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AMMONIA BIOMANUFACTURING WITH ENGINEERED PHOTOSYNTHETIC BACTERIA
Get PDFAmmonia production is one of the most important industries in the world while the current method of ammonia manufacturing based on Haber-Bosch process is energy and carbon intense. To avoid increase amount of energy consumption and carbon emission over time, research has been conducted to optimize the current manufacturing process or discover an alternative way in ammonia production. One of the alternative methods is to use biological nitrogen fixation (BNF) process via bacteria. The BNF process utilizes nitrogen in the atmosphere, protons in the aqueous solution and electrons generated by bacteria to form free ammonia. By growing bacteria inside an electrochemical cell, the BNF process can be part of the electrochemical reaction by providing or accepting electrons. In this research, Rhodopseudomonas palustris were grown in anode side of an H shaped electrochemical cell to provide electrons for the reaction. Furthermore, genetic modification was applied to the R. palustris to increase the production of ammonia. This research revealed the growth profile of 2 R. palustris strains: CGA009 and a mutant derived from it CGA676 and their interaction with the electrochemical cell. By applying 0.1 V potential, CGA009 produced 55 % higher cell density at day 6 than the one without potential. Consequently, the nitrogen fixed as cell biomass was 54 % higher due to the modified redox environment near the electrodes compared to the controls. The research also verified that the plasmid pBBR1MCS-2 is capable of transforming genes into R. palustris and successfully expressed by using a GFP gene inserted to the plasmid backbone. This is an indication that any further molecular biological work can be done with the pBBR1MCS-2 backbone
Supports and Barriers to Extracurricular Experiential Learning Participation in Higher Education Arts Institutions
No full textHigher education arts programs are implementing experiential learning programs to address skills gaps and better prepare students for careers in an evolving arts industry. However, there is a dearth of research relating to experiential learning in the arts. As a starting point, this research explores the supports and barriers that contribute to student participation in extracurricular experiential learning programs. Chapter 1 establishes the importance of experiential learning in arts higher education and reviews existing literature to identify relevant factors that may impact student participation in extracurricular opportunities offered by higher education programs. Building on a complex web of factors identified in the literature review, Chapter 2 details an exploratory mixed methods study implemented at a higher education arts institution, with emphasis on qualitative methods to gain a more thorough understanding of student experiences specific to arts conservatory settings. To further explore this area of research, Chapter 3 outlines rationale for developing the Experiential Learning Participation Survey, a multi-method survey that higher education arts institutions can utilize to better understand their own unique audiences and settings moving forward. Drawing on the findings of the mixed methods study, this chapter also discusses the process for designing and validating the survey. Finally, Chapter 4 describes the initial implementation of the Experiential Learning Participation Survey, as well as preliminary validation results, data analysis, and findings. Ultimately, this research establishes a foundational understanding of arts students’ interactions with extracurricular experiential learning programs, supports and barriers to participation, and students’ perspective on relevance of experiential learning to their career goals, and the survey provides an accessible avenue for further research to continue to benefit evidence-based practice in this area
ASSOCIATION BETWEEN DUAL SENSORY LOSS AND DEMENTIA AND MILD COGNITIVE IMPAIRMENT IN OLDER ADULTS
Get PDFBackground
Dual sensory loss (DSL) is associated with dementia in existing studies based on measures of either self-reported or limited racial diversity populations. Current analysis based on objective measures are needed for public health research field.
Methods
We adopted data from Eye Determinants of Cognition (EyeDOC study), an ancillary study in the Atherosclerosis Risk in Communities – Neurocognitive study (ARIC-NCS). Analytic sample incorporate 927 participants (aged 71-93 years, 63% female, 44% self-reported Black race) from Jackson, Mississippi and Washington Country, Maryland at visit 6 (2017-2019) with complete outcome, exposure, and covariate data. DSL was defined as presence of hearing loss (PTA > 25 dB HL in the better-hearing ear) and vision loss (presenting visual acuity worse than 20/40 in the better-seeing eye). DSL was then modeled as a four-category exposure variable in analysis: no hearing and no vision loss (reference group), hearing loss only, vision loss only, and both hearing and vision loss (DSL).
Results
In the study sample of 927 participants, overall, the mean age was 78.7 years, with a range of 71- 93 years. 63% were female and 44% self-reported Black race. In the multivariable-adjusted analysis, compared to participants with no sensory loss, participants with DSL had a significant higher prevalence of dementia/MCI (PR=2.23, 95% CI: 1.39, 3.58). This estimate attenuated (PR=2.04, 95% CI: 1.24, 3.34) after adjusting for depressive symptoms.
Conclusion
DSL was associated with a significant increased prevalence of dementia, but individual sensory losses (hearing or vision only) were not statistically significant associated with the prevalence of dementia/MCI. These findings highlight the potential benefit of addressing sensory loss comprehensively, and whether combing vision and hearing interventions could yield a greater reduction in cognitive decline/dementia. Further research should address combined treatment for both hearing and vision loss to protect brain health
A LOW-VOLUME, HIGH-THROUGHPUT APPROACH TO ENABLE EARLY STABILITY SCREENING OF MONOCLONAL ANTIBODY THERAPEUTICS
No full textMonoclonal antibodies (mAbs) are increasingly being developed to treat a range of human ailments, including cancers, inflammatory conditions, and infectious diseases. However, their progress in the pharmaceutical space is ultimately constrained by efficacy, developability, and cost. Arising from advancements in modern computing and machine learning (ML), in silico characterization is emerging as powerful tool to rapidly screen and identify more efficacious, developable mAbs. Though these tools exist, training ML models requires a substantial pool of balanced, unbiased data. Data for early-stage developability assessment is especially difficult to collect at the required scale due to the constraining time and material requirements of conventional in vitro biophysical characterization assays. Gravitation towards higher concentration formulations supporting subcutaneous administration further increases these time and material requirements. As a result, there is an urgent need for low-volume (LV), high-throughput (HT) adaptations of conventional biophysical characterization assays which can support studies of high concentration mAb formulations.
This study focuses on developing an LV HT accelerated stability (AS) approach to measure degradation—and, therefore, forecast shelf-life—for early-stage screening at the scale required to enable in silico developability prediction. We developed an automation-amenable approach built upon a standard 384-well plate platform that requires 92% less material than the gold-standard 2R vial approach. We demonstrated that the LV HT AS approach provides degradation results via HP-SEC within 0.05% per month of the gold-standard after 4-weeks at 40 °C and 75% relative humidity. We anticipate next steps to test its robustness and further optimize the approach
ENHANCED ALGORITHMS TO DETECT AND CHARACTERIZE CONSERVED REGULATORY SEQUENCES
Get PDFMutations in gene regulatory elements are associated with increased risk for many complex genetic diseases such as schizophrenia, diabetes, and cancer. However, the degenerate sequence structures of regulatory elements and their complex contribution to gene expression pose great challenges to understanding pathogenesis induced by regulatory mutations. To decipher the regulatory genome, advancement in both experimental and computational methods to characterize gene regulatory elements is indispensable. This dissertation details my contribution to this effort, with emphasis on the computational aspect.
First, I collaborated with members of the ENCODE and IGVF consortia to functionally characterize diverse gene regulatory elements through systematic epigenetic perturbation with CRISPRi. For example, we screened putative enhancers of core transcription factors that drive differentiation of embryonic stem cells to definitive endoderm (e.g., SOX17, GATA6), and discovered that enhancers modulate the speed of cell differentiation through enhancer strength and redundancy. Further, we quantitatively analyzed diverse CRISPR screen methodologies, and identified important principles of non-coding CRISPR screens that will streamline future efforts for enhancer functional characterization.
Second, to facilitate functional characterization of regulatory elements through model species, we developed a novel genome alignment algorithm designed to identify conserved distal enhancers. Biological functions and variant impacts of human enhancers are often tested using their conserved orthologous counterparts in model species such as mice. However, due to both rapid evolution of enhancers and computational limitations, mapping conserved distal enhancers between distant mammals remains a challenge. To improve upon existing computational methods, we developed a novel genome alignment algorithm using gapped-kmer sequence features, which have previously been shown to effectively model regulatory sequences. We comprehensively evaluated the novel algorithm, gkm-align, using thousands of DNase-seq data generated from diverse human and mouse cell/tissues. Through this expansive dataset, we observed intriguingly high level of variation in enhancer conservation across distinct cell/tissues, which is explainable through association with transposable elements. This observation provides a quantitative support to the notion that enhancer evolution and transcriptional rewiring may be driven by transposable elements that carry human transcription factor binding sequences. We show that while cell-specific regulatory vocabulary is conserved, enhancers evolve more rapidly than other genomic elements such as promoters and CTCF binding sites. In spite of the rapid evolution, gkm-align discovers more than 20,000 novel enhancers with conserved epigenetic profiles, missed by standard alignment methods
The Role of BCL-12 in Sensitizing BAX and BAK Induced Mammalian Cell Death
No full textApoptosis, a vital process that regulates tissue homeostasis, is a well characterized programmed cell death pathway that is governed by a sophisticated interplay between regulatory proteins of the BCL-2 family. There are three main groups of interacting proteins that regulate apoptosis, the anti-death BCL-2 family proteins (BCL-2, BCL-xL), the pro-death BCL-2 homologs (BAX, BAK), and a separate more heterogeneous group of BH3-only proteins (BIM, BID and others). This thesis project investigated an understudied, more distantly related BCL-2 family member known as BCL-12 (also referred as BCL2L12) using biochemical and fluorescence microscopy approaches. The results suggest that BCL-12 regulates the anti-apoptotic function of BCL-xL based on transient transfection studies in HeLa cells. Also described are preliminary studies examining the effects of BCL-12 mutants on BAK-induced cell death, suggesting the interesting possibility that BCL-12 may influence BAX and BAK differently in the presence of BCL-xL
How Emerging Automation Tools Will Reorient Research Administration
Get PDFOver the coming years, Automation tools promise to revolutionize Research Administration by enhancing efficiency, accuracy and strategic decision-making. This desk research project explores how emerging Automation tools such as Artificial Intelligence (AI), Machine Learning (ML) and Robotic Process Automation (RPA) will streamline routine administrative processes, reduce manual workloads and improve compliance and data integrity. This project examines current literature to identify key areas where Automation tools have been successfully implemented, including in life science research laboratories, grants management in universities, funding decisions from donations to Nonprofit Organizations (NPOs), and policy and decision-making in for-profit companies. Increased Automation will redirect Research Administrators to gravitate toward activities such as strategic planning and stakeholder engagement. In addition, the integration of Automation tools can lead to significant cost savings and resource optimization. The findings indicate that a strategic adoption of Automation in Research Administration is crucial for enhancing operational efficiency, ensuring compliance and maintaining competitive advantage in the rapidly evolving research landscape. This project concludes with recommendations for Research Entities to implement certain changes, and prospective and current Research Administrators to develop certain skill sets, that will be useful in the increased-Automation workplace
INVESTIGATING THE ROLE OF THE GPI-ANCHOR CLEAVING ENZYME GDE2 IN NEURODEGENERATION
Get PDFAlzheimer’s disease (AD) and related dementias (ADRDs) such as Amyotrophic lateral sclerosis-Frontotemporal dementia (ALS-FTD) are the leading causes of dementia, affecting the lives of millions of people each year. Despite being a widespread public health concern, knowledge of the etiology of neurodegenerative pathologies in ADRDs is limited and has hindered the development of effective treatments. Glycerophosphodiester phosphodiesterase 2 (GDE2) is a six-transmembrane protein which cleaves the glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the outer leaflet of the plasma membrane. GDE2 has important roles in neurogenesis and oligodendrocyte maturation during development. It is emerging that GDE2 also has distinct postdevelopmental functions in the nervous system. Recent studies have shown that postnatal expression of GDE2 is required for neuronal survival in the mammalian spinal cord and for the non-amyloidogenic processing of amyloid precursor protein (APP). GDE2 ablation in mice causes spinal motor neuron degeneration and increased amyloidogenic APP processing leading to increased toxic amyloid-beta (Aβ) production in the brain. Interestingly, these phenotypes are characteristic of Amyotrophic lateral sclerosis (ALS) and AD respectively. Indeed, GDE2 accumulates intracellularly and is hypofunctional in AD patient brains, suggesting that GDE2 loss of function may contribute to Aβ pathology in AD.
In this study we find that GDE2 also accumulates in intracellular compartments in the brains of ALS and ALS-FTD patients and this correlates with reduced release of GPI-anchored proteins in ALS patient cerebrospinal fluid. We also show that GDE2 loss contributes to multiple cellular, molecular, and behavioral pathologies associated with ADRDs, including nuclear pore complex injury, nucleocytoplasmic transport defects, and TDP-43 mislocalization and loss. These findings provide insight into the mechanisms underlying ADRD pathogenesis and highlight GDE2 as a potentially important therapeutic target for disease modifying therapies
VAPOR PHASE DEPOSITION OF ZINC-IMIDAZOLATE THIN FILMS FOR LITHOGRAPHY RESISTS AND GAS SEPARATION MEMBRANES
Get PDFMetal-organic frameworks (MOFs) are a type of crystalline materials that were first synthesized in the 1990s that consist of nodes consisting of metal containing clusters or individual metals bridged by organic linkers and have with pores in the size range (~0.1 – 1.0 nm) of many small molecules. Since their initial synthesis, thousands of different MOFs have been synthesized, with the crystal structures of over 10,000 different MOFs having been deposited in the Cambridge Crystallographic Data Centre. Their pore sizes, combined with a tunable chemical functionality, has led to an incredible amount of research focus and thousands of MOF-related research articles focused in the past decade. Their potential for usage in microelectronics and as separation agents has yet to be realized commercially and is a major focus of this dissertation.
Chemical separations account for 1/6th of world energy use, with distillation alone accounting for half of that. Membranes can provide more efficient separations because they rely on pressure gradients, rather than phase changes, to drive separations. This work discusses the solvent-free fabrication of MOF-based membranes using zeolitic imidazolate frameworks (ZIFs) as the selective layer with permeances and selectivities greater than 1 x 10-7 mol/(m2 s Pa) and 50, respectively.
The microelectronics industry is driven by the desire to decrease the size of microelectronic circuits, with Moore’s law describing the general trend of the doubling of transistor density on computer chips every two years. In the last 50 years, the smallest dimensions of these circuits have been reduced from the width of a hair to less than 100 atoms. This work discusses the vapor phase deposition and development of ZIF-based patterneable photoresist materials with a pitch as small as 30 nm.
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The research to be described here relies heavily on atomic layer deposition (ALD), which ALD relies on sequential self-terminating surface reactions and allows for atomic scale control over film thickness. We developed and characterized a process described here for the deposition of amorphous zinc-imidazolate (aZnMIm) thin films that are chemically similar to ZIF-8 and can be used as high-resolution photolithography resists and as a precursor layer for ZIF-8 membranes
Behavioral health services for co-occurring mental health and substance use disorders under the Affordable Care Act
Get PDFBackground: Few adults with co-occurring mental and substance use disorders receive concurrent treatment for their mental and substance use disorders, often due to financial barriers. The goal of this dissertation was to examine how Medicaid expansion impacted: 1) concurrent service availability, 2) concurrent treatment-seeking settings, and 3) subgroups of adults continuing to not perceive a need for substance use treatment.
Methods: Facility-level data came from the 2010, 2012, and 2014 – 2019 National Mental Health Services Survey (N-MHSS) and 2008 – 2019 National Survey of Substance Abuse Treatment Services (N-SSATS) for Aim 1 and individual-level data came from the 2009 – 2018 National Survey on Drug Use and Health (NSDUH) for Aims 2 and 3. In Aim 1, I used trial emulation with difference-in-difference to identify if expansion affected co-located facility growth. In Aims 2a and 2b, I used weighted logistic regression with propensity scores to examine if expansion affected concurrent treatment and its setting. In Aims 2c and 3, I sued confirmatory latent class analysis to identify if expansion changed subgroups of adults seeking concurrent treatment in formal settings and who did not perceive a need for substance use treatment, respectively.
Results: Co-located facility growth did not differ between expansion and non-expansion states, and was slower in expansion states two to four years after expansion. Compared to adults with concurrent disorders before expansion, those after expansion were no more or less likely to seek concurrent treatment nor receive concurrent treatment in formal settings over a mix of formal and informal settings. Further, expansion did not change the subgroups of adults who sought concurrent treatment in formal settings, although a new small subgroup marked by heroin use disorder may have emerged. Last, subgroups of adults with no perceived need for substance use treatment may have changed after expansion.
Conclusion: The results of analyses suggest that Medicaid expansion did not improve concurrent treatment access and use for adults with co-occurring mental and substance use disorders. However, expansion may have given adults with heroin use disorder access to concurrent treatment in formal settings