Quality control of high throughput screening

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Quality control of high throughput screening

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Leveraging employee creativity through high performance work systems:a multilevel perspective

Research has looked at single rather than a configuration of human resource management (HRM) practices to influence creativity so it is not yet clear how these practices synergistically facilitate creativity and organisational performance. I address this significant but unanswered question in a three-part study. In Study 1, I develop a high performance work system (HPWS) for creativity scale. I use Study 2 sample to test the validity of the new scale. In Study 3, I test a multilevel model of the intervening processes through which branch HPWS for creativity influences creativity and branch performance. Specifically, at the branch level, I draw on social context theory and hypothesise that branch HPWS for creativity relates to climate for creativity which, in turn, leads to creativity, and ultimately, to profit. Furthermore, I hypothesise environmental dynamism as a boundary condition of the creativity-profit relationship. At the individual level, I hypothesise a cross-level effect of branch HPWS for creativity on employee-perceived HPWS. I draw on self-determination theory and argue that perceived HPWS for creativity relate to need satisfaction and the psychological pathways of intrinsic motivation and creative process engagement to predict creativity. I also hypothesise climate for creativity as a cross-level moderator of the intrinsic motivation-creativity and creative process engagement-creativity relationships. Results of hierarchical linear modeling (HLM) indicate that ten out of the fifteen hypotheses were supported. The findings of this study respond to calls for HPWS to be designed around a strategic focus by developing and providing initial validity evidence of an HPWS for creativity scale. The results reveal the underlying mechanisms through which HPWS for creativity simultaneously influences individual and branch creativity leading to profit. Lastly, results indicate environmental dynamism to be an important boundary condition of the creativity-profit relationship and climate for creativity as a cross-level moderator of the creative process engagement-creativity.

Achieving low cost and high quality aero structure assembly through integrated digital metrology systems

Measurement assisted assembly (MAA) has the potential to facilitate a step change in assembly efficiency for large structures such as airframes through the reduction of rework, manually intensive processes and expensive monolithic assembly tooling. It is shown how MAA can enable rapid part-to-part assembly, increased use of flexible automation, traceable quality assurance and control, reduced structure weight and improved aerodynamic tolerances. These advances will require the development of automated networks of measurement instruments; model based thermal compensation, the automatic integration of 'live' measurement data into variation simulation and algorithms to generate cutting paths for predictive shimming and drilling processes. This paper sets out an architecture for digital systems which will enable this integrated approach to variation management. © 2013 The Authors.

A stable graph-based representation for object recognition through high-order matching

Many Object recognition techniques perform some flavour of point pattern matching between a model and a scene. Such points are usually selected through a feature detection algorithm that is robust to a class of image transformations and a suitable descriptor is computed over them in order to get a reliable matching. Moreover, some approaches take an additional step by casting the correspondence problem into a matching between graphs defined over feature points. The motivation is that the relational model would add more discriminative power, however the overall effectiveness strongly depends on the ability to build a graph that is stable with respect to both changes in the object appearance and spatial distribution of interest points. In fact, widely used graph-based representations, have shown to suffer some limitations, especially with respect to changes in the Euclidean organization of the feature points. In this paper we introduce a technique to build relational structures over corner points that does not depend on the spatial distribution of the features. © 2012 ICPR Org Committee.

Development of an instrument to measure high school students' global awareness and attitudes: Looking through the lens of social sciences

The purpose of this study was to develop an instrument to measure high school students’ perspectives on global awareness and attitudes toward social issues. The research questions that guided this study were: (a) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' global awareness? (b) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' attitudes towards global social issues? (c) What is the relationship between high school students’ GPA, race/ethnicity, gender, socio-economic status, parents’ education, getting the news, reading and listening habits, the number of classes taken in the social sciences, whether they speak a second language, and have experienced living in or visiting other countries, and their perception of global awareness and attitudes toward global social issues. ^ An ex post facto research design was used and the data were collected using a 4-part Likert-type survey. It was administered to 14 schools in the Miami-Dade County, Florida area to 704 students. A factor analysis with an orthogonal varimax rotation was vii used to select the factors that best represented the three constructs – global education, global citizenship, and global workforce. This was done to establish construct validity. Cronbach’s alpha was used to determine the reliability of the instrument. Descriptive statistics and a hierarchical multiple regression were used for the demographics to establish their relationship, if any, to the findings. ^ Key findings of the study were that reliable and valid estimates can be developed for the instrument. The multiple regression analysis for model 1 and 2 accounted for a variance of 3% and 5% for self-perceptions of global awareness (factor 1). The regression model also accounted for a 5% and 13% variance in the two models for attitudes toward global social issues (factor 2). The demographics that were statistically significant were: ethnicity, gender, SES, parents’ education, listening to music, getting the news, speaking a second language, GPA, classes taken in the social sciences, and visiting other countries. An important finding for the study was those attending public schools (as opposed to private schools) had more positive attitudes towards global social issues (factor 2) The statistics indicated that these students had taken history, economics, and social studies – a curriculum infused with global perspectives.^

Through wafer 3D Vertical Micro-Coaxial Probe for high frequency material characterization and millimeter wave packaging systems

This work presents the development of an in-plane vertical micro-coaxial probe using bulk micromachining technique for high frequency material characterization. The coaxial probe was fabricated in a silicon substrate by standard photolithography and a deep reactive ion etching (DRIE) technique. The through-hole structure in the form of a coaxial probe was etched and metalized with a diluted silver paste. A co-planar waveguide configuration was integrated with the design to characterize the probe. The electrical and RF characteristics of the coaxial probe were determined by simulating the probe design in Ansoft's High Frequency Structure Simulator (HFSS). The reflection coefficient and transducer gain performance of the probe was measured up to 65 GHz using a vector network analyzer (VNA). The probe demonstrated excellent results over a wide frequency band, indicating its ability to integrate with millimeter wave packaging systems as well as characterize unknown materials at high frequencies. The probe was then placed in contact with 3 materials where their unknown permittivities were determined. To accomplish this, the coaxial probe was placed in contact with the material under test and electromagnetic waves were directed to the surface using the VNA, where its reflection coefficient was then determined over a wide frequency band from dc-to -65GHz. Next, the permittivity of each material was deduced from its measured reflection coefficients using a cross ratio invariance coding technique. The permittivity results obtained when measuring the reflection coefficient data were compared to simulated permittivity results and agreed well. These results validate the use of the micro-coaxial probe to characterize the permittivity of unknown materials at high frequencies up to 65GHz.

Enhancing non-refractory aerosol apportionment from an urban industrial site through receptor modelling of complete high time-resolution aerosol mass spectra

Receptor modelling was performed on quadrupole unit mass resolution aerosol mass spectrometer (Q-AMS) sub-micron particulate matter (PM) chemical speciation measurements from Windsor, Ontario, an industrial city situated across the Detroit River from Detroit, Michigan. Aerosol and trace gas measurements were collected on board Environment Canada’s CRUISER mobile laboratory. Positive matrix factorization (PMF) was performed on the AMS full particle-phase mass spectrum (PMFFull MS) encompassing both organic and inorganic components. This approach was compared to the more common method of analysing only the organic mass spectra (PMFOrg MS). PMF of the full mass spectrum revealed that variability in the non-refractory sub-micron aerosol concentration and composition was best explained by six factors: an amine-containing factor (Amine); an ammonium sulphate and oxygenated organic aerosol containing factor (Sulphate-OA); an ammonium nitrate and oxygenated organic aerosol containing factor (Nitrate-OA); an ammonium chloride containing factor (Chloride); a hydrocarbon like organic aerosol (HOA) factor; and a moderately oxygenated organic aerosol factor (OOA). PMF of the organic mass spectrum revealed three factors of similar composition to some of those revealed through PMFFull MS: Amine, HOA and OOA. Including both the inorganic and organic mass proved to be a beneficial approach to analysing the unit mass resolution AMS data for several reasons. First, it provided a method for potentially calculating more accurate sub-micron PM mass concentrations, particularly when unusual factors are present, in this case, an Amine factor. As this method does not rely on a priori knowledge of chemical species, it circumvents the need for any adjustments to the traditional AMS species fragmentation patterns to account for atypical species, and can thus lead to more complete factor profiles. It is expected that this method would be even more useful for HR-ToF-AMS data, due to the ability to better understand the chemical nature of atypical factors from high resolution mass spectra. Second, utilizing PMF to extract factors containing inorganic species allowed for the determination of extent of neutralization, which could have implications for aerosol parameterization. Third, subtler differences in organic aerosol components were resolved through the incorporation of inorganic mass into the PMF matrix. The additional temporal features provided by the inorganic aerosol components allowed for the resolution of more types of oxygenated organic aerosol than could be reliably re-solved from PMF of organics alone. Comparison of findings from the PMFFull MS and PMFOrg MS methods showed that for the Windsor airshed, the PMFFull MS method enabled additional conclusions to be drawn in terms of aerosol sources and chemical processes. While performing PMFOrg MS can provide important distinctions between types of organic aerosol, it is shown that including inorganic species in the PMF analysis can permit further apportionment of organics for unit mass resolution AMS mass spectra.

Identifying the Structure and Fate of Wastewater Derived Organic Micropollutants by High-resolution Mass Spectrometry

Human activities represent a significant burden on the global water cycle, with large and increasing demands placed on limited water resources by manufacturing, energy production and domestic water use. In addition to changing the quantity of available water resources, human activities lead to changes in water quality by introducing a large and often poorly-characterized array of chemical pollutants, which may negatively impact biodiversity in aquatic ecosystems, leading to impairment of valuable ecosystem functions and services. Domestic and industrial wastewaters represent a significant source of pollution to the aquatic environment due to inadequate or incomplete removal of chemicals introduced into waters by human activities. Currently, incomplete chemical characterization of treated wastewaters limits comprehensive risk assessment of this ubiquitous impact to water. In particular, a significant fraction of the organic chemical composition of treated industrial and domestic wastewaters remains uncharacterized at the molecular level. Efforts aimed at reducing the impacts of water pollution on aquatic ecosystems critically require knowledge of the composition of wastewaters to develop interventions capable of protecting our precious natural water resources.

The goal of this dissertation was to develop a robust, extensible and high-throughput framework for the comprehensive characterization of organic micropollutants in wastewaters by high-resolution accurate-mass mass spectrometry. High-resolution mass spectrometry provides the most powerful analytical technique available for assessing the occurrence and fate of organic pollutants in the water cycle. However, significant limitations in data processing, analysis and interpretation have limited this technique in achieving comprehensive characterization of organic pollutants occurring in natural and built environments. My work aimed to address these challenges by development of automated workflows for the structural characterization of organic pollutants in wastewater and wastewater impacted environments by high-resolution mass spectrometry, and to apply these methods in combination with novel data handling routines to conduct detailed fate studies of wastewater-derived organic micropollutants in the aquatic environment.

In Chapter 2, chemoinformatic tools were implemented along with novel non-targeted mass spectrometric analytical methods to characterize, map, and explore an environmentally-relevant “chemical space” in municipal wastewater. This was accomplished by characterizing the molecular composition of known wastewater-derived organic pollutants and substances that are prioritized as potential wastewater contaminants, using these databases to evaluate the pollutant-likeness of structures postulated for unknown organic compounds that I detected in wastewater extracts using high-resolution mass spectrometry approaches. Results showed that application of multiple computational mass spectrometric tools to structural elucidation of unknown organic pollutants arising in wastewaters improved the efficiency and veracity of screening approaches based on high-resolution mass spectrometry. Furthermore, structural similarity searching was essential for prioritizing substances sharing structural features with known organic pollutants or industrial and consumer chemicals that could enter the environment through use or disposal.

I then applied this comprehensive methodological and computational non-targeted analysis workflow to micropollutant fate analysis in domestic wastewaters (Chapter 3), surface waters impacted by water reuse activities (Chapter 4) and effluents of wastewater treatment facilities receiving wastewater from oil and gas extraction activities (Chapter 5). In Chapter 3, I showed that application of chemometric tools aided in the prioritization of non-targeted compounds arising at various stages of conventional wastewater treatment by partitioning high dimensional data into rational chemical categories based on knowledge of organic chemical fate processes, resulting in the classification of organic micropollutants based on their occurrence and/or removal during treatment. Similarly, in Chapter 4, high-resolution sampling and broad-spectrum targeted and non-targeted chemical analysis were applied to assess the occurrence and fate of organic micropollutants in a water reuse application, wherein reclaimed wastewater was applied for irrigation of turf grass. Results showed that organic micropollutant composition of surface waters receiving runoff from wastewater irrigated areas appeared to be minimally impacted by wastewater-derived organic micropollutants. Finally, Chapter 5 presents results of the comprehensive organic chemical composition of oil and gas wastewaters treated for surface water discharge. Concurrent analysis of effluent samples by complementary, broad-spectrum analytical techniques, revealed that low-levels of hydrophobic organic contaminants, but elevated concentrations of polymeric surfactants, which may effect the fate and analysis of contaminants of concern in oil and gas wastewaters.

Taken together, my work represents significant progress in the characterization of polar organic chemical pollutants associated with wastewater-impacted environments by high-resolution mass spectrometry. Application of these comprehensive methods to examine micropollutant fate processes in wastewater treatment systems, water reuse environments, and water applications in oil/gas exploration yielded new insights into the factors that influence transport, transformation, and persistence of organic micropollutants in these systems across an unprecedented breadth of chemical space.

Screening for Sexual Trauma, Intimate Partner Violence and Mental Health Symptoms among HIV Positive South African Women

Background: The psychological sequelae of sexual trauma and physical intimate partner violence (IPV) exposure can lead to poor HIV care outcomes, including poor treatment adherence. This study aimed to estimate the prevalence of and factors associated with mental health symptoms and trauma among HIV positive women. Additionally, the study aimed to assess the feasibility and acceptability of screening for trauma and mental health symptoms among HIV positive South African women. Finally, the study aimed to elicit healthcare workers’ perceptions related to sexual trauma and the provision of care and services for HIV positive women with trauma histories.

Methods: The study utilized a mixed-methods approach that included a cross-sectional survey of 70 HIV positive women recruited through referral sampling and key informant interviews with seven healthcare workers (HCWs). A study-screening instrument consisting of 24 items from standard measures was used to screen women for sexual trauma, physical intimate partner violence (IPV), depression and PTSD. Sexual trauma and IPV were assessed across the lifetime, while depression and PTSD were current assessments. Logistic regression models were used to explore the relationship between trauma exposure and mental health symptoms, while controlling for age and education. Interview transcripts were coded and analyzed for emergent themes on HCWs perceptions on sexual trauma and HIV care.

Results: Among participants, 51% had sexual trauma experience and 75% had intimate partner violence (IPV) experience. Among participants, 36% met screening criteria for major depression; among those with traumatic experiences (n=57), 70% met screening criteria for post-traumatic stress disorder (PTSD). Compared to having no sexual trauma or IPV exposure, having both sexual trauma and IPV was significantly associated with higher odds of depression (OR = 8.11; 95% CI 1.48-44.34), while having either IPV or sexual trauma individually was not significantly associated with increased odds of depression. Compared to having either IPV or sexual trauma, having both sexual trauma and IPV was not significantly associated with PTSD. Responses from participants’ feedback on screening process suggest that screening was feasible and acceptable to participants. Some of the health care workers (HCWs) did not perceive dealing with trauma to be part of their duties, but instead viewed social workers or psychologists as the appropriate health cadre to provide care related to trauma and mental health.

Conclusions: High levels of sexual trauma, IPV and mental health distress were reported among HIV positive women in this setting. Screening for trauma and mental health symptoms was acceptable to the participants, but several challenges were encountered in implementing screening. Given the potential impact of trauma and mental health on HIV care engagement, interventions to address trauma and its psychological sequelae are needed.

Characterizing Genetic Drivers of Lymphoma through High-Throughput Sequencing

The advent of next-generation sequencing, now nearing a decade in age, has enabled, among other capabilities, measurement of genome-wide sequence features at unprecedented scale and resolution.

In this dissertation, I describe work to understand the genetic underpinnings of non-Hodgkin’s lymphoma through exploration of the epigenetics of its cell of origin, initial characterization and interpretation of driver mutations, and finally, a larger-scale, population-level study that incorporates mutation interpretation with clinical outcome.

In the first research chapter, I describe genomic characteristics of lymphomas through the lens of their cells of origin. Just as many other cancers, such as breast cancer or lung cancer, are categorized based on their cell of origin, lymphoma subtypes can be examined through the context of their normal B Cells of origin, Naïve, Germinal Center, and post-Germinal Center. By applying integrative analysis of the epigenetics of normal B Cells of origin through chromatin-immunoprecipitation sequencing, we find that differences in normal B Cell subtypes are reflected in the mutational landscapes of the cancers that arise from them, namely Mantle Cell, Burkitt, and Diffuse Large B-Cell Lymphoma.

In the next research chapter, I describe our first endeavor into understanding the genetic heterogeneity of Diffuse Large B Cell Lymphoma, the most common form of non-Hodgkin’s lymphoma, which affects 100,000 patients in the world. Through whole-genome sequencing of 1 case as well as whole-exome sequencing of 94 cases, we characterize the most recurrent genetic features of DLBCL and lay the groundwork for a larger study.

In the last research chapter, I describe work to characterize and interpret the whole exomes of 1001 cases of DLBCL in the largest single-cancer study to date. This highly-powered study enabled sub-gene, gene-level, and gene-network level understanding of driver mutations within DLBCL. Moreover, matched genomic and clinical data enabled the connection of these driver mutations to clinical features such as treatment response or overall survival. As sequencing costs continue to drop, whole-exome sequencing will become a routine clinical assay, and another diagnostic dimension in addition to existing methods such as histology. However, to unlock the full utility of sequencing data, we must be able to interpret it. This study undertakes a first step in developing the understanding necessary to uncover the genomic signals of DLBCL hidden within its exomes. However, beyond the scope of this one disease, the experimental and analytical methods can be readily applied to other cancer sequencing studies.

Thus, this dissertation leverages next-generation sequencing analysis to understand the genetic underpinnings of lymphoma, both by examining its normal cells of origin as well as through a large-scale study to sensitively identify recurrently mutated genes and their relationship to clinical outcome.

Report on the High Quality Jobs Program (HQJP) and the Grow Iowa Values Fund (GIVF), administered by the Iowa Economic Development Authority (IEDA), previously known as the Department of Economic Development, for the period July 1, 2003 through June 30, 2014

Report on the High Quality Jobs Program (HQJP) and the Grow Iowa Values Fund (GIVF), administered by the Iowa Economic Development Authority (IEDA), previously known as the Department of Economic Development, for the period July 1, 2003 through June 30, 2014

Fetal Alcohol Spectrum Disorder Primary Prevention through FASD Diagnosis: Identification of High-Risk Birth Mothers through the Diagnosis of their Children. Follow-up Study

Thesis (Master's)--University of Washington, 2016-08