The Pathology of Adrenocortical Hyperfunction and the In Vitro Biosynthesis of Adrenal Androgens

Abstract Not Provided

Doctor of Philosophy

dissertationNewly discovered, noncoding RNA regulate cellular processes and gene expression. Simple model systems, such as quorum sensing systems, are studied to understand the mechanisms by which these RNA act on their targets. Quorum sensing is a process by which bacteria coordinate expression of their genes based on the local cell-population density. Up to five noncoding RNA, called small RNA (sRNA), in the quorum sensing systems of Vibrio harveyi and Vibrio cholerae regulate expression of the master transcriptional regulator, LuxR (V. harveyi ) and HapR (V. cholerae). LuxR/HapR regulate genes associated with virulence and bioluminescence that are downstream of the quorum sensing system. The V. harveyi and V. cholerae quorum sensing systems are topologically identical and their components are homologous, yet each responds differently under identical experimental conditions. Experiments show that all sRNA are necessary in V. harveyi and any single sRNA is sufficient in V. cholerae to repress bioluminescence. Hence, Qrr are additive in V. harveyi and redundant in V. cholerae. Subsequent experiments have shown that feedback in the sRNA circuit increases the expression of Qrr when one or more Qrr are removed. Differences in the tuning of this feedback are thought to cause the additive and redundant Qrr phenotypes; however, this long-standing hypothesis remains untested. In this work, a novel model of the V. harveyi and V. cholerae sRNA circuit is formulated and parameterized to identify parametric differences underlying the phenotypic differences. This yields a single model with two different parameterizations whose behavior agrees quantitatively with a variety of empirical data from V. harveyi and V. cholerae. The model, therefore, can be used for the in silico design, testing, and analysis of experiments and, as such, is a utility to generate experimentally verifiable hypotheses. Analysis of the model shows that the feedback in the sRNA circuit is neither necessary nor sufficient to explain the phenotypic differences, which is in contrast to the long-standing hypothesis. Rather, the additive and redundant Qrr phenotypes are emergent phenomena and, in the case of V. harveyi and V. cholerae, reflect differences in the saturation of the protein chaperon Hfq with sRNA. Overall, this suggests that Hfq is an important modulator of sRNA-facilitated repression of target mRNA

A superconducting qubit as a quantum transformer routing entanglement between a microscopic quantum memory and a macroscopic resonator

We demonstrate experimentally the creation and measurement of an entangled state between a microscopic two level system and a macroscopic superconducting resonator where their indirect interaction is mediated by an artificial atom, a superconducting persistent current qubit (PCQB). We show that the microscopic two level system, formed by a defect in an oxide layer, exhibits an order of magnitude longer dephasing time than the PCQB, while the dephasing time of the entangled states between the microscopic two level system and macroscopic superconducting resonator is significantly longer than the dephasing time in the persistent current qubits. This demonstrates the possibility that a qubit of moderate coherence properties can be used in practice to address low decoherence quantum memories by connecting them to macroscopic circuit QED quantum buses, leading future important implications for quantum information processing tasks.Comment: 4 figure

Transforming Novice Learners into Experts through Performance, Reproduction, and Representation: A Performance Studies Analysis of High-Fidelity Simulation in Healthcare Education

Ph.D

Seasonality and heterogeneity of live fish movements in Scottish fish farms

Movement of live animals is a key contributor to disease spread. Farmed Atlantic salmon Salmo salar, rainbow trout Onchorynchus mykiss and brown/sea trout Salmo trutta are initially raised in freshwater (FW) farms; all the salmon and some of the trout are subsequently moved to seawater (SW) farms. Frequently, fish are moved between farms during their FW stage and sometimes during their SW stage. Seasonality and differences in contact patterns across production phases have been shown to influence the course of an epidemic in livestock; however, these parameters have not been included in previous network models studying disease transmission in salmonids. In Scotland, farmers are required to register fish movements onto and off their farms; these records were used in the present study to investigate seasonality and heterogeneity of movements for each production phase separately for farmed salmon, rainbow trout and brown/sea trout. Salmon FW-FW and FW-SW movements showed a higher degree of heterogeneity in number of contacts and different seasonal patterns compared with SW-SW movements. FW-FW movements peaked from May to July and FW-SW movements peaked from March to April and from October to November. Salmon SW-SW movements occurred more consistently over the year and showed fewer connections and number of repeated connections between farms. Therefore, the salmon SW-SW network might be treated as homogeneous regarding the number of connections between farms and without seasonality. However, seasonality and production phase should be included in simulation models concerning FW-FW and FW-SW movements specifically. The number of rainbow trout FW-FW and brown/sea trout FW- FW movements were different from random. However, movements from other production phases were too low to discern a seasonal pattern or differences in contact pattern

The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes

Ambra1 is considered an autophagy and trafficking protein with roles in neurogenesis and cancer cell invasion. Here, we report that Ambra1 also localizes to the nucleus of cancer cells, where it has a novel nuclear scaffolding function that controls gene expression. Using biochemical fractionation and proteomics, we found that Ambra1 binds to multiple classes of proteins in the nucleus, including nuclear pore proteins, adaptor proteins such as FAK and Akap8, chromatin-modifying proteins, and transcriptional regulators like Brg1 and Atf2. We identified biologically important genes, such as Angpt1, Tgfb2, Tgfb3, Itga8, and Itgb7, whose transcription is regulated by Ambra1-scaffolded complexes, likely by altering histone modifications and Atf2 activity. Therefore, in addition to its recognized roles in autophagy and trafficking, Ambra1 scaffolds protein complexes at chromatin, regulating transcriptional signaling in the nucleus. This novel function for Ambra1, and the specific genes impacted, may help to explain the wider role of Ambra1 in cancer cell biology

Kinematics and helicity evolution of a loop-like eruptive prominence

We aim at investigating the morphology, kinematic and helicity evolution of a loop-like prominence during its eruption. We use multi-instrument observations from AIA/SDO, EUVI/STEREO and LASCO/SoHO. The kinematic, morphological, geometrical, and helicity evolution of a loop-like eruptive prominence are studied in the context of the magnetic flux rope model of solar prominences. The prominence eruption evolved as a height expanding twisted loop with both legs anchored in the chromosphere of a plage area. The eruption process consists of a prominence activation, acceleration, and a phase of constant velocity. The prominence body was composed of left-hand (counter-clockwise) twisted threads around the main prominence axis. The twist during the eruption was estimated at 6pi (3 turns). The prominence reached a maximum height of 526 Mm before contracting to its primary location and partially reformed in the same place two days after the eruption. This ejection, however, triggered a CME seen in LASCO C2. The prominence was located in the northern periphery of the CME magnetic field configuration and, therefore, the background magnetic field was asymmetric with respect to the filament position. The physical conditions of the falling plasma blobs were analysed with respect to the prominence kinematics. The same sign of the prominence body twist and writhe, as well as the amount of twisting above the critical value of 2pi after the activation phase indicate that possibly conditions for kink instability were present. No signature of magnetic reconnection was observed anywhere in the prominence body and its surroundings. The filament/prominence descent following the eruption and its partial reformation at the same place two days later suggest a confined type of eruption. The asymmetric background magnetic field possibly played an important role in the failed eruption.Comment: 9 pages, 8 figures, in press in A&

Health Workers' Performance in the Implementation of Patient Centred Tuberculosis Treatment (PCT) Strategy Under Programmatic Conditions in Tanzania: A Cross Sectional Study.

Patient Centred Tuberculosis Treatment (PCT) is a promising treatment delivery strategy for Mycobacterium tuberculosis (TB). It aims to improve adherence to treatment by giving patients the choice of having drug intake supervised at the health facility by a medical professional or at home by a supporter of their choice. A cross-sectional survey was undertaken in three districts of Tanzania during October 2007, one year after PCT was rolled out nationally. Semi-structured questionnaires were used to assess whether key elements of the PCT approach were being implemented, to evaluate supporters' knowledge, to capture opinions on factors contributing to treatment completion, and to assess how treatment completion was measured. Transcripts from open-ended responses were analysed using framework analysis. Interviews were conducted with 127 TB patients, 107 treatment supporters and 70 health workers. In total, 25.2% of TB patients were not given a choice about the place of treatment by health workers, and only 13.7% of those given a choice reported that they were given adequate time to make their decision. Only 24.3% of treatment supporters confirmed that they were instructed how to complete patients' treatment cards. Proper health education was the factor most frequently reported by health workers as favouring successful completion of TB treatment (45.7%). The majority of health workers (68.6%) said they checked returned blister packs to verify whether patients had taken their treatment, but only 20.0% checked patients' treatment cards. The provision of choice of treatment location, information on treatment, and guidance for treatment supporters need to be improved. There is a requirement for regular re-training of health workers with effective supportive supervision if successful implementation of the PCT approach is to be sustained

Readfish enables targeted nanopore sequencing of gigabase-sized genomes

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Nanopore sequencers can be used to selectively sequence certain DNA molecules in a pool by reversing the voltage across individual nanopores to reject specific sequences, enabling enrichment and depletion to address biological questions. Previously, we achieved this using dynamic time warping to map the signal to a reference genome, but the method required substantial computational resources and did not scale to gigabase-sized references. Here we overcome this limitation by using graphical processing unit (GPU) base-calling. We show enrichment of specific chromosomes from the human genome and of low-abundance organisms in mixed populations without a priori knowledge of sample composition. Finally, we enrich targeted panels comprising 25,600 exons from 10,000 human genes and 717 genes implicated in cancer, identifying PML–RARA fusions in the NB4 cell line i

Entanglement, Mixedness, and Spin-Flip Symmetry in Multiple-Qubit Systems

A relationship between a recently introduced multipartite entanglement measure, state mixedness, and spin-flip symmetry is established for any finite number of qubits. It is also shown that, within those classes of states invariant under the spin-flip transformation, there is a complementarity relation between multipartite entanglement and mixedness. A number of example classes of multiple-qubit systems are studied in light of this relationship.Comment: To appear in Physical Review A; submitted 14 May 200