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Actuarial fairness: what does it mean and when is it desirable?
No full textActuarial fairness is one tool for setting premium prices within an insurance programme. This is typically understood as what happens when individuals in an insurance pool pay premiums that are consistent with their respective levels of risk for health-related expenditures. For example, under actuarial fairness a smoker or someone with the BRCA genetic mutation (both of which are risk factors for cancers) might pay a higher premium for health insurance than a non-smoker or someone without BRCA, all things being equal (including their respective life expectancies), due to the increased risk of the former for expensive cancer treatment. But, as I will show, this paradigmatic case is just one of many ways in which actuarial fairness manifests and other definitions may demand a different distribution of premiums; nor is actuarial fairness an appealing account of fairness in health insurance, on any understanding of that notion. In Chapter 1, I will show that actuarial fairness has a range of plausible definitions; some recommend premium distributions that are incompatible with each other and none is obviously superior. For instance, Kenneth Arrow’s definition of actuarial fairness explicitly rejects administrative costs as part of the actuarially-fair prices, leaving most real-world cases of health insurance premiums actuarially-unfair while other definitions include administrative costs as actuarially-fair. Hence, under some definitions of actuarial fairness, insureds could always be said to be treated in an actuarially-unfair manner. In Chapter 2, I show that none of our plausible definitions are without problems and what is actually practiced turns out to be a morally repugnant version of actuarial fairness. In Chapter 3, I argue against the positive arguments that proponents of actuarial fairness typically provide that are typically couched in liberty and efficiency. In Chapter 4, I provide an assessment of various jurisdictions in terms of their use of actuarial fairness and its moral (im)permissibility. In so doing, I aim to show the different uses of “actuarial fairness” across the world as well as show that its use is more pervasive than typically thought and deeply ingrained in state policy. Furthermore, the prima facie degree of moral permissibility may depend, in part, on existing structures that care for the worse-off. One might think that naming our specific notion of actuarial fairness from among the many options available would resolve all these issues. But I show that complications affect all sharpened notions of actuarial fairness. Ultimately, I conclude that so-called actuarial fairness is misguided and often discriminatory when used to decide health insurance policy, and that it should be considered unfair even by proponents of actuarial fairness themselves.Ph.D.Includes bibliographical reference
Development of structure-based machine learning approaches for protein interfaces
No full textProtein interfaces play vital roles as essential hubs in executing diverse protein functions within various biological processes, including proteolytic cleavage, enzymatic activities, viral attachment and entry, signal transduction, and transport. Machine learning (ML) has rapidly grown into one of the most popular and promising areas for predicting interface specificities efficiently and accurately. This dissertation aimed to use interface structures in machine learning for specific interface function prediction and designs. It focused on developing interpretable and generalizable models, with broad applications for various interface systems. The study also explored the importance of data quality, variety, and quantity for learning.
To understand protease specificities, we need to quickly grasp the full substrate landscape of proteolytic cleavage and comprehend the underlying biological basis for functionally distant proteases. Herein, we introduced Protein Graph Convolutional Network (PGCN), a novel approach that leverages a physically-grounded, structure-based molecular interaction graph to capture molecular topology and interaction energies for the prediction of protease specificity. We showed PGCN’s high accuracy in predicting specificity landscapes for various variants of two model proteases, namely the NS3/4 protease from the Hepatitis C virus (HCV) and the Tobacco Etch Virus (TEV) protease. Through node and edge ablation tests, we identified key elements within the graph that contribute significantly to specificity prediction, aligning with known biochemical constraints governing protease:substrate recognition. We further employed a pre-trained PGCN model to guide the design of TEV protease libraries for cleaving non-canonical substrates, achieving excellent agreement with experimental cleavage results. Most importantly, we found the model can accurately assess designs featuring diversity at positions not present in the training data.
We expanded PGCN's use with CleavEX, a user-friendly pipeline for preprocessing deep sequencing data, enabling efficient categorization of substrates for various enzymes. It successfully prepared data for six 3C-like proteases, achieving state-of-the-art accuracies with PGCN models. We also explored PGCN's potential in predicting binding interactions, specifically between the RBD of the SARS-COV-2 spike protein and ACE2, as well as PDZ domain binding.
To further explore data quality, we analyzed small molecule ligand data from the Protein Data Bank, identifying distribution and dependencies of ligand structure quality metrics. This led to composite ligand quality indicators for simplified ligand selection in drug design. Additionally, we introduced a novel all-and-subsample clustering framework to handle large-scale clustering problems, requiring human review for biological significance verification. The process can be extended to analyze various types of large datasets.
Our research in this dissertation presents promising solutions for interface prediction, design, and structure quality assessment using structure-aware machine learning approaches. These findings offer possibilities for developing customized protein editors capable of selectively and irreversibly modifying specific targets, opening new avenues for future therapeutic applications.Ph.D.Includes bibliographical reference
Effects of chunking intervention on enhancing geometry performance in high school students with mathematics learning difficulties
No full textGeometry education is an important aspect of STEM education and career development, but it is often overlooked in K-12 education in the United States. Although there is some research on teaching geometry to students with learning difficulties at the elementary level, there is a lack of research on teaching advanced geometry skills at high school levels. Chunking is a strategy that can help reduce the cognitive load demanded in the processing of information, and it has been applied as a testing accommodation for high school students with math learning difficulties in geometry assessments. This study aims to expand upon the existing literature by examining the effect of chunking as an intervention, rather than just a testing accommodation, on the geometry performance of high school students with math learning difficulties.
The study used a multiple probe design across participants and address the following research questions: (a) To what extent will the chunking intervention improve the geometry performance of high school students with math learning difficulties as measured by a proximal measure (i.e., geometry problem solving probes related to lines and angles)? (b) To what extent will the effects of chunking intervention maintain two weeks after the conclusion of the intervention as measured by the proximal measure? (c) To what extent will the students be able to generalize their geometry knowledge to distal measures, such as geometry proof related to lines and angles, sample items from the NJSLA high school test preparation for geometry, and the KeyMath-3 geometry subtest? (d) What are the perspectives of the high school students with mathematics learning difficulties about the chunking intervention?
Three high school students with difficulties in learning geometry participated in this study during an in-school intervention program at a high school in New Jersey. The intervention was implemented by the interventionist and a trained undergraduate research assistant, and consisted of 6 sessions, divided into three units: (a) a unit on angles and related properties, (b) a unit on parallel lines (c) and a unit about perpendicular lines. The entire intervention, including the baseline and post-test phases, lasted approximately two months, depending on the participants' availability and their sequences of introduction into the intervention. The treatment's fidelity was monitored and reported, and students' perspectives on the chunking intervention was evaluated through a social validity measure at the conclusion of the intervention. The outcomes of visual analysis indicated that participants improved their performance during the intervention phase as compared to the baseline phase in the geometry problem-solving test's proximal measure. Compared to their corresponding scores in the baseline, most of the participants’ scores in the posttest showed significant enhancements on the transfer measures. Participants who underwent the maintenance tests sustained elevated performance levels even two weeks after the conclusion of the intervention. Individual differences in students’ responding to the intervention were discussed with regard to their pre-requisite skills and conceptual knowledge of the geometry concepts. The researcher then discussed the limitations, contributions to the literature, implications for practice, and future research in teaching geometry, and recommended that chunking strategy should be integrated with, rather than replacing, concept instruction.Ph.D.Includes bibliographical reference
A behavioral and physiological analysis of the modulatory role of the N/OFQ system in neuroinflammation
No full textIt is well established that the brain and the immune system communicate bidirectionally to influence behavior. This is exemplified by studies showing that environmental and psychological processes affect immunity, and in turn, immune-mediated inflammatory stressors affect central nervous system (CNS) function and behavior. In this context, the purpose of the current dissertation is to investigate the potential role of the neuropeptide Nociceptin/OrphaninFQ (N/OFQ) and its receptor NOP in the regulation of sickness behavior and associated neuroinflammatory signals. The overarching hypothesis was that the N/OFQ system serves to regulate the effects of inflammation on the CNS, limiting disruption of ongoing behavior. This was investigated using motivational, exploratory, and consummatory behavioral assays paired with ELISA and qPCR immunoassays to determine proinflammatory cytokine profiles in wildtype and NOP receptor (NOP KO) deficient mice challenged with the endotoxin LPS. The results of delivering LPS either systemically or centrally revealed major differences in the magnitude and pattern of expression in cytokine mRNA within the hypothalamus and hippocampus, as well as in the peripheral inflammatory response. Furthermore, it was found that in wildtype C57/BL6 mice, systemic LPS did not alter peripheral splenic proinflammatory cytokines in NOP KO mice compared to WT. However, when LPS was administered centrally, IL-6 was only elevated in WT LPS-treated mice, but not in mice with inhibited NOP function. After systemic LPS challenge, il1 and tnf mRNA transcripts were elevated in the hypothalamus in LPS-treated mice regardless of genotype, yet after central LPS, il1 and tnf were elevated 5-fold in the hypothalamus of NOP-inhibited mice when compared to saline controls. Behaviorally, NOP KO mice showed decreased neophobia in both exploratory and consummatory behaviors, although in a progressive ratio task for sucrose reward they showed greater persistence in responding. These results suggest a complex modulatory role of the N/OFQ system in neuroinflammation and related exploratory and motivational behaviors.Ph.D.Includes bibliographical reference
Hors des cases : Le récit de Soi dans la Bande Dessinée contemporaine des mondes arabes
No full textIn recent decades, adult comics in the Arab world have experienced significant growth. However, the published analyses of these artworks mainly focus on conflicts and trauma.
This dissertation explores a corpus of autobiographical graphic novels and more precisely the relationship between multimediality and the fragmentation of the identity of artists anchored on the edge of the East and the West. Indeed, from Morocco to Lebanon, taboos and censorship persist. These cartoonists are thus determined to promote both their singular Self and their multiple Other. I therefore observe that the fragmentation of identity is transferred to a medium that is just as fragmented and without a fixed form, that the fragile balance of the multiple identity of Arab authors is translated into the fragile balance of a narration using multiple media.
I rely on a close reading of graphic techniques as well as on the impact of transferring and interweaving the comics with other artistic modes. These two approaches highlight how individualization takes the form of a “collective” self. In order to reflect the deconstruction of the graphic genre into the complex sense of identity, my outline details three arguments: the inventory of family heritage, the impact of cartography and History of the place on the artists, and the testimony of an ever-persistent life.
In the first part of the thesis, family memories allow the narrators to present themselves in continuation of this memory. They draw up an inventory of photos, newspapers, postcards, correspondence, etc. They emphasize individual memory as well as daily life and the relevance of the family tree in order to link ancestors and descendants. Also, by developing the idea of an “inter-art,” each artist illustrates the multiple strata of identity.
Then, this family portrait gives way to the portrait of the country which also embraces the different transformations intertwining personal history in the story of great History. The graphic styles construct and deconstruct the borders of these spaces by encouraging the reader to go beyond the page: a place that the cartoonists carry with them and within them.
Finally, the space of the book mirrors the geographical space to express the fragility of memory and above all the need to safeguard today's living spaces which are more important than archaeological sites whose destruction has moved the world. Witnessing the unspeakable in places devastated by conflicts and attacks of all kinds, artists share in a hurry, thanks to social media, the reality of life on the ground. Life changes, but resists.
I realize that these artists come from all backgrounds, but they all refute the social and political constraints of their country. From their thirst for freedom, they offer artworks in their image which fold and unfold, turn and flip back on themselves to represent their multiple.Ph.D.Includes bibliographical reference
Investigating interfacial systems with solid-state nuclear magnetic resonance: characterization of lipids and materials
No full textSolid-state NMR (ssNMR) is a powerful and versatile technique for characterizing a wide range of samples from biomolecules to materials. Solid-state NMR can provide atomic resolution insight into the structure and dynamics of complex systems. This work utilizes solid-state NMR to study lipids and materials.
Lipid bilayers are investigated in chapters 2 and 3. Chapter 2 lays out the ground work for how ssNMR can be used to probe lipids at natural abundance using 31P and 1H. Liposome preparation optimization is also discussed, with sonication being chosen due to the resultant liposome size and longevity. Various lipid compositions are characterized, including liposomes containing phosphatidylserine (PS), which were studied in the presence of calcium. The longevity of the liposomes being studied is shown to be over two years. Studies of the lipid phosphatidylinositol triphosphate (PIP3) are presented, including with 2 mM [Ca2+] present. As intracellular calcium levels are significantly lower, PIP3-containing liposomes at a range of calcium concentrations were prepared and characterized in chapter 3.
This calcium titration of PIP3-containing liposomes with and without PS is the focus of chapter 3. A full assignment of PIP3 by 1H, 31P, and 13C ssNMR is shown. The addition of calcium to PIP3-containing liposomes decreases head group rotational motion for the PIP3 head group phosphates both with and without PS. The formation of PIP3 clusters excludes the lipid phosphatidylcholine, which has increases in head group mobility with an increase in calcium concentration for the highest concentrations. Lateral diffusion decreases are observed via cross polarization kinetics with an increase in calcium concentration for PS and PIP3, with and without PS. The lateral diffusion of phosphatidylcholine only decreases with increased calcium concentration with both PIP3 and PS present, as the anionic lipid clusters are significantly larger.
Solid-state NMR studies of materials are discussed in chapter 4. Drug-loaded polymers were studied due to their different drug release rates. 13C, 1H, and 19F NMR spectra did not show any changes upon drug loading for either polymer, indicating that no chemical interaction was occurring. NMR cryoporometry showed that the pore diameter of the slower releasing polymer was significantly smaller than the faster releasing polymer, making the pores more tortuous and difficult for the drug to leave the pores. Two different metal organic frameworks (MOFs) were also studied. The first, Zn-adtb, separates the linear C6 isomer nHex from other C6 isomers. The C6 isomers were found to reside within the 1D pore system of the MOF and to be highly mobile, indicating that the MOF is acting like a molecular sieve. The second MOF, Zr-tcbpe, was studied for its potential hydrolysis of CS2. A peak corresponding to CO2 was observed growing as the CS2 peak shrunk in intensity. Lead acetate tape tests were performed for proof of hydrolysis, leading to the discovery that the solvent Zr-tcbpe was synthesized in could hydrolyze the CS2 without the MOF present. A search for a set of suitable conditions to test Zr-tcbpe’s CS2 hydrolysis was carried out but was unsuccessful. Other parameters such as crushing the MOF were found to enhance the hydrolysis of CS2.Ph.D.Includes bibliographical reference
Preparation, stability and flavor formation profile of Amadori rearrangement products of glycine, diglycine, triglycine and glucose
No full textAmadori rearrangement products are potential flavor additives with various advantages such as relatively good stability, green production, and the capability of producing fresh and desirable favors, with a good chance to replace traditional unstable flavor constituents, especially the Maillard reaction products (MRPs). Although some research showed that ARPs can serve as promising flavor additives, a lack of systematic investigation is obvious, and more attention needs to be paid to ARPs. Besides, a certain number of amino acid-Amadori rearrangement products (ARPs) have been studied, but there is still a lack of knowledge of oligopeptide-ARPs. Filling the gap should be a great step in the potential usage of ARP as future flavor additives.
This study explored an amenable way to prepare pure ARPs on a large scale with a high yield and found that reducing water content methods worked such as freeze-drying and vacuum dehydration coupled with low-temperature heating. What is more, glycine-, diglycine-, and triglycine-glucose-ARPs were compared for stability and flavor generation in an aqueous system at different temperatures and initial pH values. Oligopeptide-ARPs exhibited relatively weaker stability than amino acid-ARPs. The degradation is positively related to temperature, heating time, and peptide length due to more energy input and more possible bond linkage breakdown sites. Contrastively, oligopeptide-ARPs displayed better flavor formation ability than amino acid-ARPs. ARPs produced similar flavor profiles as MR systems but were capable of producing at lower temperatures, showing easier flavor generation ability than corresponding Maillard systems.
Besides, oligopeptides (diglycine and triglycine) exhibited better relative reactivity of ARP formation than an amino acid (glycine) at relatively low temperatures such as 80 and 100 ℃ and in a wide range of pH from acidic to neutral conditions, but the result reversed at high temperatures for severer instability of oligopeptide-ARPs. The relative reactivity of ARP formation of amino compounds in competing Maillard systems results from dynamic systems with various factors including the chemical characterization and composition of intrinsic reactants, and parameters of matrix conditions like pH, temperature, and thermal treatment time among others.
Overall, ARPs have great potential to serve as food flavor additives, but more research is needed to get a comprehensive understanding.Ph.D.Includes bibliographical reference
Khao I Dang: historical geographies of the UN refugee agency
No full textToday, the Office of the United Nations High Commissioner for Refugees (UNHCR) is a sprawling operational agency with an annual budget of more than $10 billion and a workforce of over eighteen thousand personnel. However, when UNHCR was formed in 1950, it was intended to have a far narrower scope; in contrast to its predecessor, the International Refugee Organization (IRO), it was to be kept strictly “non-operational,” with a limited budget and a small staff dedicated mainly to legal and diplomatic work on international protection issues. On-the-ground operational work—providing material assistance to refugees—was to be left to governments and voluntary agencies, with whom UNHCR would partner in a catalytic and facilitative role. Drawing from oral histories, memoirs, and archival records, this dissertation examines UNHCR’s extraordinary transformation since its founding. First, it reveals a series of interconnected processes through which UNHCR’s pivot to operationalism unfolded, largely within the context of its material assistance programme for Cambodian refugees in Thailand in 1979–82, in the wake of the Vietnam War and Cambodian genocide. Second, it suggests that this assistance programme—particularly the establishment of Khao I Dang refugee camp, which became the central node of UNHCR’s field operation in Thailand—has had a consequential impact on UNHCR’s institutionalization of community development as its primary operational “method.” And, third, it shows how UNHCR’s emergent models of community development were significantly influenced by concepts of neighborhood planning that emerged in the 1910s–20s, ideas and practices of community development that took shape internationally in the 1960s–70s, and forms of self-help and self-governance practiced by refugees in Khao I Dang.Ph.D.Includes bibliographical reference
Social demographic control of a virus using non-pharmaceutical interventions
No full textIn the past few years, the COVID-19 pandemic has caused a significant change in the world. Moreover, there has been a need to develop effective policies to protect the populations quickly. Before introducing the first wave of vaccines in 2021, researchers have worked hard to develop various alternatives to help manage the spread of the disease. Non-pharmaceutical strategies have been employed in this course; they include social distancing, contact tracing, hygiene habits, and isolation strategies, e.g., lockdown and quarantine. With these strategies, there are questions about how their implementation affects the nations considering the strategy. Using systems of differential equations, we can develop epidemiological models which divide the population in compartments, such as the SEIR compartments S - Susceptible, E- Exposed, I- Infected, and R- Removed in this project. We discuss the cost of the pandemic with and without the lockdown strategies. Here we define a cost function that accounts for the economic impact of both the pandemic and the NPI measures. We incorporate social demographic variables into the SEIR model and focusing on developing a aged-based dynamic to understand the impact of NPIs on the population. Utilizing three different scenarios to aid in identifying the most appropriate scenario for implementing the lockdown strategy.M.S.Includes bibliographical reference
Calakmul and Cremona: marriage alliances, war and disaster in historically-independent civilizations
No full textIn this thesis, I explore the similarities between medieval Italian city-states and the Mayan city-states. These two civilizations have no historical connections at all and yet they have many similarities in terms of their political culture. This thesis explores those similarities and also tries to understand why the Mayans and medieval Italians were so similar.The central conclusion is that human nature plus writing creates an impulse for politics that is cross-civilizational and cross-cultural. This leads in many cases to the building of city-states and a focus on the themes of Love (political marriage alliances), Trade, and War. Also, the political regimes that develop in these kinds of city-states are remarkably similar considering the total historical disconnect between the cultures involved.
The general approach and theory behind this thesis is Aristotelian in nature. The idea is that politics is a natural phenomenon waiting to express itself in certain forms, unleashed in large part by writing. Theoretical conceptions of republicanism, human nature, and the city-state are essential elements of this thesis.M.A.Includes bibliographical reference