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Application of Dissolution Dynamic Nuclear Polarization to the Characterization of Reactions Involving Large MoleculesLee, Youngbok 03 October 2013 (has links)
Nuclear magnetic resonance (NMR) spectroscopy is one of the most important analytical tools for organic and biological chemistry. It provides not only detailed information on the structure of small molecules and macromolecules, but also on molecular interactions. Because of the inherent low sensitivity of NMR, a long signal averaging time or a high spin concentration is often required. A variety of methods have been explored to improve the sensitivity of NMR. Especially, large signal gains can be obtained by hyperpolarization of the nuclear spins. NMR signals of hyperpolarized samples are enhanced by several orders of magnitude. Dissolution Dynamic Nuclear Polarization (D-DNP) is a versatile technique capable of polarizing many different nuclei in the solid state, and subsequently providing a hyperpolarized liquid sample following a dissolution step. The resulting signal enhancement has made it possible to obtain detailed information in research fields as varied as metabolic imaging or enzyme catalysis. This dissertation aims to extend the applicability of D-DNP into new areas of chemistry, which involve the characterization of interactions and reactions involving large molecules.
In a first project, fluorine hyperpolarization is exploited to investigate protein-ligand interactions. The enhancement of 19F signal allows for the detection of submicromolar concentrations of fluorinated ligands in the strong-, intermediate-, and weak-binding regimes. Several NMR parameters are utilized to observe ligand binding to the macromolecule, and to determine dissociation constants.
In a second project, competitive binding of ligands to the same binding pocket on a protein is investigated. Here, polarization flows from a first ligand hyperpolarized on protons to the protein, and then to the second ligand. The buildup in function of time of the signals due to this relayed nuclear Overhauser effect contains structural information on the binding epitope.
In a third project, the aim is to directly detect a larger molecule, a polymer, which has been synthesized starting from hyperpolarized monomers. Using DNP, single scan observation of 13C, a common nucleus with large chemical shift dispersion, is possible. Time resolved 13C NMR spectroscopy in combination with kinetic models permits the description of polymerization reaction of the living anionic polymerization of styrene. In summary, several approaches have been investigated for utilizing a large hyperpolarization initially produced on small molecules, for the benefit of characterizing properties of macromolecules. These developments extend the capabilities of D-DNP and demonstrate the potential for leading to new applications in fields as diverse as drug discovery and polymer science.
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Using Technology-Based Rapid Cycle Quality Improvement in Preceptorships to Support Curricular Change in BSN-to-DNP ProgramsHall, Katherine C., Diffenderfer, Sandy, Stidham, April, Mullins, Christine M. 01 April 2017 (has links)
No description available.
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Strategic Innovation Between PhD and DNP Programs: Collaboration, Collegiality, and Shared ResourcesEdwards, Joellen, Rayman, Kathleen, Diffenderfer, Sandra, Stidham, April 01 July 2016 (has links)
Background At least 111 schools and colleges of nursing across the nation provide both PhD and DNP programs (AACN, 2014a). Collaboration between nurses with doctoral preparation as researchers (PhD) and practitioners (DNP) has been recommended as essential to further the profession; that collaboration can begin during the educational process. Purpose The purpose of this paper is to describe the development and implementation of successful DNP and PhD program collaboration, and to share the results of that collaboration in an educational setting. Methods Faculty set strategic goals to maximize the effectiveness and efficiency of both new DNP and existing PhD programs. The goals were to promote collaboration and complementarity between the programs through careful capstone and dissertation differentiation, complementary residency activities, joint courses and inter-professional experiences; promote collegiality in a blended on-line learning environment through shared orientation and intensive on-campus sessions; and maximize resources in program delivery through a supportive organizational structure, equal access to technology support, and shared faculty responsibilities as appropriate to terminal degrees. Discussion Successes such as student and faculty accomplishments, and challenges such as managing class size and workload, are described. Conclusions Collaboration, collegiality and the sharing of resources have strengthened and enriched both programs and contributed to the success of students, faculty. These innovative program strategies can provide a solid foundation for DNP and PhD collaboration.
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Achieving the Triple Aim in Healthcare through the Preparation of DNPs as Experts in EBPOusley, Lisa, Pope, Victoria, Gentry, Retha D. 27 August 2018 (has links)
No description available.
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Sensitivity Enhanced NMRLottmann, Philip 28 January 2014 (has links)
Das Thema dieser Arbeit ist die Sensitivitätserhöhung der Kernspinmagnetresonanzspektroskopie (NMR-Spektroskopie) für die Anwendung an biologischen Systemen durch dynamische Kernspinpolarisation (DNP). Dementsprechend wurden die experimentellen Bedingungen möglichst ähnlich zu einer physiologischen Umgebung in Lösung gewählt. Unter diesen Voraussetzungen ist der Overhauser-Effekt der zentrale Mechanismus für DNP. Dieser ist von der relativen Diffusion zwischen den Kernspins des Zielmoleküls und dem polarisierenden Molekül, welchesein ungepaartes Elektron aufweist, abhängig. Als experimenteller Ansatz für diese Arbeit wurde ein Shuttle-DNP-Spektrometer mit Proben im flüssigen Zustand ausgewählt. Hierbei wurden die Kernspins bei einem Magnetfeld von 0,34 T polarisiert und für eine hoch auflösende NMR-Detektion in ein Magnetfeld von 14,09 T transferiert. Mehrere technische Anpassungen, welche zu einer Erhöhung der Stabilität und Reproduzierbarkeit der Messungen führten, wurden sukzessiv implementiert. Für die Signale der Protonen von L-Tryptophan wurde im Hochfeld eine DNP-Verstärkung εhf von bis zu -2,4 (H<sup>η2</sup>) gemessen. Darauf aufbauend wurde ein allgemeiner Verstärkungsfaktor εglobal eingeführt. Dieser beinhaltete sowohl die Vorteile des Shuttle-DNP-Spektrometers, wie beispielsweise die schnellere Aufnahmerate der DNP-Experimente als auch die Nachteile, wie etwa die Linienverbreiterung der Signale durch die Gegenwart des polarisierenden Radikals. Anschließend wurde dieser Faktor schrittweise auf eindimensionale Messungen angewandt und an diese
angepasst. Hierfür wurden die Aufbaurate der Polarisation und die Aufnahmezeit der Messungen mit DNP und Boltzmann-Polarisation optimiert, um das maximale Signal-zu-Rauschen-Verhältnis pro Messzeit zu erhalten. Diese Parameter basieren auf T1 bzw. T2∗. Das Ergebnis dieser Schritte war ein angewandter, allgemeiner Verstärkungsfaktor εapp von -4.0 für Hδ1 von L-Tryptophan. Des Weiteren wurden die Kernspineigenschaften von Protonen für DNP, wie z.B.die Relaxationsraten, gemessen und miteinander verglichen. Der daraus abgeleitete Kopplungsfaktor implizierte, dass die intermolekulare, dipolare Wechselwirkung zwischen den Kernspins des Zielmoleküls und dem Elektron des polarisierenden Radikals von der räumlichen Zugänglichkeit der Kernspins beeinflusst wurde. Zudem wurde gezeigt, dass diese Wechselwirkung am besten durch ein Model basierend auf translatorischer Diffusion beschrieben werden konnte. Mit diesem wurde der Abstand der dichtesten Annährung zwischen den Kernspins und dem ungepaartem Elektron bestimmt. Diese Abstände reichen entsprechend der Zugänglichkeit des jeweiligen Protons von 3 bis 5 Å. Darauf aufbauend wurden die DNP-Verstärkungen für Kohlenstoff gemessen. Für deuteriertes L-Tryptophan-d8,15N2,13C11 wurden Verstärkungen zwischen -0,3 und -2,5 erzielt. Durch weitere Berechnungen wurde gezeigt, dass diese Verstärkungen mit den zuvor berechneten Abständen der dichtesten Annäherung der Protonen übereinstimmten und dadurch den Ansatz des Models der translatorischen Diffusion untermauerten. In weiteren Messungen an protoniertem L-Tryptophan-15N2,13C11 wurde der Drei-Spin-Effekt erstmalig bei einem gelösten Molekül beobachtet. Dieser Effekt basierte auf der dipolaren Wechselwirkung zwischen den Spins der Protonen, Kohlenstoffkerne und Radikal-Elektronen. Er verursachte positive Signalverstärkungen von bis zu 2,3 für alle Kohlenstoffe außer dem Carbonyl-Kohlenstoff, welcher eine Signalverstärkung von -2,5 aufwies. Diese Ergebnisse waren in Übereinstimmung mit einem erweiterten Kopplungsfaktor, der die intramolekulare Wechselwirkung zwischen Kohlenstoff und Proton neben der zwischen Kohlenstoff und Elektron berücksichtigte. In einem abschließenden Schritt wurden DNP-Experimente an einem Protein (Ubiquitin-U-15N,U-13C) durchgeführt. Zu diesem Zweck wurden zweidimensionale Shuttle-DNP-1H-13C-HSQC-Spektren aufgenommen. Zum ersten Mal konnte ein DNP-Transfer zu der Oberfläche eines Proteins in Lösung nachgewiesen werden.
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Doctor of Nursing Practice Roles in AcademiaRaisor, Jodi Renee 01 January 2019 (has links)
Over 15,000 master’s and doctoral degree students in the United States were denied admission to nursing schools in 2014 because of insufficient nursing faculty. In 2016, over 64,000 undergraduate and graduate students were unable to gain admission to nursing school due to the effects of faculty shortages. This project explored the role of the Doctor of Nursing Practice (DNP)-prepared nurse in academic settings using a systematic review of the literature to determine the role of DNP-prepared nurses in academia. Souza’s systematic review model and Melnyk’s levels of evidence were used to guide the search, review, and the selection of scholarly articles published between 2005 to 2019. A chart of preferred reporting items for systematic reviews and meta-analyses chart was used to organize and select 14 articles meeting the review criteria and included in the analysis. Four themes emerged from the analysis of literature: role in academia from the dean’s and director’s perspective, DNP role as a teacher, preparation for faculty role, and leaving the faculty role. Confusion over the role of the DNP in academia was also identified as a factor affecting DNPs in academic practice settings; however, DNPprepared nurses have the clinical experience, knowledge, and skills to provide evidence-based teaching and fill the gap in practice needed in academic settings. This project may promote positive social change by raising awareness of the role of the DNP in academia to reduce the faculty shortage.
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Preparing Faculty to Lead Doctor of Nursing Practice Projects: A Faculty Development Pilot ProjectLazear, Janice, Hemphill, Jean Croce 01 November 2020 (has links)
Faculty expressed a need to improve knowledge and skills related to leading Doctor of Nursing Practice projects. A mentoring program was designed to provide faculty the skills to increase confidence when leading Doctor of Nursing Practice projects. The program included an assessment of confidence of six key skills. The intervention included didactic and individual experiential learning that coincided with student progression through project courses. Participants' self-identified areas of need included understanding application of translation science, methods, statistical choices, and all phases of analysis. Four of the six elements were improved from baseline, with two statistically significant, Project Analysis (M = 2.05, SD =0.88, p < .041) and Project Dissemination (M = 2.25, SD = 0.89, p < .046). The pilot project was a first step in assessing strategies for educating and mentoring faculty leading Doctor of Nursing Practice projects.
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Preparing Faculty To Lead Doctor of Nursing Practice Projects: A Faculty Development Pilot Project.Lazear, Janice, Hemphill, Jean C. 20 January 2021 (has links) (PDF)
Background/Introduction: A mentoring program was designed to provide faculty the skills to increase confidence when leading Doctor of Nursing Practice projects. The program included an assessment of confidence of six key skills. The intervention included didactic and individual experiential learning that coincided with student progression through project courses.Purpose: The purpose of this project was to provide an intervention to promote faculty confidence when leading DNP projects. The objectives were to: assess faculty participants' self-perceived confidence regarding needed leading DNP projects, create and implement a faculty development program based on the responses, and evaluate the faculty perception of confidence post-intervention.
Methods OR Process/Procedures: Participants completed a questionnaire to evaluate perception of confidence regarding leading student DNP projects. The intervention included didactic and individual mentoring, synchronous educational and guidance sessions, along with individual mentoring sessions. The sessions were provided at intervals over 10 months. Mentoring corresponded to DNP course progression. Key skills included project identification, evidence evaluation, frameworks, evidence critiques, methods, implementation, data analysis, and dissemination. Three to four months after the mentoring ended, participants were asked to rate their confidence on the same questionnaire.Results: Participants' self-identified areas of need included understanding application of translation science, methods, statistical choices, and all phases of analysis. Four of the six elements were improved from baseline, with two statistically significant, Project Analysis and Project Dissemination.Limitations: Limitations included, small sample size, questionnaire only tested for face validity, and drop-out rate over time.Conclusions: Mentoring while actively working with student projects is vital to apply concepts in real-time. Pairing junior faculty with senior faculty enhances experiential learning needed to effectively lead DNP projects. Sharing real-time feedback for each component of students' proposals and manuscripts allowed participants to observe mentors providing student guidance.
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Quantitative Determination of Chemical Processes by Dynamic Nuclear Polarization Enhanced Nuclear Magnetic Resonance SpectroscopyZeng, Haifeng 2012 May 1900 (has links)
Dissolution dynamic nuclear polarization (DNP) provides several orders of magnitude of NMR signal enhancement by converting the much larger electron spin polarization to nuclear spin polarization. Polarization occurs at low temperature (1.4K) and is followed by quickly dissolving the sample for room temperature NMR detection. DNP is generally applicable to almost any small molecules and can polarize various nuclei including 1H, 19F and 13C. The large signal from DNP enhancement reduces the limit of detection to micromolar or sub-micromolar concentration in a single scan. Since DNP enhancement often provides the only source for the observable signal, it enables tracking of the polarization flow. Therefore, DNP is ideal for studying chemical processes. Here, quantitative tools are developed to separate kinetics and spin relaxation, as well as to obtain structural information from these measurements. Techniques needed for analyzing DNP polarized sample are different from those used in conventional NMR because a large, yet non-renewable hyperpolarization is available. Using small flip angle pulse excitation, the hyperpolarization can still be divided into multiple scans. Based on this principle, a scheme is presented that allows reconstruction of indirect spectral dimensions similarly to conventional 2D NMR. Additionally, small flip angle pulses can be used to obtain a succession of scans separated in time. A model describing the combined effects of the evolution of a chemical process and of spin-lattice relaxation is shown. Applied to a Diels-Alder reaction, it permitted measuring kinetics along with the effects of auto- and cross-relaxation. DNP polarization of small molecules also shows significant promise for studying protein-ligand interaction. The binding of fluorinated ligands to the protease trypsin was studied through the observation of various NMR parameter changes, such as line width, signal intensity and chemical shift of the ligands. Intermolecular polarization transfer from hyperpolarized ligand to protein can further provide information about the binding pocket of the protein. As an alternative to direct observation of protein signal, a model is presented to describe a two-step intermolecular polarization transfer between competitively binding ligands mediated through the common binding pocket of the protein. The solutions of this model relate the evolution of signal intensities to the intermolecular cross relaxation rates, which depend on individual distances in the binding epitope. In summary, DNP provides incomparable sensitivity, speed and selectivity to NMR. Quantitative models such as those discussed here enable taking full advantage of these benefits for the study of chemical processes.
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Hyperpolarized Silicon Particles as In-vivo Imaging AgentsCassidy, Maja 05 October 2013 (has links)
This thesis describes the development of hyperpolarized silicon particles as a new type of magnetic resonance imaging (MRI) agent. Silicon particles are inexpensive, non-toxic, biodegradable, targetable, and have unique physical properties that lead to extremely long nuclear polarization times. The \(^{29}Si\) nuclei are hyperpolarized by low temperature dynamic nuclear polarization using naturally occurring defects at the particle surface and directly imaged using \(^{29}Si\) MRI. The imaging window achievable is several orders of magnitude longer than other hyperpolarized imaging agents. The technique requires no additional imaging agent to be incorporated into the silicon, and so toxicity complications are reduced. The construction of a system for low temperature dynamic nuclear polarization and a NMR spectrometer for studying the nuclear polarization dynamics in silicon particles is described. Room temperature nuclear spin relaxation \((T_1)\) times are investigated for a variety of silicon particles spanning five orders of magnitude in mean diameter, from 10nm nanoparticles to mm-scale granules. The nuclear \(T_1\) times of all Si particles are found to be long, ranging from many minutes to several hours at room temperature. \(T_1\) is found to be a function of particle size, dopant concentration, synthesis method and crystallinity. A core-shell model to describe the electron and nuclear spin dynamics in the particles is developed. The decay in nuclear hyperpolarization is studied as a function of ambient magnetic field and temperature, demonstrating that the long spin relaxation times persist despite changing environmental conditions. A new technique is reported for enhancing the dynamic nuclear polarization in silicon particles using modulated microwave irradiation. A theoretical model for understanding this enhanced polarization process is developed. As well as providing an efficient mechanism for polarizing the \(^{29}Si\) nuclei within the particle, the surface defects are also found to be efficient at polarizing \(^1H\) nuclei in frozen solutions surrounding the particles. Several in-vivo applications of hyperpolarized \(^{29}Si\) MRI are demonstrated, including gastrointestinal imaging, intravenous imaging and mapping blood flow in a tumor. The spin relaxation rates are found to be unaffected by surface functionalization, the particles tumbling in solution, or the in-vivo environment. / Engineering and Applied Sciences
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