMR revealed the identity of this residue alters the dynamics of the activator binding loops, without changing the structure. NMR studies of the C1B variants in membrane-mimicking micelles showed this residue also changes the interaction of the regulatory domain with lipids. These results demonstrate PKC isoforms have evolved specific functions by tuning dynamics and membrane affinity. Alternatively, PKC can be activated by reactive oxygen species by a mechanism that does not require binding of signaling molecules or membrane localization. To investigate the role of C1B in this type of signaling, the regulatory domain reactivity is monitored via NMR and gel electrophoresis. These studies reveal a particular cysteine residue in C1B that is most reactive, an alternative conformation of C1B in which this residue is more exposed, and modification of C1B leads to unfolding and zinc loss. Because the regulatory domains are responsible for auto-inhibition of the kinase domain, C1B unfolding provides a plausible explanation for activation of PKC by reactive oxygen species. The relation of the intrinsic C1B properties to the activation of PKC can be used to develop drugs with a single mechanism and to better understand how closely related signaling proteins develop specific functions.Item Investigation of Cryo-Cooled Microcoils for MRI(2012-10-19) Godley, Richard FranklinWhen increasing magnetic resonance imaging (MRI) resolution into the micron scale, image signal-to-noise ratio (SNR) can be maintained by using small radiofrequency (RF) coils in close proximity to the sample being imaged. Micro-scale RF coils (microcoils) can be easily fabricated on chip and placed adjacent to a sample under test. However, the high series resistance of microcoils limits the SNR due to the thermal noise generated in the copper. Cryo-cooling is a potential technique to reduce thermal noise in microcoils, thereby recovering SNR. In this research, copper microcoils of two different geometries have been cryo-cooled using liquid nitrogen. Quality-factor (Q) measurements have been taken to quantify the reduction in resistance due to cryo-cooling. Image SNR has been compared between identical coils at room temperature and liquid nitrogen temperature. The relationship between the drop in series resistance and the increase in image SNR has been analyzed, and these measurements compared to theory. While cryo-cooling can bring about dramatic increases in SNR, the extremely low temperature of liquid nitrogen is incompatible with living tissue. In general, the useful imaging region of a coil is approximately as deep as the coil diameter, thus cryo-cooling of coils has been limited in the past to larger coils, such that the thickness of a conventional cryostat does not put the sample outside of the optimal imaging region. This research utilizes a scheme of microfluidic cooling (developed in the Texas A&M NanoBio Systems Lab), which greatly reduces the volume of liquid nitrogen required to cryo-cool the coil. Along with a small gas phase nitrogen gap, this eliminates the need for a bulky cryostat. This thesis includes a review of the existing literature on cryo-cooled coils for MRI, as well as a review of planar pair coils and spiral microcoils in MR applications. Our methods of fabricating and testing these coils are described, and the results explained and analyzed. An image SNR improvement factor of 1.47 was achieved after cryo-cooling of a single planar pair coil, and an improvement factor of 4 was achieved with spiral microcoils.Item Modeling, analysis and control of quantum electronic devices(2009-06-02) Zhang, ZhigangThis dissertation focuses on two connected areas: quantum computation and quantum control. Two proposals to construct a quantum computer, using nuclear magnetic resonance (NMR) and superconductivity, are introduced. We give details about the modeling, qubit realization, one and two qubit gates and measurement in the language that mathematicians can understand and fill gaps in the original literatures. Two experimental examples using liquid NMR are also presented. Then we proceed to investigate an example of quantum control, that of a magnetometer using quantum feedback. Previous research has shown that feedback makes the measurement robust to an unknown parameter, the number of atoms involved, with the assumption that the feedback is noise free. To evaluate the effect of the feedback noise, we extend the original model by an input noise term. We then compute the steady state performance of the Kalman filter for both the closed-loop and open-loop cases and retrieve the estimation error variances. The results are compared and criteria for evaluating the effects of input noise are obtained. Computations and simulations show that the level of input noise affects the measurement by changing the region where closed loop feedback is beneficial.