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Crushing It: Inquiry At the Crossroads of Topology Optimization and Machine Learning for Dynamic Properties of Architected Material Unit Cells
No full textAdditive manufacturing has dramatically expanded the design space for structural components. New designs, impossible to manufacture conventionally, have material properties not seen in nature, including improved strength-to-weight ratios and superior energy absorption capacity. Herein, we investigate the class of additively manufactured materials composed of repeating substructures, known as architected materials or metamaterials. The optimal design of these component structures, called unit cells, touches on the field of topology optimization, which utilizes iterative mathematical analysis to produce a design with targeted properties. This work is an application of machine learning for topology optimization of unit cells.
The first chapter presents a dataset of voxelated unit cell topologies and their accompanying material properties. We generated hundreds of designs in sets with varying volume fractions, then computed their properties for multiple physics – mechanics (stiffness, etc.), thermal conductivity, and fluid permeability. This dataset serves as the training data for machine learning models. Next, we apply convolutional neural networks (CNNs) to the unit cells represented as three-dimensional binary arrays to predict their properties. A trained model consumes far less time to predict these properties than do finite element methods – especially for three physics; this model could save significant time by supplant FEA in the conventional TO method. Subsequently, we explore graph representation of the topologies, which allows for application of graph neural networks for property prediction. This inquiry into graph data representation was enriching, if unsuccessful.
Next, we develop variational autoencoders to produce synthetic data for dataset augmentation and optimization of unit cells for behavior under high strain-rate compression. We engineer ML features from a small set of results from dynamic event simulations and link those to the multi-physics dataset using linear regression, enabling us to use the larger dataset for machine learning-topology optimization. Our workflow’s results validate the approach, offer room for improvement, and compose a basis for further inquiry. The final chapter details our foray into physics-informed machine learning, which uses physics domain information and neural networks for learning nonlinear relationships. We applied this to learning and generating stress-strain curves for dynamic dataset augmentation. While unsuccessful, the model development process was extremely enriching
EMERGENCE AND EPIDEMIOLOGY OF MPOX IN THE UNITED STATES: LESSONS LEARNED AND IMPLICATIONS FOR FUTURE STRATEGIES
No full textThe overarching goal of this study was to assess the factors associated with mpox beliefs, stigma, and vaccination in the United States (U.S.) to identify lessons learned to apply to future mpox response strategies. Specially, we aimed to 1. Describe knowledge and beliefs about mpox; 2. Develop measures to evaluate impacts of mpox-related stigma; 3. Evaluate factors related to mpox vaccination.
Since May 2022, mpox was declared a public health emergency of international concern with mpox being confirmed in 117 countries/territories. Due to its widespread incidence, its threat of endemicity or re-emerging outbreaks is significant. There is a growing but scarce body of literature related to mpox, with many unanswered questions related to disparities and factors associated with vaccination, and stigma and how this will change in the coming years. Furthermore, the emergence of COVID-19 and mpox have influenced accessibility of sexual health services and public perception of infectious diseases, which could be leveraged to inform public health responses for the future of mpox and other infectious disease threats.
Data were collected among men who lived in the United States between 2022-2024 and participated in the American Men’s Internet Survey (AMIS). This study was a rapid response to the mpox epidemic using a national survey to address unsolved questions in the public health response. These data allow for assessment of contextual effects through developing consistent metrics. This research aims to characterize factors associated with mpox knowledge, stigma, and vaccination, among the group at highest risk in the U.S. during 2022-2024: gay, bisexual, and other men who have sex with men (GBMSM). Describing the complex factors (individual, network, community, public policy, and epidemic stage) that influence disease spread is essential to public health, the wellbeing of populations, and to prepare for future rapidly moving infectious disease epidemics
CLONIDINE-MEDIATED CELL CYCLE RE-ENTRY AND METABOLIC REPROGRAMMING IN HIPSC-DERIVED CARDIOMYOCYTES
No full textBackground: Owing to the poor regenerative potential of the adult human heart, cardiomyocyte (CM) loss following myocardial infarction is a major contributor to progressive cardiac dysfunction. Clonidine, a clinically approved α2-adrenergic agonist, has been previously implicated in promoting CM cell cycle re-entry; however, its mechanisms have yet to be defined. This study investigated the proliferative and metabolic effects of clonidine in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered heart tissues (EHTs).
Methods: Live cell cycle imaging was conducted using a PIP-FUCCI adenoviral construct to monitor changes in cell cycle dynamics following clonidine treatment. Mitochondrial function was evaluated through Seahorse XF mitochondrial stress testing, while a phospho-kinase array was used to identify activated signaling pathways. Lastly, functional outcomes were measured in 3D EHTs by quantifying spontaneous contraction force, frequency, and qualitative PIP-FUCCI expression.
Results: In this study, we found that clonidine induced a dose- and time-dependent increase in CM cell cycle re-entry as evidenced by a shift from G1 to G2/M phases. Interestingly, mitochondrial respiration also increased in a dose-dependent manner, resulting in a significant increase in basal, maximal, and ATP-linked oxygen consumption. The cell cycle and metabolic-induced changes correlated with activation of the Akt–mTOR, RSK–CREB, and JAK–STAT3 pathways. Despite enhanced mitochondrial metabolism, clonidine did not improve contractile force in EHTs; however, it significantly reduced EHT contraction frequency, which is consistent with its known chronotropic effects. Qualitative analysis of PIP-FUCCI expressing EHTs revealed similar effects to 2D models, whereby clonidine enhanced S/G2/M phase expression.
Conclusion: These findings indicate that clonidine promotes hiPSC-CM cell cycle re-entry and enhances mitochondrial oxidative metabolism through activation of key proliferative and metabolic signaling pathways. These results provide a foundation for future studies aimed at optimizing combinatorial strategies for cardiac regeneration
Evaluation of Simplify Writing in St. John Nepomucene School: A Case Study
Get PDFThe purpose of the present case study was to examine the first year of implementation of Simplify Writing in a small elementary school setting. To address the primary research questions, CRRE employed multiple qualitative measures of stakeholder perceptions, satisfaction, and experiences. The results of a 1.5-day site visit indicated that teachers were following the prescribed program implementation in duration and frequency. Teachers found online training had adequately prepared them for implementation, although all would prefer in-person training. Major instructional strategies observed included modeling, use of graphic organizers, active engagement, and teacher feedback. Each of these strategies were noted to be implemented with consistency across grade levels.
Teachers cited an increase in students’ interest and motivation in writing this year, and attributed that to the program, which provides clear lesson plans and incorporates consistent language across grade levels. Many teachers conveyed that their enthusiasm for the program translated into providing more verbal praise for their students’ writing which, in turn, helped to increase student confidence. Students, especially those who had a book published with their classmates, were excited to learn more about the writing process and express themselves more creatively. Parents noted their students’ excitement when sharing their written work at home.
Overall, teachers were enthusiastic about having a writing curriculum that was well organized, easy to implement, and provided useful resources. Their excitement was evident in that they are already looking forward to next year when students will be experienced with the curriculum which, hopefully, will translate into even more improved writing outcomes. With a few modifications, and the opportunity for in-person professional development, even more successful implementation is promising in the future
EVALUATING THE ROLE OF GENES TB927.7.4060 AND TB927.7.4070 INVOLVED IN TRYPANOSOMA BRUCEI PATHOGENESIS
Get PDFTrypanosoma brucei is a protozoan parasite that poses a significant threat to human and animal health in sub-Saharan Africa. While traditionally considered a bloodstream parasite, increasing evidence suggests that T. brucei can invade extravascular spaces within tissues, leading to inflammation, organ damage, and immune modulation. Recent studies have demonstrated that T. brucei colonizes the heart, where it induces myocarditis and cardiac dysfunction. However, the mechanisms underlying host-pathogen interactions in this environment remain largely unexplored. Previously, transcriptomic analysis was performed, revealing that intracardiac T. brucei populations exhibit distinct gene expression profiles compared to intravascular parasites. Among the differentially expressed genes, we identified Tb927.7.4060 and Tb927.7.4070, initially hypothesizing that they were involved in cardiac colonization. However, further analysis revealed that these genes play a broader role in T. brucei pathogenesis.
In this study, we determined that Tb927.7.4060 and Tb927.7.4070 encode proteins localized on the parasite surface, with strong enrichment along the flagellum. This localization suggests their potential involvement in membrane trafficking and flagellar-associated processes. To further explore their function, we generated double-knockout parasites using CRISPR-Cas9 and assessed their impact on antibody clearance. Antibody clearance assays demonstrated that knockout parasites exhibited a significantly lower surface-bound antibody removal rate compared to wild-type parasites, suggesting that Tb927.7.4060 and Tb927.7.4070 contribute to efficient antibody endocytosis. Despite this defect, the knockout parasites did not show growth abnormalities in vitro.
Our findings provide new insights into the molecular mechanisms of T. brucei pathogenesis, particularly in immune evasion and flagellar function. More research is needed to elucidate the precise roles of Tb927.7.4060 and Tb927.7.4070 in facilitating tissue invasion and persistence
The Impact of Artificial Intelligence on the Deliberate Biological Threat Landscape
Get PDFTechnology plays a critical role in society, driving advancements that have led to lifesaving vaccines, nuclear power, and space exploration. These innovations have changed the day-to-day lives of people worldwide. However, the same technologies can be misused to pose catastrophic threats to humanity and to cause other societal and individual harms. They can facilitate the spread of disinformation, generate malicious content, and contribute to the development of conventional and unconventional weapons. Such technologies are known as being “dual-use” because they can be used for beneficial and malevolent applications. They are therefore subject to the “dual-use dilemma”, a situation in which it is difficult to prevent the misuse of a technology without limiting its benefits. The convergence of artificial intelligence and the life sciences represents the coupling of two dual-use technologies to achieve new scientific capabilities.
This dissertation explores key aspects of the governance of artificial intelligence in the life sciences with the perspective that policy is one method of risk mitigation. It analyzes the impact of artificial intelligence on mail-order DNA synthesis biosecurity measures and presents a novel framework for characterizing the impact of artificial intelligence on biological risk. Additionally, it reports on virologist perspectives from semi-structured interviews about the risks and benefits of artificial intelligence and on the development of practical policy. It concludes by discussing the current landscape around artificial intelligence and biosecurity, noting the great uncertainty of the federal government’s role in the future
Assessing Nerve Degeneration with Quantitative Optical Coherence Tomography
No full textPeripheral nerve degeneration, particularly Wallerian degeneration, significantly affects functional recovery following nerve injury. However, current diagnostic tools such as electromyography (EMG), MRI, and ultrasound provide limited resolution or quantitative information about axonal myelination and structural integrity. This thesis explores the use of attenuation-based quantitative optical coherence tomography (qOCT) as a non-invasive tool for assessing peripheral nerve health. By imaging both mouse sciatic nerves (in vivo and ex vivo) at various stages post-injury as well as swine forelimb nerves (ex vivo), we evaluated structural and optical differences between healthy and degenerative nerves. OCT imaging revealed that degenerative nerves exhibit reduced attenuation coefficients and loss of periodic banding structures known as the Bands of Fontana, which correlate with underlying myelin degradation. Quantitative attenuation-based analysis using frequency-domain (FD) and depth-resolved attenuation (DRA) methods demonstrated statistically significant differences in optical properties between control and degenerative nerves, supporting the diagnostic potential of qOCT. Beyond OCT, this thesis also summarizes a separate project on developing a compact, focus-tunable two-photon (2P) fiberscope for three-dimensional (3D) neuronal imaging, enabling depth scanning without mechanical movement. Together, these studies underscore the utility of advanced optical imaging for both clinical and research applications in nerve injury assessment and functional imaging
THE OPPORTUNITIES AND CHALLENGES OF MEETING RAPIDLY GROWING DATA CENTER ENERGY DEMAND: POLICY CONSIDERATIONS IN THE U.S.
Get PDFBehind the growth in use of artificial intelligence (AI) related systems is a large and complex discussion about how to meet the growing energy demand of AI data centers.The purpose of this research is to outline the challenges and opportunities for the electric industry to address data center growth while maintaining affordability and meeting emissions reductions goals. The study included a brief overview of activities at the federal level through the Federal Energy Regulatory Commission (FERC) and a review of three state case studies: Indiana, Texas, and Virginia.
While the three states studied in this report are at very different stages within their data center deployment, key policies being considered in all three states include changes to data center tariffs and consumer protections. At the federal level, FERC’s decisions on co-location issues will greatly inform how data centers, generation owners, and state policymakers can move forward. However, based on these examples, the policies and regulations currently in place and being considered by policymakers are likely inadequate to fully address the growing energy needs forecasted to meet data center growth
From Possessed, Witch, to Madwoman: Internment and Devotion at the Salpêtrière Asylum through the Letters of an “Imprisoned” Mystic, Louise du Néant
Get PDFThe History MA Thesis centers on the first edition hagiographical text of a little-known seventeenth-century French lay mystic, Sœur Louise, through her text: The Triumph of Poverty and Humiliations or the Life of Mademoiselle De Bellere du Tronchay, Commonly Called Sœur Louise: With her Letters. The vita and other foundational sources for this research were found within the Women of the Book Collection at Johns Hopkins University. Her text, published in Paris in 1732, is half a vita written by her last confessor, Jean Maillard a Jesuit mystic, and half a collection of 52 letters she wrote to her confessor Jean Briard from 1679 to 1684, and her last confessor Jean Maillard from 1684 until her death in 1694. Through an analysis of the text as a whole, considering the multiple voices of confessors and Sœur Louise, this thesis aims to understand her unique lived experiences as a holy woman who was “imprisoned” and shut in at the Salpêtrière asylum, and argues that she transformed her confinement into spiritual labor for God and others.
The thesis analyzes the holy and heretical groups and institutions her life was intertwined with including the Salpêtrière and religious orders, takes seriously her intense mystical devotion and emotions through methodologies and theories within the history of religion, and considers the societal and cultural understandings of witchcraft and madness of which she was accused of both – all of which led her to being shut in at the Salpêtrière. Her choice to stay at the Salpêtrière, even though she was discharged by her first confessor is argued as peculiar as the thesis explores what life looked like in this hospital, asylum, and prison. A historical contextualization of her life during the Jansenist controversy, and when her book was published during the rise of the Convulsionnaires, reveals throughout the thesis how even the life of a little known lay mystical woman was impacted by greater political and religious contestation
Assessing prelamin A processing and phenotypic effects of LMNA mutations in a residue adjacent to the ZMPSTE24 cleavage site
Get PDFLamin A is a nuclear scaffold protein, synthesized as a precursor called prelamin A, which undergoes several steps of posttranslational processing. This study explores the impact of mutations that affect the final proteolytic processing step, which is mediated by the zinc metalloprotease ZMPSTE24. We assessed the effects of these LMNA mutations, specifically at the L647 residue, on nuclear morphology and protein processing. After establishing a HeLa T-REx cell culture system, we expressed wild-type GFP-tagged LMNA and 11 GFP-tagged LMNA mutants. These mutations were examined against the abnormalities seen in cells from patients with Hutchinson-Gilford Progeria Syndrome (HGPS) and other disorders characterized by the accumulation of unprocessed prelamin A. Results in mammalian cells were compared to previous work performed in a humanized yeast system. Our findings indicate that diminished processing of prelamin seen in the yeast system is recapitulated in mammalian cells. Our results also indicate significant nuclear morphological abnormalities. However, there were no specific correlations between mutations with low cleavage efficiency and higher abnormal nuclei count. This research marks a significant step in understanding the impact of mutations at L647 in prelamin A processing and associated cellular defects. Overall, this study lays the foundation for future investigations into understanding the molecular mechanisms of how LMNA mutations may result in diseases