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[Maine SUD] Drug Supply Insights and Falling Overdose Rates
No full textKeynote presentation at Maine Substance Use Disorder Learning Communit
The Accuracy of ChatGPT in Answering FAQs, Making Clinical Recommendations, and Categorizing Patient Symptoms: A Literature Review
Get PDFBackground ChatGPT is a popular open-source large language model (LLM) that uses supervised learning to create human-like queries. In recent years, ChatGPT has generated excitement in the medical field. However, its accuracy must be carefully evaluated to determine its usefulness in patient care. In this literature review, the authors examine whether ChatGPT can accurately answer frequently asked questions (FAQs) from patients, make clinical recommendations, and effectively categorize patient symptoms. Methods A database search in PubMed was conducted using the search terms “ChatGPT,” “accuracy,” and “clinical decision-making,” yielding 122 unique references. Two screening stages resulted in 9 studies that met the evaluation criteria for this review. Results Analysis of 9 studies showed that while ChatGPT can answer FAQs, offer recommendations, and categorize symptoms in less complicated scenarios, its clinical accuracy ranged from 20% to 95%. ChatGPT may be helpful in specific clinical scenarios; however, its variable accuracy makes it unsuitable as a stand-alone point-of-care product. Conclusions ChatGPT is only adept at providing generalized recommendations when individual patient care is more suitable. Further research is needed to identify where ChatGPT delivers the most accurate responses and how it can supplement traditional care
THEME AND VARIATIONS OF SALT AND SHAPE: INVESTIGATING INFLUENCES OF SEPTIN ASSEMBLY IN MULTIPLE YEAST SPECIES
Get PDFSeptins are a conserved family of GTP-binding proteins that assemble into filaments and play critical roles in cellular organization and morphogenesis. Understanding their polymerization mechanisms is essential for elucidating how cells spatially and temporally regulate their assembly. In this thesis, we investigated the intrinsic polymerization modes of septins and the influence of electrostatic interactions and membrane geometry on their assembly. Our results reveal that septin polymerization exhibits hallmarks of cooperative assembly, with a strong dependence on salt concentration and membrane binding. We demonstrate that increasing ionic strength modulates the polymerization mode, assembly rate, and critical concentration, underscoring the sensitivity of septin dynamics to electrostatic conditions. Furthermore, we find that septins preferentially bind to curved membranes, which enhances membrane engagement and influences polymerization behavior compared to planar membranes. While cooperative assembly dominates in solution, septin behavior on membranes suggests a transition to more isodesmic-like polymerization, potentially due to altered conformational constraints or competitive binding interactions. These findings support a model in which septin assembly is highly tunable by ionic conditions and membrane characteristics, allowing cells to regulate filament formation through localized changes in salt concentrations and lipid composition. Additionally, we explored septin localization and function in three black yeasts, Aureobasidium pullulans, Hortaea werneckii, and Knufia petricola, expanding our understanding of septin contributions to fungal morphology and polarization. Comparative sequence analyses suggest that black yeast septins possess subtle modifications at key polymerization interfaces, potentially affecting filament stability and membrane association. This study provides a framework for future investigations into septin biophysics and regulation in diverse fungal species, particularly in emerging model systems with newly developed genetic and recombinant tools.Doctor of Philosoph
Discovery of β-hydroxybutyrate binding proteins and their engineering as enhanced biological recognition elements for continuous biosensing
Get PDFβ-hydroxybutyrate (BHB) is a key physiological metabolite and biomarker, serving as a primary energy source for various cells and tissues during low glucose availability. There is significant academic and clinical interest in continuous BHB biosensing, with applications in the study and management of metabolic disorders. However, continuous monitoring of BHB remains challenging due to a lack of suitable biological recognition elements. Through this work, we discovered insights at the intersection of bacterial metabolism and biosensing technology through the identification of BHB binding proteins (BHBBPs), a new group of periplasmic solute-binding proteins (SBPs) that specifically interact with BHB. After recombinant production of BHBBPs, the specificity and affinity of each protein were thoroughly evaluated through an extensive analytical pipeline, including differential scanning fluorimetry (thermal shift assay) and tryptophan fluorescence spectroscopy (TFS). Binding data obtained from TFS revealed wild-type dissociation constants in the nano- to low micromolar range and suggested D-BHB, the natural enantiomer of BHB and human metabolite, as the preferred ligand for most tested proteins, including the proteins “Tt.2” from Thermus thermophilus, “EDC24” from Paucimonas lemoignei, and “NovoS” from Noviherbaspirillum sedimenti. These findings were corroborated further via isothermal calorimetry. Overall, 7 unique wild-type proteins were identified and biochemically characterized. Consequently, there is strong evidence for the classification of over 4000 putative proteins without previously-annotated function as hydroxyalkanoate binding proteins. These SBPs may facilitate cellular translocation of BHB through the membrane of certain prokaryotic organisms. Given the physiological range of BHB spans the micro- to millimolar range, it was necessary to adjust the binding constants of wild-type BHBBPs to improve their suitability for BHB biosensing. Structural analyses facilitated by machine learning based structural prediction, AlphaFold2, along with molecular docking and dynamics simulations, were used to identify key residues in the binding pocket and model the conformational dynamics of substrate binding/unbinding. Targeted point mutations in conserved polar residues of several BHBBPs reduced the binding affinity of the wild-type BHBBPs EDC24 and NovoS by more than 50-fold. Thus, BHBBPs were engineered through site-directed mutagenesis to achieve a collective affinity range covering nearly 4 orders of magnitude, from nanomolar to millimolar recognition of BHB. Leveraging the versatility of SBP-based biosensing, these receptors and their broad affinity range could facilitate the development of effective bioanalytical tools for BHB detection across diverse physiological environments.Doctor of Philosoph
Colored Torus Link Homology
Get PDFThe package of Type A link homology theories is controlled by (Type A) singular Soergel bimodules. Weintroduce several families of “Fray” functors on singular Soergel bimodules, modeled on constructions incategorical representation theory. We prove that each of these families gives rise to a corresponding familyof column-colored link homologies interpolating between existing constructions of column-colored homology.Finally, we use Fray functors to compute the column-colored HOMFLY homology of positive torus knots,resulting in the first verification of mirror symmetry conjectures for colored HOMFLY homology in nontrivialcolors.Doctor of Philosoph
Hiding Object Sizes with Constrained Padding in Multiple Settings
Get PDFAmong the most challenging traffic-analysis attacks to confound are those leveraging the sizes of objects downloaded over the network, as the size of an object is often a powerful indicator of its identity. In this dissertation, we consider this challenge in both (i) the simplified setting where successive object retrievals are assumed to be independent and (ii) the setting where sequential object retrievals are dependent on one another. Furthermore, within the dependent retrievals setting, we address the scenario where enumerating all possible sequences is impractical. For each setting, we present algorithms by which a benevolent object store computes a memoryless padding scheme to pad objects before sending them, in a way that bounds the information gain that the padded sizes provide to the network observer about the objects being retrieved. Furthermore, all of our algorithms ensure that no object is padded to more than c× its original size, for a tunable factor c > 1. We compare each algorithm to recent contenders in the research literature and evaluate their performance on practical datasets.Doctor of Philosoph
ALTERING THE PRE-RECOMBINATION EXPANSION HISTORY WITH HIDDEN SECTOR PHYSICS
Get PDFAlthough the standard model of cosmology, ΛCDM, accurately predicts a wide range of cosmological observables, discrepancies between early- and late-universe probes of the present-day expansion rate (H0) and small-scale clustering of matter point to the possibility that the ΛCDM model is incomplete. The maximum distance that sound waves traveled in the early universe, known as the sound horizon, subtends a precisely measured angle on the surface of the cosmic microwave background (CMB) that is used to infer a value of H0. Altering the pre-recombination expansion can reduce the size of the sound horizon and raise the CMB-inferred value of H0, reconciling CMB observations with direct measurements of the expansion rate from local probes. This dissertation investigates the observational signatures of several extensions to ΛCDM that introduce additional energy components to the early universe via a hidden sector - a theoretical set of particles that interact only weakly with the Standard Model. We first consider a hidden-sector particle that injects radiation into the early universe through its decay. We determine that current cosmological observations significantly constrain nonrelativistic particles that decay after Big Bang nucleosynthesis: the density of the decaying particles cannot exceed 3% of the total energy density of the universe. Next, we investigate the observational signatures of an axion-like scalar field that temporarily dominates the universe’s energy density well before matter-radiation equality. Such a period of scalar domination can enhance the growth of structure on sub-galactic scales without significantly altering the CMB. It has been proposed that present-day dark energy is sourced by a scalar field and that the H0 tension can be solved by the presence of a subdominant scalar field that becomes dynamical near matter-radiation equality. The detection of these unique signatures on sub-galactic scales would provide additional evidence for a collection of cosmological scalar fields, which is predicted by string theory.Doctor of Philosoph
“FROM THE FIELD TO THE FRONTLINE” BRIDGING THE GAP BETWEEN STIGMA AND MASCULINITY IN MENTAL HEALTH AMONG COLLEGE FOOTBALL PLAYERS AND MARINES
Get PDFThis study examines mental health stigma, masculinity, and help-seeking intentions in UnitedStates Marines and Division I football players. Utilizing a concurrent mixed-methods approach, the research combines quantitative measures, including the Self-Stigma of Seeking Help Scale (SSOSH), Stigma Scale for Receiving Psychological Help (SSRPH), Conformity to Masculine Norms Inventory (CMNI-22), Attitudes Toward Seeking Professional Psychological Help Scale (ATSPPH-SF), and the Mental Help-Seeking Intention Scale (MHSIS). Findings reveal similar levels of stigma, masculinity, and help-seeking intentions in both populations, highlighting a complex relationship between these factors. This pilot study underscores the need for further exploration into mental health within these environments, with implications for reducing stigma, challenging masculine ideals, and encouraging help-seeking behaviors. Despite limitations, the study contributes valuable insights into the mental health experiences of Marines and football players.Master of Art
Hippocampal-dependent neuroimmune mechanisms are associated with the effect of ethanol on stress-enhanced fear learning
Get PDFThe neurobiological mechanisms underlying comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are not well understood. We have previously demonstrated that chronic ethanol consumption and withdrawal exacerbates future stress-enhanced fear learning, a rodent model of PTSD-like behavior, supporting the idea that prior ethanol dependence induces vulnerability to future stressors. We have also shown that dorsal hippocampal astrocytes play a functional role in the development of this behavior, implicating the neuroimmune system in this phenotype. Thus, the current dissertation first sought to investigate the impact of chronic ethanol consumption and withdrawal on interleukin-1β (IL-1β), a proinflammatory cytokine, and glial fibrillary acidic protein (GFAP), a marker for astrocytes in the dorsal hippocampus (DH). We found that IL-1β expression in the dentate gyrus (DG) of the DH was increased following severe stress, while chronic ethanol consumption and withdrawal increased the expression of GFAP. Importantly, astrocytes were found to be the primary cell-type source of IL-1β, and chronic ethanol consumption and withdrawal increased the colocalization of IL-1β with GFAP. Given this association between IL-1β and astrocytes, we tested the specific functional role of dorsal hippocampal astrocyte-derived IL-1β in ethanol-induced alterations in future PTSD-like behavior. We employed a novel CRISPR/Cas9 technique to knockdown Il1b gene expression in dorsal hippocampal astrocytes. After validating this new technique, we found that knockdown of Il1b in dorsal hippocampal astrocytes had a modest effect in reducing ethanol’s augmentation of stress-enhanced fear learning. Collectively, these data support a partial role of dorsal hippocampal IL-1β in mediating ethanol- and stress-enhanced fear learning. These data ultimately support the involvement of hippocampal neuroimmune mechanisms in the development of comorbid PTSD and AUD.Doctor of Philosoph