Neurodevelopmental Consequences of Prenatal Alcohol Exposure: Behavioural and Transcriptomic Alterations in a Mouse Model

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term referring to a range of physical, behavioural, and cognitive deficits resulting from prenatal alcohol exposure. The resulting abnormalities are heterogeneous and often attributed to timing and dosage of alcohol exposure. However, the specific effects of developmental timing are not well-known. This research used C57BL/6J (B6) as an animal model for early (human trimester one) and mid-gestation (human trimester two) alcohol exposure. Pregnant B6 mice were injected with 2.5 g/kg ethanol on gestational day (GD) 8 and 11 (trimester one equivalent), or on GD 14 and 16 (trimester two equivalent). Resulting pups were followed from birth to adulthood using FASD-relevant behavioural tests. At postnatal day (PD) 70, whole brain tissues were extracted. A third group of dams were injected on GD 16 (short-term). Two hours post injection, fetal brains were removed. Brains were used for genome-wide expression analysis, including microRNAs. Downstream analyses were completed using software packages and online databases. All ethanol-treated pups showed motor skill delays, increased activity, and spatial learning deficits. Gene expression analysis resulted in altered expression of 48 short-term genes between ethanol and control mice treated during the second trimester. Fifty-five and 68 genes were differentially-expressed in the long-term analyses of mice treated during trimester one and two, respectively. Genes involved in immune system response were disrupted across all treatments. Disrupted short-term processes included cytoskeleton development and immunological functions. Processes altered in long-term exposures included stress signaling, DNA stability, and cellular proliferation. MicroRNA analyses returned eight and 20 differentially-expressed miRNAs in trimesters one and two, respectively. Target filtering of trimester one microRNAs and mRNAs resulted in inverse relationships between miR-532-5p and Atf1, Itpripl2, and Stxbp6. Trimester two target filtering resulted in miR-302c targeting Ccdc6. Gene expression and microRNA results demonstrate the stage-specific genes and processes altered during neurodevelopment upon ethanol exposure. Certain cellular processes are disrupted no matter the timing of ethanol exposure. Given that microRNAs are fine-tuners of gene expression, they may play an important role in the maintenance of FASD. Furthermore, transcriptomic changes in the brain may explain the observed behavioural effects of prenatal ethanol exposure

Internship Portfolio

My one-year internship program work was with Mayo Clinic, Rochester. I was involved in the software development as part of a work term, all of which will be outlined in this report. The report will cover some background information on the projects I was involved in, as well as details on how the projects were developed. The report also states how and what academic courses and projects helped me in overall internship experience so far. At the beginning of the internship, I formulated serval learning goals, which I wanted to achieve: To understand the functioning and working conditions of the organization; To explore working in a professional environment; To explore the work environment for the possibility of a future career; To utilize my gained skills and knowledge; To find skills and knowledge I still need to work in a professional environment; To learn about software development life cycle; To learn about the development methodologies; To obtain fieldwork experience/collect data in an environment unknown for me; To obtain experience working in multicultural and diverse environment; To enhance my interpersonal and technical skills; To network with professionals in the industry. There are five major projects that I had a significant role in. The first project was Space Tools, involved gaining a good understanding of a javascript framework called Angular. My task was to study its working, develop wireframes from the view point of developing an application using that technology. My task was to Understand working with Angular framework, Understand working with Git, Develop wireframes. As this was my first project with Mayo Clinic, particularly at Development Shared Services (DSS) as a team project, I also had a large scope of understanding Agile Methodology - Scrum Process in particular. The second project was BAMS which was a rewrite of existing application in Windows Presentation Framework(WPF) and .Net backend. In this project my tasks were Understand using WinForms and WPF, Develop pages using WPF- MVVM Framework. The third project was DSA, where I acquired knowledge of working on Angular4 and frontend Unit testing in Karma using Mocha and Chai frameworks. The fourth project is MML Notification and Delivery, which started with an analysis phase in which were asked to analyze the data flow and system integrations the current Mayo Access and Mayo Link (MML Internal Operations) are dependent upon. We are to provide a new functionality to Mayo Access users of Notification and Delivery of tests results. The current project that I’m working on now is “MML Database Analysis”. This project is in the analysis phase. We were given a task to analyze MML databases to write an API instead of frontend calls to the database. I acquired many new technical skills throughout my work. I acquired new knowledge in Front-end development using various versions of Angular framework and Unit testing using Mocha and Chai framework in Karma. I also brushed my HTML/HTML5, CSS/CSS3, Javascript, Java, C# skills while working on various projects. Then I was introduced to the area of research and analysis and how to approach it. Most importantly, the work included good fellowship, cooperative teamwork and accepting responsibilities. Although I spent much time as a learning curve, I found that I was well trained in certain areas that helped me substantially in my projects. Many programming skills and Software Development Life Cycle understanding that I used in my internship, such as programming style and design, were the skills that I had acquired during my studies in Computer Science. This report also includes advantages of using Angular framework over other Javascript frameworks. The report concludes with my overall impressions of my work experience as well as my opinion of the Industrial Internship Program in general

Navigation, Path Planning, and Task Allocation Framework For Mobile Co-Robotic Service Applications in Indoor Building Environments

Recent advances in computing and robotics offer significant potential for improved autonomy in the operation and utilization of today’s buildings. Examples of such building environment functions that could be improved through automation include: a) building performance monitoring for real-time system control and long-term asset management; and b) assisted indoor navigation for improved accessibility and wayfinding. To enable such autonomy, algorithms related to task allocation, path planning, and navigation are required as fundamental technical capabilities. Existing algorithms in these domains have primarily been developed for outdoor environments. However, key technical challenges that prevent the adoption of such algorithms to indoor environments include: a) the inability of the widely adopted outdoor positioning method (Global Positioning System - GPS) to work indoors; and b) the incompleteness of graph networks formed based on indoor environments due to physical access constraints not encountered outdoors. The objective of this dissertation is to develop general and scalable task allocation, path planning, and navigation algorithms for indoor mobile co-robots that are immune to the aforementioned challenges. The primary contributions of this research are: a) route planning and task allocation algorithms for centrally-located mobile co-robots charged with spatiotemporal tasks in arbitrary built environments; b) path planning algorithms that take preferential and pragmatic constraints (e.g., wheelchair ramps) into consideration to determine optimal accessible paths in building environments; and c) navigation and drift correction algorithms for autonomous mobile robotic data collection in buildings. The developed methods and the resulting computational framework have been validated through several simulated experiments and physical deployments in real building environments. Specifically, a scenario analysis is conducted to compare the performance of existing outdoor methods with the developed approach for indoor multi-robotic task allocation and route planning. A simulated case study is performed along with a pilot experiment in an indoor built environment to test the efficiency of the path planning algorithm and the performance of the assisted navigation interface developed considering people with physical disabilities (i.e., wheelchair users) as building occupants and visitors. Furthermore, a case study is performed to demonstrate the informed retrofit decision-making process with the help of data collected by an intelligent multi-sensor fused robot that is subsequently used in an EnergyPlus simulation. The results demonstrate the feasibility of the proposed methods in a range of applications involving constraints on both the environment (e.g., path obstructions) and robot capabilities (e.g., maximum travel distance on a single charge). By focusing on the technical capabilities required for safe and efficient indoor robot operation, this dissertation contributes to the fundamental science that will make mobile co-robots ubiquitous in building environments in the near future.PHDCivil EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/143969/1/baddu_1.pd

Attachment Issues: Assessing the Relationship Between Newcomers and the Constitution

Are you attached to the principles of the U.S. Constitution? How do you prove it—do you feel it, or just know it? What role does it play in your daily life as a citizen? Ever since one of the first acts of the U.S. Congress, the Naturalization Act of 1795, applicants for citizenship have been required to demonstrate that they are “attached to the principles of the [C]onstitution of the United States.” This requirement has been at the forefront of fierce debates in U.S. constitutional history and, although it has had limited usage after WWII, it has recently been brought up again. In 2021, President Biden announced a new bill (Citizenship Act 2021) which if passed by Congress would facilitate the pathway to citizenship for 11 million undocumented migrants that would need to show attachment as part of their naturalization requirements. Attachment requirements have also mushroomed in other liberal democracies, which have had the U.S. model in mind when designing their naturalization procedures. This Article is the first to present a systematic updated legal analysis of the attachment requirement in U.S. constitutional law and citizenship policy from a comparative perspective. The Article tracks the historical roots of the attachment requirement since the American colonies to date, demonstrates the controversies and disputes over its essence, and assesses its underlying theory, purpose, content, and methods. Overall, the Article provides normative insights, comparative lessons, and historical contexts to one of the most fundamental questions of the political community—who belongs, under what conditions, and why

An extensible and scalable Pilot-MapReduce framework for data intensive applications on distributed cyberinfrastructure

The volume and complexity of data that must be analyzed in scientific applications is increasing exponentially. Often, this data is distributed; thus, the ability to analyze data by localizing it will yield limited returns. Therefore, an efficient processing of large distributed datasets is required, whilst ideally not introducing fundamentally new programming models or methods. For example, extending MapReduce - a proven effective programming model for processing large datasets, to work more effectively on distributed data and on different infrastructure (such as non-Hadoop, general-purpose clusters) is desirable. We posit that this can be achieved with an effective and efficient runtime environment and without refactoring MapReduce itself. MapReduce on distributed data requires effective distributed coordination of computation (map and reduce) and data, as well as distributed data management (in particular the transfer of intermediate data units). To address these requirements, we design and implement Pilot-MapReduce (PMR) - a flexible, infrastructure-independent runtime environment for MapReduce. PMR is based on Pilot abstractions for both compute (Pilot- Jobs) and data (Pilot-Data): it utilizes Pilot-Jobs to couple the map phase computation to the nearby source data, and Pilot-Data to move intermediate data using parallel data transfers to the reduce computation phase. We analyze the effectiveness of PMR over applications with different characteristics (e. g. different volumes of intermediate and output data). Our experimental evaluations show that the Pilot abstraction for data movement across multiple clusters is promising, and can lower the execution time span of the entire MapReduce execution. We also investigate the performance of PMR with distributed data using a Word Count and a genome sequencing application over different MapReduce configurations. We find that PMR is a viable tool to support distributed NGS analytics by comparing and contrasting the PMR approach to similar capabilities of Seqal and Crossbow, two Next Generation Sequencing(NGS) Hadoop MapReduce based applications. Our experiments show that PMR provides the desired flexibility in the deployment and configuration of MapReduce runs to address specific application characteristics and achieve an optimal performance, both locally and over wide-area multiple clusters

A poultry litter marker gene correlates with pathogen and indicator bacteria deposition on, growth in and transport from poultry bedding

Poultry is one of the major contributors of inputs to U.S. environmental waters due to the large number of poultry grown per year in the U.S. and litter disposal practices. Two studies were conducted during this research: (1) to determine the temporal rate of deposition and growth or decay of microorganisms in poultry litter originating from poultry feces and (2) the release and transport of poultry litter associated microorganisms from soiled poultry litter applied as fertilizer through soil columns under simulated rainfall. First, deposition studies were conducted to evaluate the deposition rate of microorganisms on poultry bedding during the growth of poultry. The studies were designed to simultaneously evaluate the growth or decay of microorganisms after deposition on the poultry bedding (i.e., wood shavings). A secondary objective of this study was to determine if there is a correlation between the poultry litter marker gene and indicator bacteria (FIB) and pathogens during deposition. Culture and qPCR analysis revealed growth of Enterococcus, Staphylococcus and Bacteroidales in the litter for up to four weeks after deposition in feces. In contrast after deposition of E. coli on the litter, the concentrations of E. coli declined after the soiled litter was separated from the poultry. The poultry litter marker Brevibacterium sp. LA35 was found to increase in the litter over time as the birds aged, but was not observed to grow in the soiled litter after deposition with feces. The deposition study aids in our understanding of the deposition, survival and growth of microorganisms from poultry feces in and on poultry litter. The next study conducted evaluated the release and transport of pathogens (Salmonella sp.), FIB (Enterococcus, and E. coli) and MST markers (LA35 and Bacteroidales) from poultry litter under simulated rainfall events through soil columns. The transport and attenuation of microorganisms was observed through an acid washed sand column and loamy sand soil columns over 10 to 30 pore volumes of deionized water. The qPCR analysis revealed that the breakthrough of pathogens and MST markers were correlated. These soil column studies aid in our understanding of the release, transport and attenuation of pathogens from poultry litter applied as an agricultural fertilizer