The concept of open-access networks appeals to communities that want to invest in and improve their access to modern telecommunications services. By investing in, or building their own open-access telecommunications networks, communities can create an environment where several telecommunications service providers can co-exist on a common open-access infrastructure. This model promotes innovation and competition among several smaller service providers rather than having a monopoly or oligopoly from those companies that can afford the investment of infrastructure in the community. This research provides an analysis of two large open-access fiber-to-the-home networks in Utah to determine a set of recommendations and best-practices for other communities that are considering building their own community networks. The networks analyzed in this research are the Utah Telecommunications Open Infrastructure Agency (UTOPIA) and the Provo City network (iProvo).

Triple Modular Redundancy (TMR) is a common reliability technique for mitigating single event upsets (SEUs) in FPGA designs operating in radiation environments. For FPGA systems that employ configuration scrubbing, majority voters are needed in all feedback paths to ensure proper synchronization between the TMR replicates. Synchronization voters, however, consume additional resources and impact system timing. This work introduces and contrasts seven algorithms for inserting synchronization voters while automatically performing TMR. The area cost and timing impact of each algorithm on a number of circuit benchmarks is reported. The work demonstrates that one of the algorithms provides the best overall timing performance results with an average 8.5% increase in critical path length over a triplicated design without voters and a 29.6% area increase. Another algorithm provides far better area results (an average 3.4% area increase over a triplicated design without voters) at a slightly higher timing cost (an average 14.9% increase in critical path length over a triplicated design without voters). In addition, this work demonstrates that restricting synchronization voter locations to flip-flop output nets is an effective heuristic for minimizing the timing performance impact of synchronization voter insertion.

Eribulin is a non-taxane microtubule inhibitor approved for the treatment of metastatic breast carcinoma after two prior chemotherapeutic regimens. We report a patient with extended progression-free survival (PFS) of more than 57 months with metastatic breast carcinoma treated with eribulin in the third-line setting. A 48-year-old lady was diagnosed with stage IIA (pT2N0M0), high grade, triple-negative, invasive ductal carcinoma (IDC) of the left breast on core needle biopsy. She underwent neoadjuvant chemotherapy with adriamycin, and cyclophosphamide followed by a negative sentinel lymph node (SLN) biopsy. Subsequent mastectomy and axillary lymph node dissection revealed a 2.5 cm, high grade, triple-negative IDC with three additional lymph nodes negative for metastatic carcinoma, consistent with the initial diagnosis. Eight months into the surveillance program, the patient developed a 2.8 cm right lower lobe (RLL) lung mass with standard uptake value (SUV) of 27 on positron emission tomography-computed tomography (PET/CT). Core needle biopsy of the lung lesion revealed sheets of poorly differentiated carcinoma, immunophenotypically compatible with the initial diagnosis of breast pathology. She then commenced single-agent paclitaxel in the 1st line metastatic setting with a significant decrease in RLL lung mass to less than 1 cm with an SUV of 1.7 noted. The patient developed progression after seven months and started 2nd line gemcitabine noting initial improvement and subsequent stable disease for a period of 12 months. Eventual progression of RLL lung nodule measuring 2.1 cm with SUV of 10 noted. Initiated 3rd line eribulin with a notable response on imaging studies within three months and with no evidence of disease (NED) on scans over the subsequent 57 months. Eribulin related mild neuropathy superimposed on previous paclitaxel associated grade 2 neuropathy required a 20% eribulin dose reduction. The patient is currently clinically and radiographically stable with plateaued serum tumor markers. Our patient has shown excellent response and tolerance to eribulin with PFS of over 57 months (nineteen times the norm) which is rare.

The extension of the theory for two dimensional turbulent boundary layers into three dimensional flows has met with limited success. The failure of the extended models is attributed to the anisotropy of the turbulence. This is seen by the turbulent shear stress angle lagging the flow gradient angle and by the behavior of the Reynolds shear stresses lagging that of the mean flow. Transport equations for the turbulent shear stresses were proposed to be included in a modeling effort capable of accounting for the lags seen in the flow. This study is aimed at developing algebraic relationships between the various Reynolds-averaged terms in these modeling equations. Particular emphasis was placed on the triple products that appear in the transport equations. Eleven existing experimental data sets were acquired from the original authors and re-examined with respect to developed and existing parameters. A variety of flow geometries were collected for comparison. Emphasis was placed on experiments that included all six components of the Reynolds stress tensor and triple products. Parameters involving the triple products are presented that appear to maintain a relatively constant value across regions of the boundary layer. The variation of these parameters from station to station and from flow to flow is discussed. Part of this study was dedicated to parameters that were previously introduced, but never examined with respect to the data that was collected. Results of these parameters are presented and discussed with respect to agreement or disagreement with the previous results. The parameters presented will aid in the modeling of three dimensional turbulent boundary layers especially with models that employ the transport equations for the Reynolds stresses. / Master of Science

This thesis is a study of the effects of distributed roughness elements on a two-dimensional turbulent boundary layer. Measurements were taken on a total of ten rough wall configurations: four involving Gaussian spikes, and six with circular cylindrical posts. Rough wall flows are particularly suited to study with Laser Doppler Velocimetry (LDV) due to the fact that measurements are required near a solid surface, as well has in highly turbulent fluid. The LDV system used in this study is a fine resolution (~50 micron), three-component, fiber optic system. All mean velocities, Reynolds stresses, and triple products are measured. This study is unique in the range and variety of roughness cases for which data was taken. The data show that the flow over a rough wall is characterized by high levels of turbulence near the roughness element peaks at the interface between low-speed, near-wall fluid and the higher speed fluid above. Behind an element, high-momentum fluid sweeps toward the wall, and there is a small region of ejection of low-momentum fluid. Cylindrical elements typically have larger magnitudes of turbulent stresses at their peaks compared to Gaussian elements. Trends in mean velocity profile parameters such as displacement height, roughness effect, and wake parameter are examined with respect to roughness element geometry and spacing. / Master of Science

Breast cancer tops the list of new cancer cases and is predicted to be the second leading cause of cancer deaths in women in 2012. The primary objective of the present study was to provide insights into the molecular mechanisms underlying the aggressive growth and metastasis of triple-negative and basal-like breast cancers. To study increased growth and invasive behavior in triple-negative and basal-like breast cancers we utilize both an interesting and relevant cell culture model and examination of human tissue. In this study, we use the Tamoxifen-selected, MCF-7 derivative, TMX2-28 breast cancer cell line. TMX2-28 cells are triple-negative in that they lack expression of the estrogen receptor alpha (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). They also have acquired a mixed basal/luminal cytokeratin profile, suggestive of a more basal-like phenotype. TMX2-28 cells are highly proliferative and invasive. In addition to our cell culture model, we also examine human tissue. Thirty frozen breast carcinoma samples were evaluated for mRNA expression. Additionally, I analyzed protein expression, using immunohistochemistry (IHC), of 50 benign reduction mammoplasty and 188 breast tumors (formalin-fixed paraffin embedded). Of the 188 breast tumors, 93 were ERα-positive and 95 were ERα-negative. Of the 95 ERα-negative samples, 24 were further classified as non-triple negative (either PR or HER2 positive), 49 were classified as triple-negative, and 22 were not further classified due to unavailability of HER2 status and were used only in analyses of ERα-negative tumors. Thirty-seven of the 188 tumor samples were ductal carcinoma in situ, 138 were invasive ductal carcinomas, and 13 were classified as other. Lastly, 23 of the 188 tumors were grade 1, 48 were grade 2, 105 were grade 3, and 12 did not have grade data available. S-phase kinase-associated protein 2 (SKP2) plays an important role in cell cycle regulation by targeting p27 for degradation. The cyclin-dependent kinase (CDK) inhibitor p27 regulates G1/S transition by binding cyclin/CDK complexes and abrogating its activity. By targeting p27 for degradation, SKP2 frees the complexes needed to progress into the S phase of the cell cycle. Evaluation of SKP2 expression in TMX2-28 revealed significantly higher levels than in other breast cancer cell lines. Despite the high levels of SKP2 expression, p27 protein was not reduced. However, levels of the Serine 10 phosphorylated form of p27 (pSer10p27), which has been associated with increased proliferation rates, was found to be increased. Furthermore, suppression of SKP2 completely eliminated the pSer10p27 and slowed cycle progression confirming the role of SKP2 in the aggressive growth of TMX2-28 cells. Assessment of mRNA from 30 frozen human breast cancers demonstrated that SKP2 is more highly expressed in ERα-negative and basal-like breast cancers. Immunohistochemical analysis of 188 breast cancers and 50 benign reduction mammoplasty tissues confirmed that SKP2 is more highly expressed in ERα-negative breast cancers and for the first time demonstrated that triple-negative breast cancers are more likely to overexpress SKP2 than are non-triple-negative, but still ERα-negative, tumors. In contrast to some previous reports, we did not observe an inverse relationship between SKP2 and p27 expression. Only 11% of tumors expressed high SKP2 and low p27, while 32% of tumors had high SKP2 and high p27. Although no significant relationship between SKP2 and p27 expression was observed in human breast cancers, a significant positive relationship was discovered between SKP2 and pSer10p27. Furthermore, high levels of SKP2 and pSer10p27 were observed significantly more often in ERα-negative and triple negative breast tumors than in ERα-positive breast cancers. Based on these results and those of the cell culture experiments showing complete elimination of pSer10p27 after suppression of SKP2 it appears that levels of pSer10p27 may be a better indicator of SKP2-dependent p27 degradation than are levels of p27. Therefore, that inhibiting SKP2 in triple-negative breast cancers expressing high levels of both SKP2 and pSer10p27 regardless of p27 levels may be a valid therapeutic approach. A foremost threat to patients is tumor invasion and metastasis, with the greatest risk to patients diagnosed with triple-negative and basal-like breast cancers. Two distinct morphological/functional mechanisms are known for single cell migration in tissues: mesenchymal and amoeboid invasion. Mesenchymal movement involves the use of proteases that cause cellular lysis in tissues, thereby creating a path through which cells can invade. Amoeboid movement is protease-independent; cells find paths through the ECM by pushing and squeezing through regions of adequate size. Despite their invasive phenotype, TMX2-28 retains morphology similar to non-aggressive MCF-7 cells, suggesting that their invasion may be proteolytic-independent. We determined that TMX2-28 lack MMP-1 mRNA, and MMP-2/MMP-9 protein expression; each of which is important in protease-dependent invasion. Furthermore, TMX2-28 cells have low expression of other genes key to protease-dependent invasion including Slug, Zeb 1, Zeb 2, Vimentin, Fibronectin and N-cadherin. RhoA is a member of the Rho superfamily of GTPases that acts as a molecular switch to control signal transduction and is critical to the amoeboid invasion mechanism. TMX2-28 cells have high expression of protease-independent invasion genes such as RhoA, ROCK 1, ROCK 2, and E-cadherin. Finally, treating TMX2-28 cells with a RhoA pathway inhibitor or an shRNA targeting RhoA significantly reduces their invasiveness. These data suggest that TMX2-28 cells use a RhoA-dependent, proteolytic-independent invasion mechanism. Collectively, the data presented here demonstrate the roles of SKP2 and RhoA in triple-negative and basal-like breast cancers, making both genes, as well as their pathways, desirable therapeutic targets.

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Sodium (23Na) plays a pivotal role in cellular homeostasis throughout all life forms. In the human body it has a plethora of physiological functions including regulation of bodily fluids, muscle contraction, neuronal transmission, and connective tissue integrity. The 23Na nucleus can be visualized using magnetic resonance imaging (MRI) because it has spin 3/2 and is the 100% naturally abundant isotope of sodium. However, unlike hydrogen (1H), the nucleus of choice for MRI scanning, 23Na MR clinical applications are almost non-existent, even though it is the second most MR visible nucleus after 1H. This is primarily because 23Na requires its own customized hardware (i.e. radiofrequency RF coil) and software (i.e. pulse sequence/acquisition and image reconstruction techniques). Additionally, 23Na MR is challenging because of significantly lower signal-to-noise ratio (SNR), which translates to a requirement for lengthy scans and lower spatial resolution. Hence, development and optimization of 23Na MR acquisition techniques is an ongoing subject of research. In this dissertation development and optimization of approaches that exploit sodium as a biomarker for musculoskeletal health are described. Specifically, discussions of advanced 23Na MR techniques fall into two main categories: magnetic resonance imaging (MRI) and spectroscopy (MRS). The work first explored development of a MRI compatible electrical muscle stimulation (EMS) system that could be used as a consistent alternative to voluntary muscle contraction. A variety of MRI methods were used to confirm the similarity between stimulation and voluntary activation of muscles of the lower leg. In a follow- up study quantum filtered (QF) 23Na MRS was used to assess dynamic changes in skeletal muscle before, during and following voluntary exercise. Total (single quantum filtered, SQF) and bound intracellular sodium (triple quantum filtered, TQF) were measured in 9 healthy subjects with a 12s temporal resolution. Total sodium (SQF) significantly increased 4% (p < 0.01), while bound intracellular sodium content decreased 7% (p < 0.01) with exercise. Both returned to baseline following exercise; TQF after a few seconds and SQF after approximately 12 minutes (p < 0.05). In a preliminary study the MR-compatible EMS unit demonstrated similar QF 23Na MRS results. Sodium MR imaging, like typical 1H-MRI scanning, can be performed by rasterizing k-space. However, this approach is both temporally and SNR inefficient. There- fore newer optimized 23Na MRI pulse sequence approaches have been developed. The cost-benefit of extending the acquisition window length in terms of SNR gain and blurring in the in vivo 23Na MRI of the human knee was explored in 3 healthy subjects using a density adapted 3-dimensional projection reconstruction (DA-3DPR) sequence. Mean SNR doubled when the acquisition window was increased from 4 to 25ms. Concurrently, the FWHM, as a measure of cartilage blurring, increased by only 1±0mm across three different sections of articular cartilage. In a second imaging experiment, a pseudo-random 3D non-Cartesian k-space acquisition scheme for 23Na MRI was introduced. This scheme was highly effective in minimizing the aliasing artifacts leading to 9 times less number of shots required to cover k-space compared to a fully-sampled acquisition scheme. Hence, this resulted in a 9-fold reduction in scan time to cover k-space. Images of a resolution phantom and healthy human knee, with 3mm isotropic resolution (zero padded to 1mm isotropic resolution), were reconstructed using a non-uniform fast Fourier transform (NUFFT). / Dissertation / Doctor of Philosophy (PhD)

Primary care within the United States’ health care system is evolving to address increases in chronic conditions across the lifespan that impact individuals’ daily lives, and the health care system’s performance and cost. Even as interprofessional primary care teams aim to manage a large majority of health needs over time, these teams often lack the skilled professionals necessary to address function in daily life. Occupational therapy’s distinct value as experts in evaluation and intervention for health-related occupational development, adaptation, prevention and management can address this problem. However, continued education and additional tools are necessary in order for occupational therapists to increase their knowledge of the profession’s role in primary care, increase self-efficacy in promoting occupational therapy to stakeholders, and increase self-efficacy to utilize resources for research and establishing occupational therapy in primary care settings. The proposed online course "Occupational Therapy in Primary Care: What, Why, Where, & How?" is specifically targeted to occupational therapists to addresses these outcomes. Theoretical and historical evaluation of occupational therapy in primary care in the United States and Canada supports understanding the problem and mechanisms that can help navigate efforts to include occupational therapy in primary care. Diffusion of Innovations and Adult Learning Theory guide the course’s two-phases of development and dissemination. This project is a timely contribution to the emerging area of occupational therapy in primary care that supports the Institute for Health Care Improvements’ (IHI) Triple Aim to improve the individual experience of care, health of populations and reduce per capita cost of care.

One of the most critical issues of our time is sustainability. Simultaneously, techno optimism is prevailing in public discourse suggesting that technology will create a sustainable future without requiring drastic changes. Despite the connection that is often drawn between technology and sustainability and the presence of technologies in organisations, research combining the two concepts remains limited and does not account for the interplay of social values and technological artefacts. To overcome this incomplete picture of technology, this thesis employs sociomateriality to investigate how sustainability and technology are understood in relation to each other by young sustainability practitioners in for-profit organisations. Following the social constructivist philosophy, nine semi-structured interviews were conducted which show that practitioners recognise the environmental and social limits to development and use the triple bottom line (TBL), consisting of economic, environmental and social dimensions to translate sustainability into organisations. However, TBL implementation varies between organisations showing the difficulty of unifying organisational sustainability in one concept. Furthermore, young sustainability practitioners understand technology as sociomaterial, describing the interplay between an artefact’s affordances and restraints, and the practitioner’s configuration work that co-create outcomes. Moreover, the interviewees are optimists not because they rely on technology, but they believe in human’s ability to change which differs from techno optimism. It can be concluded that practitioners are critical about relying on technology for sustainability and believe that sustainability is created through an interplay of humans with technology, transferring responsibility to humans. When it comes to creating a sustainable future, they first struggled to envision an alternative future beyond technological developments but started imagining when given space to reflect. One outcome of the research is that young sustainability practitioners must be given room to reflect on their understanding of sustainability, technology and their relationship as the first step to taking actions to create the future.