Hybrid dynamical systems (HDS) are time dependent systems that have both discrete and continuous behavior, such as a bouncing ball or jumping leg. The BioRobotics Lab studies HDS in order to better understand locomotion and develop controls for robotics. As controllers are developed, they need to be tested in the hybrid dynamical system (HDS) either through simulation or implementing in physical robotics. While simulated system environments are useful in early controller development, they are unable to capture all the intricacies of a physical system. Thus, testing controllers in a physical system can provide better insights for future development. We developed a hopping robot for the purpose of easily implementing controllers through software. The hopping robot is designed to be modular and easily configured for different dynamics. Simulations of the robot were also developed so that researchers can use both simulated and physical environments. This tool will help researchers develop new controllers and could bring new insights to studying hybrid dynamical systems.

International adoption in the United States began during World War II. It was developed as a humanitarian act to aid those orphaned due to the war. Since then international adoption has remained an option for Americans looking to expand their family. The Hague Convention is an international organization aimed at uniting countries in their laws regarding international adoption policy with the intent to ensure the welfare of the child. Since its founding in 1983, the Hague Convention has influenced a total of eighty - three countries including the United States. Despite the intention of the Hague Convention and its member's international adoption still places a child's welfare at higher risk than those of domestically adopted children. International adoptees are victims of human trafficking, abuse, and untimely death. Even the Hague Convention intended to improve international adoption does not advocate countries to use international adoption as a solution to aiding their orphaned population. Permitting an international adoption is promoted as a last resort for the most vulnerable of an already targeted community. The primary intent of this paper advocates for stricter enforcement and potential temporary stall on future international adoptions within the United States. This stance is taken due to issues of lack tracking of international adoptees, the failure of enforcement of international adoption laws currently in place, and the negative impact of the overtly positive marketing of international adoptions. This work intends to bring further awareness of the systemic issues of international adoption that put a child's welfare at risk. Concerning international adoption, this is highly important due to its primarily positive reputation with the general public. This research also intends to provide a solution society may advocate for or further build upon in order to take the measures necessary to ensure the welfare of a child.

The United States presence in Africa is mostly militaristic and oil-driven, whereas China's recent foray into the continent has rattled the traditional conventions for doing business and investing on the continent. Through a series of Foreign Direct Investments, International Trade, Government Funded Contractual Projects and loans by the Chinese government, China has taken direct action to infiltrate the internal economies, politics and societies of many African nations. To frame where China lays in terms of economic investments and involvement, my research examines the current state of three African nations in which China invests. The markers within a nation include the profitability of a particular industry sector, previous political relations with China, the market size of an economy or nation, political security of a nation and geopolitical strategy. I focus on three Sub-Saharan nations in which China has previous practices or a history of investments, Tanzania, Zambia and Angola. Statistical data provided by loans or investments and first-hand accounts of events are used to support my arguments about China’s involvement in the affairs of these three nations. I discuss multiple value factors for a superpower to invest in a nation and how this influences that nation’s economy and politics. The end result takes the form of a review of China’s influence on these three nations. My study gives context and poses questions for future research on the economies and political strategy behind the investments made by world powers in African countries.

Increasingly, over the past half century, antibiotic resistant plasmids have spread to a large range of bacteria increasing the demand of new antibiotics. On average, once an antibiotic has been released into the public market, a strain that is antibiotic resistant evolves within a few years. Even though the constant production of new drugs and treatments provides some temporary solutions, a better solution would be to investigate and understand bacterial plasmid mechanisms. Through my research in the UW Biology Kerr Lab, I have been exploring how bacteria maintain plasmids that contain genes encoding for antibiotic resistance. Plasmids are extra-chromosomal pieces of DNA that require the host cell to allocate energy for their general maintenance. Prior theoretical research suggests that, to avoid this allocation of resources, the host should lose antibiotic resistant plasmids over time when the plasmid is no longer beneficial to the host’s fitness, for example when the antibiotic is no longer present. We found that many plasmids across multiple bacterial species persist in their hosts, even in the absence of selection for the plasmid. Currently, I am testing whether changing the environmental conditions experienced by the host/plasmid pairs, specifically from a nutrient-rich to minimal media, will affect the persistence of antibiotic resistant plasmids. This research provides important data that will allow us to have an easier time combating antibiotic resistance.  

Understanding an individual’s thought process as they encounter programming problems would enable the development of better techniques for teaching computer science and more comprehensive technical assessments. Prior work explored key stroke logging in writing research alongside the think-aloud study format using custom-built tools. We replicated this study format in the context of computer programming to gain insight into participant’s immediate thought process. We aimed to gain a better understanding of a participant’s mental model as they encounter computer science problems. In specific, we wanted to investigate pauses in coding and what students think before, during, and after these pauses. For this study, we used Codeitz, a custom programming tutor that allowed us to log all the participant’s timestamped input as they wrote code. We also collected audio and screen recordings of participants using the think-aloud strategy as they wrote code. We ran a pilot study that required participants (3) to answer eight programming questions, two of which involved writing code. We found some similarities in pause clustering for participants who answered the same questions. We also noticed that participants whose pauses were due to utilizing development environment affordances, identifying misconceptions, and identifying gaps in knowledge semantics exhibited more self-regulation as programmers.

Genetic diversity and gene flow are important to long-term viability in wild populations. In migratory species, gene flow (i.e. dispersal between disparate populations) is inherently influenced by the spatial and temporal components of their migrations. Recent findings have revealed the importance of fine-scale population structure in both space and time in Sockeye Salmon (O. nerka). However, the fitness consequences of this fine-scale structure are unclear. Here we evaluate the biological relevance of fine-scale spatial and temporal homing by examining their effects on a quantitative trait, individual lifetime reproductive success. Salmonids are well-known for their extensive journey from the freshwater stream where they hatch, to the ocean, and back to their home stream (i.e. ‘homing’). Homing behavior is associated with individual fitness; individuals are locally adapted to their natal streams, and dispersers between non-natal streams can have reduced reproductive success. Population structure within individual streams is generally assumed to be random (panmictic). However, individuals may be locally adapted on a finer scale than previously known, both in space (homing within their natal stream) and return timing. Fine-scale spatial and temporal homing may play a role in individual fitness; therefore, it is important to investigate this relationship. We used zero-inflated negative binomial models and a multi-generation pedigree, reconstructed from two populations of Alaskan Sockeye Salmon, to estimate the impact of homing on individual reproductive success (number of offspring per fish). Our results suggest that fine-scale dispersal in both space and time may reduce lifetime fitness. These results have broad implications for fisheries management and habitat conservation: recognizing the connection between reproductive success and return timing could inform within-season fisheries management, helping maintain the genetic diversity associated with local adaptation; likewise, recognizing the connection between individual salmon success and their habitat may promote maintaining natural heterogeneity in salmon streams.

By the late 1520s, Henry VIII’s lack of a legitimate male heir had led to a succession crisis in England. Eventually this culminated into a procession of legal and scholarly battles broadly referred to as "The Great Matter", which was the quest for the annulment of Henry VIII's first marriage. Criticisms over these proceedings by historians often decontextualize the events of the Great Matter. Moreover, the Great Matter is often portrayed as a vanity project; one that was wholly unnecessary because Henry VIII had a legitimate daughter from his first marriage. There are many flaws with this presentation of history. For one, it ignores most of the historic precedent up to the point of Henry VIII's reign for how female leadership was received, and what that reception could lead to– namely rebellion, usurpation, forced abdication, civil war, and instability. I argue that, rather than a vanity project, the Great Matter was absolutely understandable within the context of the time and place it occurred. I also argue that, rather than the near and distant future proving Henry’s anxiety over the reception of female leadership as unwarranted; such anxiety demonstrated a remarkable sense of awareness and an extraordinary prescience. My research includes the Letters and Papers of Henry VIII and a collection of other various primary source quotes relevant to the matter of female succession in the sixteenth century, and the Great Matter in particular. These were analyzed through a social and cultural lens, and also analyzed through contextualization and comparison to later relevant events.

 Twelve replicate populations of the bacterium Escherichia coli have been evolving in Lenski's Long-Term Evolution Experiment (LTEE) for over 67,000 generations in a shared nutrient limited environment. The evolved bacteria grow 70% faster than their ancestor but experience a decrease in number produced during a growth cycle. This is consistent with a trade-off between growth rate and yield (here defined numerically). We explore if populations are constrained by their previous ecolution, and if populations with high growth rate can evolve to have a higher yield (and if so, does this happen at a cost to growth rate?). We do this by adding population structure to growing populations, where selection is relaxed on growth rate and strengthened on yield. Water-in-oil emulsions provide a structured environment where millions of nutrient-filled droplets are isolated by an oil phase. We manipulate population structure by inoculating droplets with either one bacterial cell (low starting density) or more than two bacterial cells (high starting density). We observe that selection acts on faster growing cells in our high density emulsion treatment and higher yield cells in our low density emulsion treatment. We also observe a change in cell size: cells in the high density emulsion treatment get bigger over time, and cells in the low density emulsion treatment get smaller. We explore if there is a relationship between cell size and growth rate/yield trade-off.

Extra chromosomal pieces of DNA, called plasmids, exist within bacterial populations. Many scientists believe that the relationship between plasmids and their bacterial hosts is mutually beneficial. Plasmids use replication machinery from their host to ensure their continued persistence. Meanwhile, the plasmid carries genes that can benefit the bacteria, such as genes that can provide resistance to antibiotics. In environments that contain antibiotics, bacteria that contain plasmids with antibiotic resistance genes would have a higher fitness and be able to survive and reproduce at a higher rate compared to bacteria that don’t carry plasmids. Contrary to popular belief, research by members in our group showed that different plasmids actually persisted in bacterial populations when they were not under selection. The purpose of this project is to see if the trend of plasmid persistence would continue in a nutrient limited environment. We performed a long term evolution experiment on three types of bacteria containing plasmids in a nutrient limited environment. Next, grew the evolved descendants in an environment containing antibiotic to see what portion of the population is still containing the plasmid. The results of this experiment will help scientists have a more holistic understanding of plasmid biology which could have implications on antibiotic treatments.

Polycystic kidney disease (PKD), commonly caused by defects in polycystin-1 or polycystin-2, results in the formation of fluid-filled cysts and progressive loss of kidney function. Our laboratory has established a cellular model for ADPKD using kidney organoids, multicellular tissue that functionally and structurally resembles the organ of interest, derived from gene-edited human pluripotent stem cells (hPSC). To address the need surrounding a cure for PKD, we have also discovered a basis for a form of treatment involving myosin. Non-muscle myosin is a protein that controls cell protrusion and adhesion; we have established that lack of adherence increases cystogenesis dramatically. We discovered blebbistatin, a non-muscle myosin (NMMII) inhibitor, is a robust inducer of cystogenesis. Our previous finding begged the question if activators of NMMII have the opposite effect and reduce cystogenesis in PKD organoids. To better understand the role of myosin, we differentiated kidney organoids from human PKD hPSCs in a 24-well plate coated with Matrigel. We proceeded with microdissecting the organoids at 3 weeks before they formed any cysts and transferred the organoids to suspension culture where they were treated with either DMSO as a control or a pharmacological myosin activator for one week. The organoids were then imaged and number of cystic organoids were quantified. The treatment using the myosin activator compound resulted in decreased cystogenesis, in terms of the size and number of cysts. Although we have yet to clarify myosin’s effect in the PKD pathway, we have identified a myosin activator as a potential inhibitor of cystogenesis. Further experimentation is to be done with other compounds such as actin activators, and proceeding with experimentation on ex vivo kidneys of mice. Our current findings suggest that the polycystin proteins positively regulate actomyosin’s contractility, therefore myosin may be an important factor for keeping kidney tubule integrity and preventing cystogenesis.

Polycystic kidney disease (PKD) affects nearly 600,000 people in the United States and it is caused by mutations in the genes that encode polycystin-1 (PC1) and polycystin-2 (PC2). These modifications are responsible for the growth of fluid-filled renal cysts that can impair kidney function over time, and lead to end stage renal disease. PC1 and PC2 have also been localized to the mitochondria, suggesting that they are responsible for regulating cellular metabolism and energy production, which can lead to mitochondrial dysfunction and increased PKD progression. Our lab uses human pluripotent stem cells (hPSCs) to generate kidney organoids that can be used to study the advancement of PKD, which contain the major proximal structures of the nephron including podocytes, proximal tubules, distal tubules, and endothelial cells. Orgnaoids that lack both PC1 and PC2 will develop cysts that can grow large enough to be seen by eye. Unfortunately, these organoids lack a collecting duct (CD) system, a crucial component of the kidney that expands greatly in PKD. To address this need, we developed a protocol to differentiate hPSCs into ureteric bud (UB) cells, the precursors of CD cells. First, we identified Dolichos biflorus agglutinin (DBA) as a key CD lineage marker in developing kidneys through immunofluorescence analysis on human kidney tissue. Then, we took undifferentiated hPSCs and investigated their ability to express DBA by treating them with a concentration gradient of small molecules known to induce kidney lineage cells. The resulting cells were stained with DBA and GATA 3, an additional, early CD marker, and we found that both markers were expressed in vitro. We will continue modifying this protocol to better study the increased metabolic rates seen in PKD, its effects in CD cells, and the mechanism behind the PC1 and PC2 pathway that leads to cyst formation.

Elevated intermuscular fat (IMF) is an indicator of metabolic syndrome and triggers the development of chronic diseases such as diabetes and heart diseases. Metabolic syndrome (MetS) includes insulin resistance, hypertension, dyslipidemia, hypercholesterolemia and abdominal adiposity. A leading hypothesis linking IMF to MetS is because skeletal muscle is the primary site of glucose metabolism. This function is impeded by the presence of IMF due to limited microvasculature perfusion to the muscle. Cancer treatment increases the ratio of intermuscular fat to skeletal muscle (IMF:SM), which indicates an investigation of IMF is warranted in patients treated for cancer. The purpose of this study to investigate the relationship between IMF, diabetes and hypertension in patients treated for cancer. We will perform a secondary analysis to examine IMF composition by magnetic resonance imaging (MRI) leveraging existing data in 143 cancer patients with stage A heart failure. This will inform us of the association between intermuscular fat, hypertension and insulin resistance in cancer patients, which is the first study to investigate this research question. Further study is needed to determine whether increased IMF in cancer patients leads to increased risk of MetS or diabetes. Furthermore, this line of work will inform future research into lifestyle interventions capable of reducing intermuscular fat, which has implications for the development of MetS in individuals treated for cancer.

Cancer is the second leading cause of death in the United States. Advanced treatment techniques and robust research have improved cancer survivorship. However, there is significant cancer treatment related morbidity and mortality with 30% of breast cancer patients presenting with heart failure symptoms that include trouble breathing, poor exercise tolerance, and fatigue. Therefore, research that aims to improve the lives of cancer survivors in this regard is needed. Excess body weight is a significant risk factor for both increased mortality in cancer patients and heart failure symptoms; however, it is unclear how fat is implicated. Intermuscular fat (IMF), fat that is located inside and between muscle groups, is a metabolically active tissue that competes with skeletal muscle for the use of oxygen, blood, and glucose. Elevated IMF has the strongest relationship with breast cancer mortality compared to any other measure of body composition. The purpose of my research is to describe differences in IMF accumulation during treatment in 143 patients receiving chemotherapy for cancer. Abdominal magnetic resonance imaging (MRI) will be used to determine total skeletal muscle, visceral fat, and IMF using Tomovision software. Images will compare total pixel surface area of each tissue to create a ratio of skeletal muscle to IMF at enrollment (0 mos) and end of study (24 mos). I hypothesize that the type of chemotherapy most strongly associated with weight loss will be linked with increased IMF during treatment. The study results will add to one aspect of a larger body of work that aims understand the mechanisms of IMF in cancer patients and its relation to cancer treatment-related symptoms. Future research should investigate interventions that aim to reduce IMF and monitor for reduced fatigue, less severe heart failure symptoms, and improved patient mortality.

The study of the behavior of multiple agents, specifically human and machine, in a dynamic environment is challenging due to the unpredictable individual behaviors. Humans will naturally formulate beliefs about the machine’s behavior, which would directly affect their future decisions. Our research aims to develop a framework for the study of human-machine dynamic interactions. With the imperfect information humans and machines have about each other and their environment, a game-theoretic approach was done to study the natural model of their interactions. We derive theoretical models for steady-state (i.e. equilibrium) and transient (i.e. learning) behaviors of humans interacting with other agents (humans and machines). We also design experiments to validate our theory. A haptic testbench, in the shape of a robotic arm, is used as a dynamic simulation platform for studying the trajectories of the human/machine interaction, allowing us to study both theoretically and experimentally. The robotic arm has a position control system that supports a wide variety of human/machine experiments. The user is provided with visual and haptic feedback, which allows for experiments to be designed to study the sensorimotor learning processes. The robotic arm is built using direct-drive brushless motors, force sensors, an open-source ODrive motor controller, and an arm lever. The motor firmware is designed in C/C++, and integrated with a user-interface in Python. With the wide variety of potential applications, we hope our research will give insights into the different natures of human motion and be a fundamental platform for technological breakthroughs in the medical field.