This thesis describes the development of a multi-sensor, multi-energy x-ray prototype for automated explosives detection. The system is based on the American Science and Engineering model 101ZZ x-ray system. The 101ZZ unit received was an early model and lacked documentation of the many specialized electronic components. X-ray image quality was poor. The system was significantly modified and almost all AS&E system electronics bypassed: the x-ray source controller and conveyor belt motor were made computer controllable; the x-ray detectors were re-positioned to provide forward scatter detection capabilities; new hardware was developed to interface to the AS&E pre-amplifier boards, to collect image data from all three x-ray detectors, and to transfer the data to a personal computer. This hardware, the Differential Pair Interface Board (DPIB), is based on a Field Programmable Gate Array (FPGA) and can be dynamically re-configured to serve as a general purpose data collection device in a variety of applications. Software was also developed for the prototype system. A Windows NT device driver was written for the DPIB and a custom bus master DMA collection device. These drivers are portable and can be used as a basis for the development of other Windows NT drivers. A graphical user interface (GUI) was also developed. The GUI automates the data collection tasks and controls all the prototype system components. It interfaces with the image processing software for explosives detection and displays the results. Suspicious areas are color coded and presented to the operator for further examination. / Master of Science

In-vehicle navigation systems (IVNS) have the potential to benefit older drivers, reducing stress associated with way-finding and providing on-trip support, especially in unfamiliar locations. However, existing IVNS present challenges to usability, resulting in lack of uptake and over-reliance on pre-trip planning. This paper presents research aimed at identifying features that make IVNS user-friendly and appropriate for older drivers. Studying navigational performance within a simulated driving environment, it focuses on the use of landmarks with route guidance information, and the most appropriate method of information provision (audio only, visual only or a combination of audio and visual). It also assesses potential gender differences that might arise with landmark-based navigational information. Solutions include use of appropriate roadside landmarks, and information delivered through a combination of audio and icon-based visual format. These features result in lower workload and fewer navigational errors. The audio/visual modality reduces the hazard of distraction by landmarks resulting in fewer visual glances and lower glance duration to the roadside compared to other modalities. Design and provision of IVNS tailored to older drivers’ needs can make a considerable contribution to maintaining individual mobility for longer.

Due to intensive coastal development, a combination of local (e.g. pollution, fishing) and global pressures (such as climate change) is affecting marine habitats worldwide. This is a pressing issue in Saudi Arabia, particularly considering the plans for the expansion of sea-related activities within the Saudi Arabia's Vision 2030 framework. Sustaining some of those activities, such as tourism, is dependent upon the maintenance of good ecosystem health. National monitoring programs in Saudi Arabia are scarce and a lack of sound knowledge on how marine organisms change in space and time and what the main factors driving their responses are, limits the contribution of scientists to the management and conservation of the Red Sea. Here we provide baseline knowledge, that can be critical for assessing changes associated with current and future coastal development as well as climate change by collecting data across multiple spatial (including multiple habitats) and temporal scales for the analysis of macroinvertebrate organisms and environmental drivers. One of the most striking findings is related to the low densities observed for macroinvertebrates, making populations potentially vulnerable to disturbance. We also highlight the contribution of different habitats within the seascape and the need to prioritize the features of the bottoms for management and conservation purposes. Each habitat has a unique ecological signature but they are connected to adjacent habitats through a subset of species able to utilize different biotopes within the seascape. Disrupting this ecological network may affect biodiversity patterns from local to regional levels. Within each habitat, temporal variability should be taken into account as patterns change on a seasonal and annual scale. The aim of the thesis is to contribute to the sustainable development of the Red Sea, a unique resource shared among several countries, which will result in a long-term benefit to the Kingdom of Saudi Arabia, and other countries. Information provided is critical as previous knowledge for the region was almost inexistent and allows for future studies to investigate and predict the impacts of intense coastal development and inform conservation and management decisions.

abstract: Phenotypic and molecular profiling demonstrates a high degree of heterogeneity in the breast tumors. TP53 tumor suppressor is mutated in 30% of all breast tumors and the mutation frequency in basal-like subtype is as high as 80% and co-exists with several other somatic mutations in different genes. It was hypothesized that tumor heterogeneity is a result of a combination of neo-morphic functions of specific TP53 driver mutations and distinct co-mutations or the co-drivers for each type of TP53 mutation. The 10 most common p53 missense mutant proteins found in breast cancer patients were ectopically expressed in normal-like mammary epithelial cells and phenotypes associated with various hallmarks of cancer examined. Supporting the hypothesis, a wide spectrum of phenotypic changes in cell survival, resistance to apoptosis and anoikis, cell migration, invasion and polarity was observed in the mutants compared to wildtype p53 expressing cells. The missense mutants R248W, R273C and Y220C were most aggressive. Integrated analysis of ChIP and RNA seq showed distinct promoter binding profiles of the p53 mutant proteins different than wildtype p53, implying altered transcriptional activity of mutant p53 proteins and the phenotypic heterogeneity of tumors. Enrichment and model-based pathway analyses revealed dysregulated adherens junction and focal adhesion pathways associated with the aggressive p53 mutants. As several somatic mutations co-appear with mutant TP53, we performed a functional assay to fish out the relevant collaborating driver mutations, the co-drivers. When PTEN was deleted by CRISPR-Cas9 in non-invasive p53-Y234C mutant cell, an increase in cell invasion was observed justifying the concept of co-drivers. A genome wide CRISPR library-based screen on p53-Y234C and R273C cells identified separate candidate co-driver mutations that promoted cell invasion. The top candidates included several mutated genes in breast cancer patients harboring TP53 mutations and were associated with cytoskeletal and apoptosis resistance pathways. Overall, the combined approach of molecular profiling and functional genomics screen highlighted distinct sets of co-driver mutations that can lead to heterogeneous phenotypes and promote aggressiveness in cells with different TP53 mutation background, which can guide development of novel targeted therapies. / Dissertation/Thesis / Doctoral Dissertation Biochemistry 2019

The importance of environmental analysis in the strategic management process and the effects of economic value drivers on firm or industry performance have been discussed conceptually and empirically by researchers in corporate failure, and in the areas of finance, accounting, strategic management, and the hospitality industry in the past. The belief is that the more systematic and frequent the scanning performed by managers the higher the chances of improving the firm's or industry's performance. The present study is an attempt to identify economic value drivers that impact the casual theme sector of the restaurant industry and to ascertain the degree of the impact during the period 1994-2003. The statistical analysis was based on time series data, using Cross Correlation, Granger Causality, and Multivariate Regression. An exhaustive range of economic value drivers within ten categories were tested: commodity market; foreign currency market; labor market; inflation; stock market; national income and output; interest rate; government revenue, spending, debt, and taxes; money supply; and consumer spending. The unit of analysis was done at the industry level, and an index of operational cash flows of the casual theme sector of the restaurant industry was developed. Economic value drivers within the categories of commodity markets, labor markets, inflation, stock market, national input/output, government revenue/spending/debt/taxes, money markets, and consumer spending indicated co-movements with and causality to the index of operational cash flows per unit in the casual theme restaurant industry. A high variance in the operational cash flows in the casual theme restaurant industry was explained by a set of economic value drivers within commodity markets, inflation, and labor markets. In broad, practical terms, the study intends to support the importance of assessing the economic environment for better performance of the restaurant industry and to provide food service managers with a conceptual model to understand the unanticipated effects on the performance of existing or new strategies. In real terms, the model and set of economic value drivers in the model would help them decide what kinds of action or investment in a firm or industry's weakness should be taken to buffer future operational risks against value drivers within economic environment. / Master of Science

The thesis is aimed at the development of Scanning Probe Microscopes (SPM). It describes design and development of modular controll electronics to be applied eectively on more microscopes SPM. Control electronics consist of stabilized power source, high–voltage amplier and probe signal amplier. The open–source project GXSM has been introduced. It contains a logic control unit which controls scanning, acquiring data and feedback control. GXSM provides a graphical user interface based on linux operation system. Second part of the thesis is aimed at design and development of interferometric deection sensing system for SPM cantilevers and applications at SPM in general. Designed interferometer has been assembled and tested. It can clearly distinguish a signal of amplitude 2 nm. At the end of the thesis the design of interferometric system implementation is presented.

No description available.

Southern Appalachian wetlands have yet to be studied in terms of net primary production (NPP), thus few studies have been conducted to examine what environmental factors have relationships with NPP. To that end, this research investigates several facets of southern Appalachian wetland production. The research was divided into three studies. The first study was conducted to answer the question of what environmental factors have relationships with NPP. It appears that stream discharge and annual precipitation had the strongest relationships with NPP (r = 0.91, p <0.05 and r = 0.81, p <0.05, respectively), yet both factors showed multicolinearity (r = 0.97, p <0.05). The strong relationships between hydrologic factors and NPP is similar to montane wetlands in the western United States. The second study was conducted to examine the relationship between water chemistry and NPP. Calcium (Ca), Magnesium (Mg), and pH were examined in order to determine if any of the aforementioned factors had a relationship with NPP. Neither Ca (r = -0.34, p = 0.0835) nor Mg (r =-0.38, p = 0.0535) had strong relationships with NPP, though pH (r = -0.66, p <0.05) had a strong negative relationship with NPP. The acidity of the stream water, driven by the acid rain in the southern Appalachians, creates enhanced conditions for wetland plants to grow. The third study was conducted to establish which vegetation index was best for estimating NPP from proximally and remotely sensed data. The findings suggest that VARIRed Edge was best for examining NPP at the in situ level, NDVI was best for examining NPP at the airborne level, and the DVI was the best for examining NPP at the satellite level. NPP in southern Appalachian wetlands is driven by the chemistry, specifically the pH, of stream discharge and annual precipitation and can be monitored by NDVI using NAIP data or DVI using Landsat data. The examination of NPP in southern Appalachians in response to environmental factors and water chemistry along with the examination of vegetation indices at three levels of platforms will help to monitor and manage these rare and unique ecosystems in the future.

No description available.

Brain metastasis (BM), the most common tumor of the central nervous system, occurs in 20-36% of primary cancers. In particular, 20-40% of patients with non-small cell lung cancer (NSCLC) develop brain metastases, with a dismal survival of approximately 4-11 weeks without treatment, and 16 months with treatment. This highlights a large unmet need to develop novel targeted therapies for the treatment of lung-to-brain metastases (LBM). Genomic interrogation of LBM using CRISPR technology can inform preventative therapies targeting genetic vulnerabilities in both primary and metastatic tumors. Loss-of-function studies present limitations in metastasis research, as knocking out genes essential for survival in the primary tumor cells can thwart the metastatic cascade prematurely. However, transcriptional overexpression of genes using CRISPR activation (CRISPRa) has the potential for overcoming dependencies of gene essentiality. In this thesis, we created and utilized an in vivo genome-wide CRISPRa screening platform to identify novel genes, that when overexpressed, drive LBM. We have developed a patient-derived orthotopic murine xenograft model of LBM using a patient-derived NSCLC cell line (termed CRUK cells) from the Swanton Lab TRACERx study. We introduced a human genome-wide CRISPRa single guide RNA (sgRNA) library into non-metastatic and pro-metastatic lung cancer CRUK cells to achieve 500X representation of each sgRNA in the activation library. We then injected the cells into the lungs of immunocompromised mice and tracked lung tumor development and BM formation. Upon sequencing primary lung tumors and subsequent BM, we will identify enriched sgRNAs which may represent novel drivers of primary lung tumor formation and LBM. To the best of our knowledge, this study is the first in vivo genome-wide CRISPR activation screen using patient-derived NSCLC cells to help elucidate drivers of LBM. This work serves to provide a framework to gain a deeper understanding of the regulators of BM formation which will hopefully lead to targeted drug discovery that will ultimately be used in clinical trials to help eradicate brain metastasis in NSCLC patients. / Thesis / Master of Science (MSc) / Brain metastasis, or the spread of a primary cancer from another organ to the brain, is the most common adult brain tumor. Brain metastases can arise after the treatment of primary tumors and are only detected in the clinic at a highly malignant stage. Current treatments for brain metastasis consist of surgical removal and palliative chemoradiotherapy, which fail to fully eliminate the brain tumor. Over 20% of cancer patients develop brain metastases, with lung, breast, and skin cancers leading as the top three sources of metastasis. In particular, 40% of patients with non-small cell lung cancer develop brain metastasis, with survival of only 4-11 weeks once diagnosed without treatment, and 16 months with treatment. As systemic therapies for the treatment of non-small cell lung cancer are becoming increasingly effective at controlling primary disease, patients are ironically succumbing to their brain tumors. This highlights a large unmet need to develop novel targeted therapies for the treatment of lung-to-brain metastases (LBM). Functional genomic tools provide the opportunity to investigate the genetic underpinnings of LBM. With the advent of gene editing technologies, we are able to overexpress various genes and observe the impact genetic perturbations have on tumor initiation, growth, and metastasis. In this thesis, we devised a pre-clinical animal model of LBM that could be used to study genetic drivers of LBM using a gene overexpression tool such that one gene per tumor cell gets activated. We are then able to model the disease trajectory from a lung tumor to brain metastasis development using patient samples in our animal model and identify genes that, upon overexpression, drive LBM. This platform will lead to potential therapeutic targets to prevent the formation of LBM and prolong the survival of patients with non-small cell lung cancer.