Geotransformación and Overcoming Underdevelopment in Socialist Cuba

The term geotransformación, coined and theorized by Cuban geographer and revolutionary Antonio Núñez Jiménez in his 1968 book Geotransformación de Cuba, is an analytic frame which emphasizes the interconnectedness of social and natural transformation. As such, geotransformación functions as a conceptual weapon against not only theories of geographic determinism attempting to depoliticize history, but also grand historical narratives which center the human by overstating its independence from the forces of nature. Taking geotransformación as a conceptual compass for a return to the Cuban Revolution’s decisive early years, I engage in close readings of primary texts including geographic treatises, legal documents, and poetry. Drawing on key passages from Geotransformación de Cuba, I argue that agrarian reform cannot be separated from the social transformations of the revolution. Then, I theorize the plantation as an engine of underdevelopment and show how overcoming the structure of the colonial plantation formed the central task of agrarian reform. An analysis of Hurricane Flora and Cuba’s response to its devastation highlights the importance of geotransformación’s conceptual frame for understanding the interconnections between social and natural transformations in Cuba, and how these transformations relate to overcoming the long history of Cuba’s underdevelopment. I conclude by arguing geotransformación forms an important contribution to the wave of ecological thought which emerged in Marxist theory beginning the 1960s

Bridging the Gap Between Molecular Components and Functional Electronic Chemical Sensing Devices with 2D Layered, Conductive Metal–Organic Frameworks

Layered, conductive framework materials are a class of materials with properties that make them ideal sensing materials in electronic chemical sensors. My thesis is focused on the development of these materials for electrochemical sensing of liquid phase analytes, and on understanding the material–analyte and material–electrode interfaces, and their self-assembly and deposition onto surfaces. Chapter 1 provides a summary of the use of layered conductive metal–organic frameworks (MOFs) and covalent organic frameworks (COFs) in electronic chemical sensors, detailing the materials and sensor architectures employed, and the analytes detected. Relevant performance metrics are compared, and investigations into material–analyte interactions are highlighted. Chapter 2 investigates the use of hexahydroxytriphenylene-based MOFs as the working electrode material for voltammetric detection of nitric oxide, comparing the impact of the metal node on electrode sensitivity to NO. A nickel-based material showed sensitivity to NO, but displayed limited stability on a glassy carbon substrate, which was improved by employing a conductive polymer adhesive, highlighting the impact of the MOF-electrode interface on sensing performance. Optimized electrodes detected NO at nanomolar concentrations and exhibited moderate selectivity against potential interferents. Chapter 3 describes the investigation into the self-assembly of Ni3(HHTP)2, a layered conductive MOF. A novel method for monitoring MOF deposition with ATR-FTIR was developed to study the impact of oxidants on the rate of MOF formation. The presence of oxidants impacted the crystallinity and morphology of the resulting MOF particles, with oxidant-free conditions inhibiting MOF formation, and excesses of oxidant resulting in irregularly shaped particles. The initial phase of Ni3(HHTP)2 self-assembly was identified as the formation of Ni-HHTP coordination complexes in solution, which then assembled into crystalline MOF with the addition of oxidant. The appendices provide preliminary data that highlight promising future directions: that of exploring phthalocyanine-based frameworks for NO sensing (Appendix A), and that of depositing MOFs onto threads for flexible sensors (Appendix B). Taken together, the chapters of my thesis provide new understanding of the molecular interactions by which layered conductive MOFs self-assemble, adhere to substrates, and interact with analytes, which lays the groundwork for employing these materials in a variety of biosensing applications

Microglial Dynamics and Mechanisms Underlying the Phagocytosis of Dying Oligodendrocytes

Myelin is a complex multilamellar structure, generated by oligodendrocytes, that ensheaths axons and is a vital component for neural processing. Degeneration of both oligodendrocytes and their myelin sheaths is a common pathological feature associated with aging and neurodegenerative diseases. Efficient removal of the cellular and myelin debris is crucial for remyelination and prevention of further degeneration. Microglia, the primary phagocytes of the CNS, are thought to play a key role in this process. To investigate the cellular dynamics underlying microglia-mediated clearance of degenerating oligodendrocytes and myelin sheaths, at the single cell level, we developed a novel model for inducible cortical demyelination called oligodendrocyte 2Phatal. This model activates a non-inflammatory stereotyped degeneration cascade, leading to remyelination by local oligodendrocyte precursor cells. Using this model of single-cell demyelination, I observed microglia engaging with both the targeted oligodendrocyte and its myelin sheaths followed by a stereotyped and efficient removal of both. Following the removal of the myelin sheath, I observed rapid remyelination, suggesting that efficient clearance of the myelin debris plays a vital role in successful remyelination. Deletion of the fractalkine receptor, CX3CR1, delayed microglia engagement with the targeted oligodendrocyte but did not affect the clearance of myelin sheaths. Surprisingly, the deletion of the phosphatidylserine receptor, MERTK, had no impact on the clearance of either the targeted oligodendrocyte or the myelin sheaths. These new findings reveal the underlying cellular dynamics involved in myelin debris clearance and repair and highlight the role of CX3CR1 signaling in the efficient removal of dying oligodendrocytes

Reading in the Margins: Cosmopolitan Women Readers in Sijie Dai’s Balzac and the Little Chinese Seamstress and Yoko Tawada’s “Persona”

This paper examines two pieces of fiction that foregrounds an Asian woman’s reading of western literature, Balzac and the Little Chinese Seamstress (2000) by Chinese-French writer Sijie Dai and “Persona” (1993) by Japanese-German writer Yoko Tawada. These female readers are positioned on an overdetermined “margin”: their femininity defines them as either wanting of cultural enlightenment or inadequate to engage with the canon; their foreignness renders the reading process to be either superficial or torturing; however, it is also this marginal position that constitutes a unique approach to building their world through literature, that is, a perspective that neither align them with the imperialist ideology, nor confine them to a national consciousness. This paper provides a countering framework of reading-as-worlding against orientalism from the perspective of East Asian women–how they develop their own sense of cosmopolitanism via engagement with foreign literature and how they modify and uphold this sense of cosmopolitanism in the increasingly globalized space. By putting these two texts together, I want to pinpoint the act of reading as an encounter with the cultural other, which insufficiently illuminates the knowledge of the other, yet heuristically leads towards an exploration into one’s self

Targeting Aspergillus fumigatus hypoxia response pathways for novel antifungal drug development.

Invasive fungal disease present are difficult to diagnose and treat and present a high mortality rate across the world with approximately 1.5 million people a year succumbing to fungal infections worldwide. Currently, there are limited antifungal classes used therapeutically, and antifungal drug resistance on the rise further exacerbates the dire need for novel therapeutics with innovative mode of actions. The filamentous fungi, Aspergillus fumigatus is the causative agent of invasive pulmonary aspergillosis (IPA). It is estimated that contemporary antifungals fail in about 50% of patients with invasive filamentous fungal infections, likely due to the biofilm mode of growth exhibited in vivo by filamentous fungi. In vitro, we have shown that as biofilms mature, the establishment of low oxygen microenvironments directly contributes to their increased antifungal resistance. The transcription factor SrbA, is essential for adaptation to low oxygen, biofilm formation, virulence, and azole resistance. Therefore, we postulated inhibition of SrbA as a potential novel therapeutic strategy to combat invasive filamentous fungal infections and azole resistance. In this dissertation we describe a high-throughput screen to identify SrbA pathway inhibitors and further characterize the mode of action of two of the small molecule hits, MBX-7591 and MBX-7498. Both of these molecules show synergy with azoles and decrease total oleic acid content, which alters phospholipid composition. Furthermore, MBX-7591 is effective in vivo in decreasing fungal burden against A. fumigatus and R. delemar. Additionally, in this discussion we additionally studied the predicted sterol transporter ArvA in A. fumigatus and identified a putative role in the conidial transition from isotropic to polarized growth and cell wall composition

Healthcare utilization associated with mental health symptoms in young adults with type 1 diabetes

Today, as mental health illnesses such as depression, anxiety, and eating disorders continue to expand, they are further associated with poor glycemic control, decreased quality of life, increased unemployment, and worse self-care. This study aims to describe the relationship between psychological and diabetes distress and emergency healthcare utilization including 911 calls, ED visits, and hospitalizations among young adults with T1D. The collected and analyzed data indicate that T1D-related ED visits and hospitalizations are significantly associated with higher levels of mental health symptoms and diabetes distress in young adults. In contrast, no significant relationships were found between T1D-related 911 calls and mental health symptoms or diabetes distress.https://digitalcommons.dartmouth.edu/wetterhahn_2024/1004/thumbnail.jp

Regulation of Lipid Composition of the Golgi during Tissue Formation: Where Does PI 4-Kinase Stand?

Four Wheel Drive (Fwd), the Drosophila homologue of PI 4-kinase IIIβ, is a conserved phosphatidylinositol 4-kinase (PI4K) that localizes to the Golgi apparatus and functions in protein trafficking from the Golgi to the plasma membrane. The goal of this project was to determine how the localization of Fwd to the Golgi is regulated during early embryogenesis in Drosophila. Our initial observations suggested that Fwd was only localized to a subset of Golgi apparatus, raising the question of whether distinct types of Golgi apparatus exist in early Drosophila embryos. By optimizing imaging conditions, we found that many Golgi compartments initially identified as Fwd-negative showed weak Fwd-GFP signals, arguing against the existence of a sub-population of Golgi that completely lack Fwd. In addition, we found that phosphatidylinositol 4-phosphate (PI4P), the lipid product of PI4Ks, were both strongly enriched on the plasma membrane and weakly associated with intracellular puncta-like structures. These intracellular signals appear to overlap with Fwd-GFP, suggesting that Fwd colocalizes with its lipid product on the Golgi apparatuses. Together, our findings demonstrate that Golgi apparatuses differ in their capacity to recruit Fwd, which may impact their rate of PI4P production. These observations raise the question of how the activity of individual Golgi apparatuses are regulated in developing tissues.https://digitalcommons.dartmouth.edu/wetterhahn_2024/1003/thumbnail.jp

Formation of new cohesive linkages and regulation of cohesion rejuvenation during meiotic prophase in Drosophila oocytes

During meiosis, faithful segregation of chromosomes requires maintenance of sister chromatid cohesion from premeiotic S phase until its stepwise dissolution at anaphase I and anaphase II. Research in humans and model organisms indicates that premature loss of meiotic cohesion is a major determinant of age-induced aneuploidy in human oocytes, a phenomenon known as the maternal age effect. Because cohesin turnover after S phase has not been detected in mice oocytes, the prevailing model for mammalian oocytes is that cohesion cannot be replenished after its initial establishment in S phase. However, previous research from the Bickel lab suggested that a cohesion rejuvenation program operates in Drosophila oocytes to maintain sister chromatid cohesion during meiotic prophase by generating new cohesive linkages. This dissertation presents the first evidence that cohesin expressed during meiotic prophase is used to form new cohesive linkages as part of a cohesion rejuvenation program. In addition, my work demonstrates that, as a result of extensive cohesin turnover, cohesin along the chromosome arms can be completely replaced multiple times during meiotic prophase in Drosophila oocytes. Furthermore, cohesin loading on chromosome arms is facilitated by the cohesin loader Nipped-B, and lack of cohesin loading during meiotic prophase results in premature cohesion loss. To identify factors specifically involved in cohesion rejuvenation during meiotic prophase and not S phase establishment, I performed a genetic screen and identified 29 proteins that are required during meiotic prophase for accurate chromosome segregation in Drosophila oocytes. Further investigation of two positive hits revealed that Brahma and Pumilio are essential for maintenance of arm cohesion during meiotic prophase, potentially by regulating Nipped-B-dependent cohesin loading. The work presented here describes a validated approach to identify proteins specific to the prophase rejuvenation pathway and provides new insight into the mechanisms governing rejuvenation of meiotic cohesion in oocytes. Findings in this dissertation have the potential to advance our understanding of the mechanisms underlying cohesion maintenance during the prolonged meiotic prophase in human oocytes and defects that lead to the maternal age effect

Shader-based Real-time Image Tracking for Mobile Augmented Reality

Image target tracking is a technique widely used in a variety of augmented reality (AR) applications to trigger AR interaction and accurately locate virtual objects relative to physical space. This project is a Unity image tracking pipeline based on the ORB feature detection and description technique that seeks to be robust enough to track images despite partial occlusion, uneven lighting, and image target depth. This pipeline employs compute shader code to conduct image tracking computations on the GPU to track images in real-time for mobile AR apps