Environmental and Occupational Health Sciences Institute
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Deformation spines satisfy an exponential isoperimetric inequality
No full textWe prove that the barycentric spine of bounded complexity for a deformation space, in the sense of Max Forester, satisfies an exponential isoperimetric inequality. The proof gives a new application to combing rectangles once used to prove that the free splitting complex is hyperbolic. We also give new insights into the geometry and dynamics of self equivariant foldable maps as an unexpected area of study necessary to finish the proof.Ph.D.Includes bibliographical reference
The Rohingya Muslims: a Burmese folk devil
No full textStarting August 25, 2017, the Burmese military began a retaliatory campaign triggered by a handful of militant Rohingya insurgency attacks on Burmese law enforcement posts in the Northern Rakhine State in Myanmar. The military conducted a violent crackdown upon Rohingya men, women, and children, forcing over 700,000 Rohingya to flee to refugee camps in Southeast Bangladesh. Rohingya refugees fled massacres, gang rapes, torture, and arson of entire villages. Allegations of genocide and crimes against humanity are presently under investigation before two international courts.
This study investigates the complex sociohistorical context and conditions that converged over time in Myanmar, preceding the military-led mass atrocities of 2017, leaving the Rohingya population at acute risk of harm. I inquired how the Burmese military readily succeeded in this task, with widespread Buddhist civilian approval and sometimes even assistance. To explain the processes that led to the military’s successful expulsion of the Rohingya, I utilize multiple methods of qualitative data analysis. I begin with a historiographic analysis to establish a historical knowledge baseline. Then, I conduct critical discourse analyses of two strains of Burmese nationalism, traditional and religious. I conduct two additional analyses using data from 52 in-depth interviews conducted in 2019 (32 males and 20 females) in the Bangladesh refugee camps. The first is a narrative analysis of history from the perspectives of Rohingya refugees. The second is a thematic analysis of interviews to identify the most prominent themes of their lived experience in Myanmar before fleeing to Bangladesh. Contemporary narratives are analyzed through two closely related theoretical frameworks: ethnic nationalism, and ethnic conflict. The most recent years are analyzed through moral panic theory to explain how other Burmese civilians readily tolerated, even cheered, mass atrocities against the Rohingya.
Findings from this study indicate that since 2012, the Buddhist nationalism movement normalized oppression, ostracization, and expulsion of the Rohingya to new heights, enabling law enforcement groups to commit abuses before 2016-2017. The movement provoked moral panic among Burmese Buddhists and, most consequentially, Rakhine Buddhist civilians. The movement used mechanisms of moral disengagement in promoting their ideology and as a means of self-exoneration. A collective attitude of existential fear of, and contempt for, the Rohingya presence enabled the military to conduct a brutal campaign of ethnic cleansing, including areas of genocide, with domestic impunity. This study highlights the special significance of the dehumanization of Rohingya by Buddhist nationalists in enabling atrocities and suggests the power of humanization as a potential intervention strategy in moral panic situations that pose a risk for genocide.Ph.D.Includes bibliographical reference
A reverse genetic and kinetic investigation of the reductive-oxidative iron uptake pathway in Thalassiosira pseudonana
No full textIron is an essential cofactor to the photosynthetic processes of marinephytoplankton and one of their most commonly limiting resources. In chapter 1, we compare the proteomes of steady-state Fe limited Thalassiosira pseudonana and Phaeocystis globosa, two coastal algae with substantially different tolerances for open ocean Fe levels. Different Fe uptake proteins were upregulated in these two species (phytotransferrin in P. globosa, ferric permeases in T. pseudonana). These findings were then correlated with a series of kinetic Fe uptake experiments assessing phytotransferrin mediated uptake in both organisms. We conclude that unlike most marine phytoplankton, T.pseudonana does not engage in phytotransferrin mediated Fe uptake, consistent with its recent freshwater ancestry. One model for iron uptake in diatoms requires a ferric reduction step at the cell surface. In yeast, a similar reduction step is part of the reductive-oxidative Fe uptake pathway through a ferric reductase protein (FRE). A ferroxidase-ferric permease (FET3/FTR) complex then subsequently binds, oxidizes, and transports Fe(III). FET and FTR are co-obligate partners, and the yeast permease cannot access Fe(III) directly from the dissolved milieu. Homologous proteins are predicted in the genome of model diatom T. pseudonana, including two FTRs but only one FET. In chapter two, we investigated the role of the putative ferric permeases (FTR1, FTR2) and the ferroxidase (FET) using reverse genetics. FTR transcriptional knock-down clones grew slower under steady-state iron limiting conditions. GFP chimeras of both proteins, under native promotion, were localized at the cell surface and upregulated in limiting Fe. FET knock-out mutants had no phenotypic difference with wild-type when growing in Fe limiting conditions. We hypothesize that one or both permeases engages in direct uptake of Fe3+ independent of a ferroxidase.M.S.Includes bibliographical reference
Tar-Baby : a novel
No full textTAR-BABY is a novel that utilizes folklore and speculative storytelling to tackle issues of community displacement, generational trauma within Black American communities, and self-definition in a society that antagonizes otherness. In this contemporary reimagining of the Tar Baby folktale, a young Black woman named Baby appears in a gentrified Midwestern neighborhood in the midst of a political battle between the older, white patriarch Eugene Fox and a young, charismatic Black man named Lucky Foote. After touching Baby, Lucky becomes preternaturally drawn to her. When Baby comes into contact with others in the neighborhood, she finds them similarly desperate to touch her. Seeking answers, Baby learns a devastating secret about her origins that forces her to wrestle with her humanity and sense of self.M.F.A.Includes bibliographical reference
The Rock City Crew
No full textThe Rock City Crew is a Young Adult, Speculative Fiction novel set in a futuristic San Francisco Bay Area, focusing on a group of QTBIPOC (Queer, Trans, Black, Indigenous, People of Color) teenagers who have special abilities and are being hunted by the government. It follows two protagonists, Syren, the leader of the Rock City Crew and Quinn, their newest member. In a time where in the real world, QTBIPOC folks are having basic human rights questioned, debated and even stripped away, I have strived to use this thesis project to explore and examine a few key ideas. What does resistance look like when laws are being passed against us? What does community look like when we are out of spoons and out of money as we pass around the same $5 in mutual aid? How do we choose to wake up every day and live our full authentic selves and fight for our own rights and those of our peers, no matter the risk? These are the questions this thesis seeks to engage with.M.A.Includes bibliographical reference
Methods for nonconvex nonsmooth conditional stochastic optimization
No full textIn this dissertation, we consider non-convex non-smooth stochastic optimization problems involving an expected value of a nonlinear function of a base random vector and a conditional expectation of another function depending on the base random vector, a dependent random vector, and the decision variables. We call such problems conditional stochastic optimization (CSO) problems that arise in many applications, such as reinforcement learning, uplift modeling, contextual optimization, etc. We introduce two stochastic methods to solve constrained CSO in specific situations.
The first algorithm is called the Functional Model Method. We propose a specialized single time-scale stochastic method for nonconvex constrained conditional stochastic optimization problems with a Lipschitz smooth outer function and a generalized differentiable inner function. In the method, we approximate the inner conditional expectation with a rich parametric model whose mean squared error satisfies a stochastic version of a Łojasiewicz condition. The main feature of our approach is that unbiased stochastic estimates of the directions used by the method can be generated with one observation from the joint distribution per iteration. The directions, however, are not gradients or subgradients of any overall objective function. We prove the convergence of the method with probability one, using the method of differential inclusions and a specially designed Lyapunov function, involving a stochastic generalization of the Bregman distance.
The second algorithm called the Value Function Learning, focuses specifically on a control problem for a finite-state Markov system whose performance is evaluated by a coherent Markov risk measure. In this case, the outer nonlinear function is the sum of squares. In this problem, we also use a specialized functional model. For each policy, the risk of a state is approximated by a parametric function of its features, thus leading to a lower-dimensional policy evaluation problem, which involves non-differentiable stochastic operators. We introduce mini-batch transition risk mappings and use them to derive a robust value function learning algorithm for Markov policy evaluation. Finally, we discuss structured policy improvement in the feature-based risk-averse setting.
We present numerical experiments for both methods to illustrate their robustness and viability.Ph.D.Includes bibliographical reference
Three essays on the information-providing function of financial markets
No full textThis dissertation consists of three essays on the information-providing function of financial markets, with evidence from the VIX futures, CDS options, and stock markets.
The first essay examines how the information from political events influences the VIX futures term structure. Focusing on the chance of policy changes, this study examines its impact on expected market uncertainty through the recent U.S. presidential elections. This study applies the VIX futures term structure and unveils both long-term and short-term impacts of the chance of policy changes: In the long term, the chance of policy changes elevates the convexity of the term structure, increasing concerns about future market volatility. In the short term, it changes the shape of the term structure around the event. Consistent findings are obtained from national polls, battleground states, and betting markets.
The second essay examines the information-providing function of the index CDS (CDX) options market and uncovers characteristics that make the market a suitable venue for information-based trades: represented by its opacity, large trade size, and surged use in crises. More importantly, this study designs a new measure based on CDX options volume and demonstrates its predictive ability for the next-day S&P 500 index returns during the COVID-19 pandemic and the high inflation period in 2022. The predicting role reveals the information flow from institutional investors to public investors and has important implications for market efficiency.
The third essay examines the impact of the Fed’s information on the stock market by unveiling incremental changes in market reactions across the Fed’s series of FOMC announcements. This study describes it as “the cumulative effect”, with strong initial impacts on market reactions moderated over the series of the Fed’s announcements. More importantly, this study highlights the significant role of the cumulative effect in stabilizing the initial strongly negative market reactions. The effectiveness of the cumulative effect is validated through analyzing intraday stock market reactions to the series of policy announcements and Press conferences during the COVID-19 pandemic and the 2022–2023 inflation. The exploration of the cumulative effect highlights the Fed’s significant role in shaping investors’ views and stabilizing the economy.Ph.D.Includes bibliographical reference
Bridging the gap: the role of nostalgia in mitigating existential
No full textFeeling existentially isolated (EI) causes a debilitating impact on one’s psychological well-being (PWB). Grounded in the regulatory model of nostalgia, I propose that nostalgia serves as a means to regulate the subjective experience of EI, fostering feelings of shared understanding and common existence. To test this, participants were induced to experience either existential isolation or existential connectedness and retrieve an unspecified memory. Participants then completed measures on nostalgia, affect, gratitude, psychological thriving and nostalgia proneness. The results indicated that the experimental manipulation was not successful in inducing EI and did not predict nostalgia. Although there was no statistical suppression of the effect of EI on PWB, nostalgia significantly predicted PWB. These findings highlight the difficulty in manipulating feelings of EI and underscore the dire need for further investigating ways to foster shared understanding among diverse individuals, in order to mitigate EI. It also replicated the positive association between nostalgia and PWB, thereby reinforcing the highly restorative nature of nostalgia.M.A.Includes bibliographical reference
Dermal pharmacokinetics of topical and transdermal drugs and their PBPK modeling
No full textTransdermal drug delivery (TDD) has been an attractive route of drug administration for many years and has been proven to have higher patient compliance when compared to oral and needle-based administration. TDD provides several advantages over other administration routes such as patient self-administration, non-invasive therapy, reduced side effects, and much reduced toxicity due to low systemic exposure. Over the years, remarkable advancements have been made in TDD with successfully delivering certain hormones and drugs such as siRNAs, peptides, and others, which are often degraded in the gastrointestinal tract when administered orally.Despite the advancements in TDD, the administration technique has still not reached its full potential. It has been relatively challenging to study the pharmacokinetics of the drugs administered topically. This has been mainly due to the limited ability of drugs to cross the stratum corneum (SC), the outermost layer of the skin. SC is made up of dead keratinocytes (corneocytes) surrounded by lipid matrix. This architecture of SC is commonly known as the “brick and mortar” model, where the bricks represent the corneocytes and the mortar the lipid matrix. Although this is the thinnest layer of the skin, it is the toughest. Its primary function is as a physical barrier to prevent the entry of foreign compounds into the body. Due to this barrier effect, it is challenging to deliver adequate amounts of drugs across the SC.
Due to some recent advancements, the barrier of the stratum corneum has been overcome to some extent with various approaches such as chemical and physical enhancement techniques. However, due to limited drug absorption and perfusion into the systemic circulation, many of the commonly used analytical methods are not able to successfully quantify extremely low drug levels that are required for plasma concentration-time profiles. Therefore, conventional pharmacokinetic models cannot be employed to determine the pharmacokinetic parameters.
The goal of this project is to study the dermal pharmacokinetics of drugs to parameterize, optimize, and validate dermal physiologically based pharmacokinetic (PBPK) models which can be used with the full-body PBPK model to predict and estimate the pharmacokinetic parameters that cannot be determined through in vitro or in vivo studies. The dermal PBPK model, which was initially built by our collaborator CFD Research Corporation (Huntsville, AL 35806, USA) was used in these studies. This multi-compartment dermal PBPK model incorporated the complex structure of the SC. This model integrates the drug release and ex vivo studies to optimize the mechanistic model.
To conduct this project, two classes of drugs have been studied using “bioequivalent” formulations as deemed by the FDA – adapalene (topical application) and desoximetasone (transdermal application). Adapalene is a third generation retinoid which has a logP of 6.9. This lipophilic compound has a tendency to interact with the lipids in the SC and the sebum found in the pilosebaceous unit. It is primarily used for the treatment of acne vulgaris. Similarly, desoximetasone, which has a logP of 1.83 was studied with two formulations both available over the counter which are deemed to be “bioequivalent” by the FDA. These formulations were used to study the release kinetics of the drug in vitro. These release profiles were used to determine parameters such as permeability and diffusivity using the Brunner modification of the Noyes-Whitney equation. The use of the Noyes Whitney equation for modeling release studies is advantageous due to its origins in Fick’s laws of diffusion. This significantly simplifies the model by maintaining consistency and minimizing complexity across the compartment. In addition, this helps in minimizing potential errors and streamlining the analytical process and assists in fine tuning diffusivities and partitioning coefficients which are then leveraged into the dermal PBPK model.
The ex vivo studies were conducted using human cadaver skin samples obtained from U.S. accredited skin tissue banks. These studies were employed to study the absorption, distribution and flux of the drugs using Fick’s law of diffusion. Fick’s law of diffusion describes the transfer of a drug from one compartment to another over time, separated by thin membrane/ skin of thickness “x” per unit area. Mathematically, the permeation flux can be written as: (Matharoo et al., 2024) Equation 1: Mathematical representation of Fick’s law of diffusion where:J is the flux
Q is amount of solute
A is unit area of membrane/skin surface
C is concentration of solute
dx is thickness of membrane/skin
dC/dx is concentration gradient (Cs)
t is time
This equation indicates that the transport of drug is driven by the concentration gradient across two compartments (donor and receptor).
The skin and receptor concentration-time profiles were determined over 24 to 36 hours. The skin layers were mechanically separated to study the cumulative distribution of drugs. The dermal PBPK model included the skin layers: SC, viable epidermis (VE) and dermis. The skin thickness and weights of skin used experimentally were used in the model to closely match the experimental data, providing robust platform and to study drug delivery and skin absorption dynamics.
To study the effect of adapalene on acne disease, a comparative clinical study was performed in collaboration with Robert Wood Johnson Hospital. In this randomized study, the adapalene gels were applied on the malar cheek of the patients with mild to medium non-inflammatory comedones. The gels were reapplied every 24 hours in a 48-hour study. These studies gave us an insight into the effect of adapalene on the pilosebaceous unit and the SC. The changes in the size of these were studied to determine the effect on sebum degradation and unclogging the pilosebaceous unit and the desquamation rate of SC. A systems biology model for acne is currently being built using the information from the clinical study and the data from the literature. This model has the structure of the epidermis accounting for stratification of epidermis by incorporating the proliferation and differentiation of keratinocytes in the epidermis, connected with the sebaceous gland. Acne formation due to sebum production and dead cell accumulation in the pilosebaceous unit and its effect on bacterial growth and the innate immune system will be studied. The effect of bioavailable adapalene on these processes will be incorporated in this model by integrating the previous PBPK model.Ph.D.Includes bibliographical reference