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Characterizing the interaction of the Bacillus subtilis ClpC chaperone with a novel sporulation adaptor protein
No full textProtein degradation is a complex process that affects biological pathways. Proteolysis in all organisms is carried out by the ATP-dependent AAA+ proteases, including in the bacterium Bacillus subtilis, which undergoes sporulation, resulting in the formation of a metabolically dormant cell type called a spore. The molecular mechanisms that drive metabolic dormancy are poorly understood, but research suggests that this may involve the degradation of key metabolic enzymes in the forespore. Previous lab members have identified an uncharacterized gene micA expressed in the developing spore; its knockout displays phenotypes consistent with increased metabolic capacity. Our model suggests MicA functions as an adaptor protein, recruiting key metabolic enzymes to the chaperone-protease, ClpCP for degradation. MicA interacts with an interface of the ClpC N-domain at 3 different electrostatic sites confirmed by a co-crystal structure. In this project, we hypothesize that the lysine at position 12 (K12) of ClpC is important for the interaction of MicA with ClpC. Alteration of ClpC K12 did not disrupt overall ClpC function, but rather specifically blocked the toxicity of micA during vegetative growth and, like a mutant lacking micA, caused increased gene expression in the developing spore. Therefore, the K12 site on the ClpC protein is necessary for MicA and ClpC interaction.Biological Science
Indoctrination, Insulation, and Closed-Minded Belief: Easy as ABC
No full textIn this thesis I argue that indoctrination is closed-minded belief caused by epistemic insulation, where epistemic insulation is a belief that motivates closed-mindedness for any reason. I first consider and reject previous accounts of indoctrination which define it by intention, method, outcome, and content. I next consider Rinalli’s definition, which functions as the basis of my own definition, but claims that epistemic insulation motivates the pupil by appealing to their desire to be rational and moral. Finally, I present and defend my own account of indoctrination which differs from previous accounts by claiming that epistemic insulation can be motivated by reasons beyond a desire to be rational and moral.Philosoph
Biking San Juan Island: Creating a Resilient & Livable Community Through Bike Infrastructure
No full textMy thesis targets the rural and urban planning of San Juan Island and strives to provide a set of design strategies and proposals to equip the island with bike infrastructure. San Juan Island is nestled in the northwestern corner of Washington State and is only accessible by ferry from the mainland and is a major tourist attraction. The island is home to approximately 8,000 year-round residents. The summer population spikes to 20,000 with seasonal residents and visitors. Of these visitors, a significant amount travel via bicycle to tour the island and take in the scenery. However, San Juan Island has virtually no bike lanes which means drivers and riders are forced to share rural roads.
I grew up on San Juan Island, and I have always been complacent to the fact that the island and our town, Friday Harbor, do not accommodate bikes. This is the model I have seen all across the United States. However, after studying abroad in Copenhagen and spending six months riding around an urban setting designed from its core for bikers, my perspective on what a community can and should provide for all non-car-users has shifted drastically. Bike lanes can be integrated seamlessly into an urban fabric. This makes biking enjoyable and accessible for all community members. My goal is to take the strategies and design practices I have experienced in Denmark and use them to shift my town’s emphasis from cars to walkers and bikers. These two modes of transportation create human experiences that connect us with our surroundings in an intimate and environmentally conscious manner.Architectural Studie
Simulating flow behavior of soft particles in a quasi-two-dimensional silo under varying gravity
No full textSystems as diverse as sand, crowds of people, and the rings of Saturn can be classified as granular materials. Omnipresent in our daily lives, in nearly every field of science, and part of billions of dollars per year in industry, we know surprisingly little about how granular materials behave. For systems such as gases we can take the understanding that atoms will bounce off of each other and the walls and derive the Ideal Gas Law. No such local behavior to bulk behavior scaling exists for granular materials. Due to factors discussed within such as unequal force distribution, there is a mid-“meso-scale" present that disrupts our ability to predict bulk behavior. As a result, granular systems can behave both in a liquid-like manner when they flow or a solid-like manner when they jam.
In this thesis, we study the specific geometry of a silo, which can be simply conceptualized as a container, filled with a granular material, that has a outlet (aperture) in the bottom – thus allowing the grains to flow out under the force of gravity. This ostensibly simple system is reasonably well described by an equation called the Beverloo equation, but only for typical systems: hard particles at regular Earth gravity (9.81m/s2). Understanding how systems of soft particles flow is important for building a comprehensive model of granular flow and for applications in fields such as biology. Understanding how granular materials behave in different gravity is essential for space exploration and extra- planetary science. For example, if we want to land a spacecraft on an asteroid that has its own microgravity, we need to understand how the grains that make up the surface of that asteroid will behave in a system very different to what we have on Earth.
In order to study these questions, we use molecular dynamics (MD) simulations through the software LAMMPS (Large Atomic/Molecular Massively Parallel Simulator). This software uses Newton’s law of motion and a model of particle contact to output position, velocity, and force data for each particle at every timestep. Simulating our system allows us to easily vary particle stiffness, gravity, and the diameter of the aperture. We study a quasi-two-dimensional system made up of a single vertical layer of spheres. We present our results on local measurements such as granular temperature, mesoscale measurements such as velocity profiles, and bulk measurements such as flow rate. We also discuss pressure waves that we observed within our system. We present a hypothesis for a relationship between granular temperature and deviation from the Beverloo equation. We also observe that a dimensionless ratio of gravity and stiffness, Γ, collapses many of our measurements and reveals trends.Physic
Familial Influences on Perceptions of Mental Health and Mental Health Support Seeking in Black Young Adults
No full textMental health in the Black community continues to be overlooked by psychological research. Due to factors such as historical trauma, generational trauma, and lack of knowledge, mental health, and mental health stigma are also significantly overlooked by the Black community (Abdullah & Brown, 2010; Krow, 2020). Individual shame and pressure from family members to conceal mental health struggles frequently influence individuals to isolate themselves and avoid seeking necessary support. The purpose of this study was to investigate the ways in which familial attitudes and behaviors during upbringing have shaped young Black adults’ attitudes and perceptions toward mental health and mental health support seeking. Data collected using a qualitative questionnaire and follow-up interviews with 16 participants revealed that mental health stigma (commonly defined as social judgment, degradation, and devaluation) and familial perceptions have a strong influence on how the Black community, and specifically Black young adults, talk about and address mental health (Abdullah & Brown, 2010). In addition, it was found that newer generations (such as Millennials and Gen Z) of Black young adults are more willing to ask for support and/or seek treatment, despite negative experiences with family when it comes to mental health struggles.Psychology & Educatio
Transportation Market Segmentation via Latent Class Analysis
No full textPublic transportation is a primary method of mobility within and between communities for many people. Transportation systems can involve a variety of transit modes and routes, such as fixed-route bus lines or on-demand van services. The usefulness of these services largely depends on how adequately they meet the wants and needs of nearby populations. Market segmentation is a common strategy employed by transit organizations to divide their target population into various groups based on transit preferences, socio-demographic factors, and more. These segments can then be analyzed by transit planners to develop targeted routes, policies, and marketing strategies. In this paper, we introduce latent class analysis (LCA) as a tool for transit planners to rigorously perform market segmentation. In addition to an overview of the method, we estimate and analyze a toy latent class model to illustrate various mechanics of LCA. Lastly, we perform a case study analyzing transit preference market segments in the Pioneer Valley Transit Authority's (PVTA) Northern service region. Our results suggest the existence of three latent classes with members of each having distinct attitudes towards transportation and PVTA's services.Mathematics & Statistic
Quantification of Autophagy in the Fat Cells of Drosophila Fed BHB Supplements
No full textThe ketogenic (keto) diet has been popularized in the media. However, it
has also been prescribed to children and adults with drug-resistant epilepsy
(Liśkiewicz et al., 2021; Ułamek-Kozioł et al., 2019). After being on this diet,
patients often saw decreased or reduced seizure occurrence (Ułamek-Kozioł et al.,
2019).
While on a keto diet, the body produces ketone bodies, which may impact
the diet’s effect on seizure reduction (Ułamek-Kozioł et al., 2019). Some previous
studies in mice have suggested that ketone bodies can increase autophagy, which
positively impacts health and helps maintain cellular homeostasis (Liśkiewicz et
al., 2021; Xiang et al., 2023).
While the keto diet can be a good treatment for those with drug-resistant
epilepsy, it has side effects such as vomiting, abdominal pain, fatigue, and kidney
stones (Xiang et al., 2023; Ułamek-Kozioł et al., 2019). Using ketone body
supplements as an alternative treatment to the keto diet would avoid unfavorable
side effects. It would only work as an alternative if ketone body supplements
provided the same beneficial effects as the keto diet.
I analyzed the fat body cells of Drosophila melanogaster to determine if
there were increased rates of autophagy in larvae fed a diet supplemented with
BHB (ß-hydroxybutyrate - a ketone body) compared to larvae fed a control diet. I
generated images using a Confocal Laser Scanning Microscope, and they were
then analyzed using Cell Profiler to determine if the two treatments had
statistically significant differences.
After statistical analysis (T-test) of the difference in average puncta per
nucleus between the two treatments, the resulting p-value was 0.397. This p-value
is greater than 0.05, indicating that the differences between the BHB and control
treatments were insignificant.Biological Science
FEMALE SYMBOLISM: Translation and Interpretation of Selected Works of Mu Shiying
No full textWhen it comes to the early 20th century, China—the forbidden land, the Eastern fantasy— was forced to open the gate and “welcome” its unpredictable future. On the one hand, the drastic social, political, and cultural changes paved the way for modernist thinking and lifestyle. Yet on the other hand, ongoing wars and ever-increasing tensions worldwide had broken down people’s perception of ordinary civil society and became the hotbed for hedonism, nihilism, and even hermeticism. In the early 20th century Shanghai, rapid modernization brought people a seemingly fantastic newborn world—a world full of awakened desire, love, and fleeting happiness. Thus, the notable change in lifestyle and outlook attracted many young writers, whose stories primarily focused on people’s turbulent city lives and romantic relationships with modern Chinese women. Among those talented young writers was Mu Shiying 穆時英 (1912-1940), the rising star of Chinese modernist writings, who vividly illustrated the bizarre and motley metropolitan life in his unrivaled avant-garde writings and deliberate depiction of sensations. Throwing himself into the world of literature, Mu lived a modest life while depicting the luxurious yet unsettled city life. Later some of his modernist stories, such as “Five in a Nightclub 夜總會裡的五個人,” “Shanghai Fox-trot 上海狐步舞,” and “Poles Apart 南北極” outstand in Chinese modern literary world.
Because of Mu’s contentious political standing during wartime, a large part of his literary works remained undiscovered until the 1980s. However, it can never be denied that Mu is one of the most brilliant early Chinese modernist writers, who had a significant impact on later contemporary writers such as Eileen Chang and Mo Yan. When it comes to the 21th century, scholars such as Leo Ou-fan Lee and Shu-mei Shih have introduced Mu Shiying and his masterworks to Western audiences. In their researches, Lee and Shih thoroughly illustrated the short but unrivaled life of Mu Shiying and his adventure in literature, modernity, as well as a semi-apocalyptic world. Appreciating their works on Mu’s life and legacy, I have noticed that the images of female characters in Mu’s work have been rarely discussed or analyzed. Though female characters in Mu’s short stories vary from socialites to religious figures, they still naturally, consistently possess a strong sense of unreality. The unreality—even fantasy—has made Mu’s female characters divorced from reality and become literary symbols, which subtly blur the boundary between fantasy and reality, and profoundly embody sexuality, hedonism, and even serenity. Thus, I was encouraged to translate another four short stories of Mu, which profoundly involve the utilization of female symbolism. This thesis will provide a thorough explanation of the time and cultural condition of 1930s Shanghai as well as Mu’s extraordinary yet turbulent life. Through analyzing Mu’s depictions of women as symbols, allusions, and images, I argue that the female characters in Mu’s work are highly abstracted and become symbols of desire, of nostalgia, of peace, and of hedonism.Asian Studie
Investigating the Role of the RAMOSA3 Gene in Brachypodium distachyon
No full textUnderstanding the genes that regulate floral organs in the Poaceae, the
grass family, could increase grain production, contributing to food
security. Species in Poaceae have diverse floral morphologies. Floral organ
suppression contributes to this diversity. Zea mays (maize) has unisexual,
staminate flowers containing pollen grains and unisexual pistillate flowers
containing ovules. RAMOSA3 (RA3) and GRASSY TILLERS1 (GT1) are
two genes that regulate carpel suppression to create staminate flowers. ra3
mutants have partially enlarged carpels and increased axillary branching.
gt1;ra3 double mutants also have enhanced branching and enlarged pistils
with silks emerging from the tassel. Enhanced branching suggests that
RA3 regulates axillary meristem suppression in addition to carpel
development.
Another grass model system, Brachypodium distachyon (brachypodium),
has bisexual flowers with stamens and pistils. Brachypodium and maize
have orthologs of the RAMOSA3 gene, but why do they have different
floral sexualities? My project aims to discover if RA3 has a conserved role
in controlling floral organ suppression and inflorescence branching in
grasses. I investigated the role of the RA3 homolog in brachypodium
using CRISPR/Cas9 and the sodium azide mutant line NaN372. The
transformed brachypodium did not have any CRISPR edits. However,
NaN372 has an amino acid substitution in the RA3 gene. The mutant
phenotype suggests that Bdra3 mutants do not have more flowers than the
wild-type, contrary to what I predicted if RA3 function is conserved.Biological Science
DEVELOPMENT OF CELLULOSE-BASED OXIDATION SENSITIVE DRUG DELIVERY VEHICLE
No full textBiopolymers are an attractive avenue for drug delivery applications due to
their abundance, biocompatibility, sustainability, and flexible modification.
Cellulose-based materials are especially appealing, but their development is often
hampered by the poor solubility of their parent polymer. Hydrophobic groups can
be reversibly grafted onto a biopolymer to make oxidation-sensitive solubility switching materials.
While cellulose has a wide range of applications, from medical applications,
such as wound healing devices, to packaging materials, there have been fewer
studies on using modified cellulose as a targeted drug delivery vehicle. This
project expands on the current knowledge of cellulose modifications and
optimizes the creation of modified cellulose-based drug delivery vehicles.
Reactive oxidation species (ROS) sensitive groups were substituted on
cellulose to make hydrogen peroxide-responsive hydrophobic films and
microparticles. The modified cellulose was prepared through a solution-phase
reaction. The modified polymer can be fashioned into microparticles or films,
which were investigated to encapsulate hydrophobic cargo and release the
payload under oxidizing conditions. The new material may hold promise in drug eluting depot formations like stents, sutures, or beads.
The project successfully developed an oxidation-sensitive modified
cellulose drug delivery vehicle. Four ROS- sensitive groups (pinacol-modified
aryl-boronic ester, pinanediol-modified aryl-boronic ester, thioether, and
thioester) were grafted onto cellulose. Thioester-modified cellulose was oxidation
sensitive and could be formulated as microparticles. Nile red and rhodamine 6G
were encapsulated in thioester-modified cellulose to determine if the polymer
could hold therapeutics. SEM imaging revealed that the particles formed by the
nile red encapsulated polymer were independent and uniform with a diameter of
500nm. Due to time limitations, the unloaded polymer was not imaged but it can
be theorized that the diameter is less than 500 nm.Chemistr