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A Codrug for Resistant Coinfection: The First Clinically Relevant Antimicrobial-Antiviral Ionic Cocrystal
No full texthttps://rdc.reed.edu/v1/resources/1799be68-638f-4a9f-be0c-82fc634f2b02/thumb/128.jpgAntimicrobial resistance is a primary global health concern predicted to only increase in severity. Without the rapid development of new forms of antibiotics and antivirals, treatments for these infections will become obsolete, endangering lives, minimizing preventative care options, and exacerbating comorbidities. Pharmaceutical cocrystallization is an emerging technology that accelerates drug approval by creating improved solids using FDA approved active pharmaceutical ingredients (APIs). Cocrystals are routinely used to improve the physicochemical properties of drugs but have yet to be explored as a potential alternative to address antibiotic resistance. This work reports the synthesis, characterization, and application of the first clinically relevant drug-drug ionic cocrystal between β-lactamase inhibitor sulbactam and antiviral amantadine. Dual-drug antimicrobial-antiviral cocrystals are exceptionally rare and offer innovative therapy for resistant bacterial-viral coinfections. Single-crystal X-ray diffraction of the ionic cocrystal found lipophilic aggregation and a decrease in empty space within the crystal lattice, suggesting improvements in bioavailability and thermal stability. Susceptibility testing found that the ionic cocrystal presented equivalent and enhanced antimicrobial activity via synergistic interactions between sulbactam and amantadine. Through these findings, this thesis proposes the novel application of pharmaceutical cocrystallization as a sustainable and efficient approach to antimicrobial resistance
Mind's Eye Morality: Mental Imagery, Gender, & Emotion in the Footbridge Problem
No full texthttps://rdc.reed.edu/v1/resources/fbbfde67-4967-475f-a534-d5f69043b5a7/thumb/128.jpgThis study investigated the effects of gender, visualization, and emotion on participant’s moral decision-making. In line with existing literature, we expected that participants would be more likely to choose a deontological response when they had higher visualization and a more negative emotional reaction to a moral dilemma. We also aimed to replicate a finding that participants were less likely to endorse harming a woman in a moral dilemma compared to a man. 225 participants from Prolific read the Footbridge problem where the target to be pushed was either a man, woman, or gender-unidentified stranger. They then reported their emotional reaction, their mental visualization in both a specific and trait measure, and their willingness to push. Results revealed no effect of target gender or visualization on willingness to push. Emotional reaction was positively correlated with willingness to push, but there was no evidence for a mediation role of emotion in accounting for the correlation between visualization and willingness to push
A Man and His Monument: The Creation of the Nixon Presidential Library and the Archival Impact of Richard Nixon's Legacy
No full texthttps://rdc.reed.edu/v1/resources/af42cf65-9d3e-4134-ab9b-110a6d60e248/thumb/128.jpgThe Richard Nixon Presidential Library opened in Yorba Linda, California in 1990, sixteen years after Nixon resigned as President of the United States. The library was Nixon’s passion project and a tool for him to rehabilitate his image and solidify his historical legacy. In 2007, the National Archives and Records Administration (NARA) would take control of the library, ending a decades-long feud between themselves and the former president. But this feud, taking place between 1974-2007, merits further historical consideration. Unlike previous scholarship, this thesis draws a clear connection between Richard Nixon’s post-presidential history and the preservation of presidential history using the creation of the Nixon Presidential Library as a bridge between the two. In this thesis, I argue that, in order to open his presidential library as a monument to himself, Richard Nixon exploited the functions of the National Archives and the Presidential Library system, effectively changing the landscape of presidential historical preservation. I utilize primary materials such as memos, correspondence, fundraising materials, and newspaper articles from the archive at the Nixon Presidential Library in order to support my argument, mainly pulling from collections related to the planning and creation of the library itself
Managing Manganese: The Corporate Duties of MntR in Regulating Metal Ion Homeostasis
No full texthttps://rdc.reed.edu/v1/resources/323166aa-ca78-454a-8b8a-8482e05104f0/thumb/128.jpgManganese homeostasis is essential for bacterial virulence. Manganese transcription regulator (MntR) from Bacillus subtilis controls the transcription of both Mn+2 importers (MntH and MntABCD) and exporters (MneP and MneS), and the molecular mechanism for this delicate dual control is of great interest. Each monomer of MntR (142 residues, 16.7 kDa) binds two Mn+2, which greatly increases its affinity for DNA. It has been shown that MntR binds cooperatively to four binding sites upstream of the transcription start site to induce the expression of manganese efflux transporters. Furthermore, the first MntR binding site overlaps with the RNA Polymerase recognition sequence, suggesting that some interaction between these two proteins likely contributes to the specified activation of MneP expression by MntR. To better understand both cooperative binding and transcriptional activation, three mutations were made to highly conserved residues in MntR. These mutations aimed to disrupt intra-dimer stability, inter-dimer coordination, and MntR:DNA complexation. Mass photometry was used to investigate the oligomeric state of the assembled complexes, consisting of (mutant or wild type) MntR and a DNA duplex containing four MntR binding sites. Preliminary data suggest that inter-dimer and MntR:DNA contacts are essential for a 4 MntR:1 DNA complex to form, and this is the most stable minimum oligomer state for this complex. Future investigations should aim to study complex formation between MntR, RNA Polymerase, an adjoining sigma factor, and a DNA duplex containing the RNA Polymerase binding site and transcription start site, in addition to the four MntR binding sites. These studies should seek to identify possible oligomeric states, using both mass photometry and cryo-EM as possible techniques. This will help further elucidate the mechanism of transcriptional activation by MntR
Comparing the Production of Word Final Devoicing in German and English
No full texthttps://rdc.reed.edu/v1/resources/3a8520b0-1565-4e7d-8f80-081e2c2efb5c/thumb/128.jpgIn this thesis, I investigate the neutralization of word-final consonant devoicing in German by both English and German speakers. I examine the use of preceding vowel duration, stop closure duration, voicing into closure, and F1 offset frequency by English and German speakers. I also use an EGG to investigate use of creaky voice before word-final consonants. I found that German speakers had higher open quotient before underlyingly voiceless consonants in German, and also had higher F1 offset frequency before underlyingly voiceless consonants. I also found that for some speakers voicing into closure was correlated with stop closure duration
Mixed Signals: A Game-Based Analysis of the Signal Protocol in the Presence of Active Adversaries
No full texthttps://rdc.reed.edu/v1/resources/99b91954-24e6-49e5-87d2-dc2236ecd95c/thumb/128.jpgInstant messaging is an integral part of online communication, and it has received a deal of attention from advocates desiring stronger security in the past decade. Services began implementing end-to-end encryption, and secure protocols began popping up. Of particular fame is the Signal protocol, which uses a double-ratchet to not only provide end-to-end encryption, but to provide protection even when a user is compromised. In this work, we study the security guarantees provided by the Signal protocol in the presence of adversaries which inject messages after corrupting user state, showing that the security properties of Signal still apply to most such attacks, and that a slightly modified version of the protocol can detect an adversary which injects a certain type of ciphertext
Sparse theorems are full of triangles
No full texthttps://rdc.reed.edu/v1/resources/034b5256-887e-4fc2-a245-c98536ff27a8/thumb/128.jpg"Classical planar geometry is rife with theorems. Even in the highly restricted setting of ``straightedge geometry'', the theorems are so abundant and apparently ad hoc that it seems impossible to understand every possible theorem. In this thesis we develop techniques for recognizing theorems from the purely combinatorial data describing the construction of the theorem. Naturally this approach is limited since different theorems hold in different models of planar geometry, but we show that, contrary to expectations, much of the structure of theorems can be determined from this combinatorial data alone. Our techniques lead to the identification of an elegant property of theorems that hold in some projective plane over an infinite field: ``partial triangles'' in the diagram describing a theorem are typically filled in by full triangles. We call this the horn-filling property by analogy with abstract homotopy theory. Although we develop our theoretical framework in the context of general theorems, the theory as currently developed is not powerful enough to be effective without stronger hypotheses. We focus primarily on theorems whose diagram forms a 3-configuration, which is the simplest non-trivial class of diagrams in which theorems arise. In this case we prove the horn-filling property holds for every partial triangle in a theorem. Furthermore, this property almost characterizes the theorems: the only 3-configurations with the horn-filling property are the Fano, M\""obius-Kantor, Pappus, and Desargues configurations. Among this list only the M\""obius-Kantor configuration fails to be a theorem over some infinite field; our techniques can also be used to explain the exceptional behavior of the M\""obius-Kantor configuration.
The Cobordism Hypothesis and Topological Quantum Field Theories
No full texthttps://rdc.reed.edu/v1/resources/aaa358b2-8fb8-4f9c-ac6c-0125b761d9b9/thumb/128.jpgThis thesis explores the theory of cobordism and topological quantum field theories. We develop the requisite machinery to state the cobordism hypothesis
State SNAP Policy: Enrollment, Poverty and Food Security
No full texthttps://rdc.reed.edu/v1/resources/095c916e-a8d7-4489-b499-c47698d83784/thumb/128.jpgSince 1996, states have changed the way they administer the Supplemental Nutritional Assistance Program (SNAP). These policy differences can directly affect who is eligible for the program, minimize the transaction costs for receiving SNAP benefits or affect the stigma of applying for and receiving benefits. I construct a panel data set to analyze state SNAP policy variations, SNAP enrollment, state poverty rates, and state food security rates from 1996 to 2016. I find that if a state adopts a more generous eligibility policy, there is a large impact on the percentage of the state's population enrolled in SNAP, though these policies do not appear to have an effect on poverty or food security. I also find that SNAP outreach spending in a state has strong effects on SNAP enrollment in the state, and states with higher poverty are more likely to increase SNAP outreach spending. I do not find any state SNAP policy that affects food security rates
Analyzing the Impact of Userspace Bypass on the Performance of the Spectre Attack
No full texthttps://rdc.reed.edu/v1/resources/312bd521-0ffa-4fdb-b8c0-1033ee33917e/thumb/128.jpgThis thesis investigates the impact on a system’s security concerning the spectre attack when running userspace bypass. To do this background will be provided on both userspace bypass and the spectre attack and the necessary concepts to understand them. This paper is focused on the first variant of the spectre attack side channel attack which uses changes in the cache state and speculative execution to get around memory security and read what should be protected data. Userspace bypass is a scheme that aims to increase performance by alleviating the overhead with high densities of system calls. It does this by allowing programs to bypass the operating system and perform the system call themselves. This paper aims to investigate if there is an impact on the security of a system, specifically against the spectre side channel attack, while running userspace bypass. To test this the spectre attack was run on a system using userspace bypass, both for when the program was bypassed and when it was not. The results of the tests were then compared to the results from a known vulnerable system provided by the spectre attack’s original paper. The data collected would indicate that for that version of the operating system that was running userspace bypass there was no impact on the performance of the attack. From this conjecture is proposed that userspace bypass does not impact the security of the system in terms of the spectre attack