Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Discipline
Institution
Keyword
Publication Year
Publication
Publication Type
File Type

Articles 45241 - 45270 of 818782

Full-Text Articles in Entire DC Network

A Second Wave Of Notch Signaling Diversifies The Intestinal Secretory Lineage, Eleanor Zagoren Jan 2025

A Second Wave Of Notch Signaling Diversifies The Intestinal Secretory Lineage, Eleanor Zagoren

Yale Graduate School of Arts and Sciences Dissertations

The small intestine is well known for its nutrient-absorbing enterocytes; yet equally crucial for homeostasis is a diverse set of secretory cells, all presumed to originate from the same intestinal stem cell. Despite their major roles in intestinal function and health, understanding how the full spectrum of secretory cell types arises remains a longstanding challenge, largely due to their comparative rarity. Here, I investigate the specification of a rare population of small intestinal epithelial cells found in rats and humans but not mice: CFTR high expressers (CHEs). Using pseudotime trajectory analysis of single-cell RNA-sequencing data from rat jejunum, I provide …

Go to article

Bridging Behavior And Neural Activity: Neural Dynamics Leading To Self-Initiated And Task-Driven Movements, Yongxu Zhang Jan 2025

Bridging Behavior And Neural Activity: Neural Dynamics Leading To Self-Initiated And Task-Driven Movements, Yongxu Zhang

Yale Graduate School of Arts and Sciences Dissertations

Understanding how populations of neurons generate behavior remains a fundamental question in neuroscience. While single-neuron analyses have provided valuable insights, behavior emerges from the coordinated dynamics of large neural ensembles that evolve over time and across states. A major difficulty is that neural population activity is non-stationary: it exhibits temporal distributional shifts, transitions between distinct dynamical regimes, and modulation by external or inter-regional inputs. Advances in artificial intelligence offer new opportunities to address this challenge. Yet, conventional models, such as standard recurrent neural networks, often fail to capture such complexity, limiting both predictive performance and mechanistic interpretability. This motivates the …

Go to article

The Organization Of Autophagic Membranes And Proteins At The Phagophore Assembly Site, Devin Michael Fuller Jan 2025

The Organization Of Autophagic Membranes And Proteins At The Phagophore Assembly Site, Devin Michael Fuller

Yale Graduate School of Arts and Sciences Dissertations

Autophagosomes are transient organelles which grow from a seed vesicle to encapsulate a target cargo and subsequently fuse with the lysosome to degrade its contents. This process occurs rapidly and requires the concerted effort of a host of unique membranes and proteins in a complicated cascade, which I detail in chapter I. Deletion of the lipid transport proteins ATG2A and ATG2B results in the accumulation of most of the preceding autophagic membranes and proteins in a large compartment. The ATG2 DKO compartment is advantageous as a model for the phagophore assembly site (PAS) for the following reasons: it is not …

Go to article

Visible-Light Mediated, Diastereoselective Epimerization Of Endocyclic, Exocyclic And Acyclic Amines, Maria Antonieta Vargas-Rivera Jan 2025

Visible-Light Mediated, Diastereoselective Epimerization Of Endocyclic, Exocyclic And Acyclic Amines, Maria Antonieta Vargas-Rivera

Yale Graduate School of Arts and Sciences Dissertations

Light-mediated stereochemical editing has become increasingly explored as a method for the stereoselective synthesis of compounds. This dissertation describes the work towards the stereoselective epimerization of amines. The first chapter describes the highly diastereoselective epimerization of endocyclic amines, which are commonly found in pharmaceuticals. The second chapter demonstrates the expansion of this light-mediated epimerization method to include exocyclic amines. Finally, chapter three details current advances towards the diastereoselective epimerization of acyclic amines.

Go to article

Incorporating Environmental Information Into Genetic Studies Of Psychiatric Disorders, Yue Hu Jan 2025

Incorporating Environmental Information Into Genetic Studies Of Psychiatric Disorders, Yue Hu

Yale Graduate School of Arts and Sciences Dissertations

Psychiatric disorders are among the most common diseases of humans, affecting a large number of individuals worldwide and contributing to a considerable burden of disease and disability. With a lifetime prevalence ranging from 5% to 17%, depression – characterized by a persistent low mood or loss of interest in activities for extended periods – is prominent amongst psychiatric disorders. Despite the availability of new medications developed over the past decade to treat depression, long-term treatment response remains disappointing; the risk of death by suicide is over 8-times national averages. Depression is multifactorial with both genetic and environmental factors, including demographic …

Go to article

Warm Life, Cold Stones: The Effigial Tomb In Late Medieval English Literature, Maia Ruth Béar Jan 2025

Warm Life, Cold Stones: The Effigial Tomb In Late Medieval English Literature, Maia Ruth Béar

Yale Graduate School of Arts and Sciences Dissertations

The effigial tomb is one of the defining features of Gothic sacred art. Tombs topped with grand effigies populated the churches, cathedrals, and chapels of late medieval England and many survive to this day. This dissertation explores the encounter with these tombs as represented in the literature of the period, in particular hagiography, romance, and narrative poetry. Although it literally demarcates the boundary between dead and living, the tomb is a powerful site of boundary-breaking in these texts at which the distinctions between life and death, flesh, and natural and artistic bodies are tested and often complicated. I consider various …

Go to article

Advancing Neuroimaging Brain-Behavior Machine Learning Biomarkers, Brendan Adkinson Jan 2025

Advancing Neuroimaging Brain-Behavior Machine Learning Biomarkers, Brendan Adkinson

Yale Graduate School of Arts and Sciences Dissertations

Machine learning models trained on human neuroimaging data are increasingly used as tools for predicting individual behavioral phenotypes and enhancing precision medicine. However, multiple limitations hinder their current scientific and future clinical utility. In this dissertation, I address key challenges surrounding "brain-behavior" predictive model interpretability, generalization, and bias. In Chapters 2 and 3, I show that prevalent feature selection practices overlook features that are meaningful for both prediction and neurobiological interpretation. This suggests that prevailing approaches lead to feature overinterpretation and a misrepresentation of the neurobiological bases of brain-behavior associations. In Chapters 4 and 5, I demonstrate that brain-behavior predictions …

Go to article

Distrust Of Psychotherapy For Biologically Explained Mental Disorders: A Validation Of Beliefs Underlying This Distrust And Interventions To Mitigate This Distrust, Annalise Perricone Jan 2025

Distrust Of Psychotherapy For Biologically Explained Mental Disorders: A Validation Of Beliefs Underlying This Distrust And Interventions To Mitigate This Distrust, Annalise Perricone

Yale Graduate School of Arts and Sciences Dissertations

Lay and scientific communities alike increasingly attribute mental disorders to biological causes (e.g., genetic risk or neurobiological abnormalities). Biological explanations of mental disorders have some beneficial consequences, including reduced personal blame of individuals affected by such disorders. One adverse consequence, however, is that upon learning that a mental disorder has a biological etiology, people tend to show reduced trust in the effectiveness of psychotherapy. Given that the combination of psychotherapy and pharmacotherapy is often optimal for many mental disorders, reduced trust of psychotherapy could result in poorer clinical outcomes, if people elect not to receive such treatment. Although this distrust …

Go to article

Psychedelic Action On Dendritic Structure And Function, Neil K. Savalia Jan 2025

Psychedelic Action On Dendritic Structure And Function, Neil K. Savalia

Yale Graduate School of Arts and Sciences Dissertations

Psychedelics are amid a scientific renaissance driven by their therapeutic promise for mental illnesses. This dissertation examines the neural mechanisms that underlie the acute and long- term actions of psilocybin, a serotonergic psychedelic found in magic mushrooms and an emerging rapid antidepressant. Here we used cutting-edge in vivo techniques to investigate psilocybin's effects in the medial frontal cortex of mice, with a focus on the structure and function of dendrites. Four key findings emerged. First, a single treatment with psilocybin induces persistent dendritic spinogenesis (Chapter 1). The drug-evoked changes in neuronal structure and function varies for subtypes of excitatory pyramidal …

Go to article

Kinetic And Thermodynamic Analysis Of Enpp1, Marisa Mary Michalchik Jan 2025

Kinetic And Thermodynamic Analysis Of Enpp1, Marisa Mary Michalchik

Yale Graduate School of Arts and Sciences Dissertations

The Ectonucleotide Pyrophosphatase Phosphodiesterase (ENPP) family members are promiscuous extracellular enzymes that play central roles in human physiology via catalysis of nucleotide and lipid substrates, but remain poorly characterized at the biochemical level. The founding member, ENPP1, is a glycosylated transmembrane enzyme with an extracellular catalytic domain that degrades nucleotide substrates (ATP and cGAMP) into their respective nucleotide monophosphates, playing a key role in both the regulation of biomineralization and innate immune system activation. The ENPP1 ATPase is the major source of extracellular pyrophosphate (PPi), the main chemical inhibitor of calcium phosphate crystal formation in physiology. ENPP1 deficiency lowers systemic …

Go to article

Investigating The Sequence Requirements For Translation Initiation By Viral Internal Ribosome Entry Sites, Sabrina Gulli Grunseich Jan 2025

Investigating The Sequence Requirements For Translation Initiation By Viral Internal Ribosome Entry Sites, Sabrina Gulli Grunseich

Yale Graduate School of Arts and Sciences Dissertations

Protein synthesis is both essential and highly regulated. This process is complex and requires the concerted effort of many protein factors. Some viruses have evolved ways to co-opt host translation during initiation by using internal ribosome entry sites (IRESs). These structured RNAs allow the virus to bind to the host's ribosome in the absence of canonical requirements. This dissertation focuses on relating the sequence of viral IRES elements to their role in initiating translation. The Cricket Paralysis Virus (CrPV) IRES is short, uses a simple mechanism, and can function in diverse cell-free systems making it a useful tool to study …

Go to article

Investigation Of How Long Noncoding Rna Pvt1 Regulates Myc Expression, Qiao Li Jan 2025

Investigation Of How Long Noncoding Rna Pvt1 Regulates Myc Expression, Qiao Li

Yale Graduate School of Arts and Sciences Dissertations

Long noncoding RNAs (lncRNAs) play essential roles in both physiological processes and disease, including cancer. A growing body of evidence positions lncRNAs as key regulators and biomarkers in tumorigenesis. Mechanistically, functional lncRNAs can regulate gene expression through epigenetic and transcriptional pathways, acting either via scaffold-like motifs that recruit regulatory complexes or through their abundance, which contributes to RNA-mediated feedback that modulates transcriptional condensates. Within the Plasmacytoma variant translocation 1 (Pvt1) locus, two alternative transcription start site isoforms have been identified: the constitutively expressed Pvt1a and the stress-inducible Pvt1b. While the precise functions of Pvt1a were not well understood, previous studies …

Go to article

Two Paradigms Of Research And Their Influence On The Study Of Animal Behaviour, David Fraser Jan 2025

Two Paradigms Of Research And Their Influence On The Study Of Animal Behaviour, David Fraser

General - Animal Cognition and Behavior

Taxonomist Roy Crowson identified a fundamental difference among sciences. What he called “natural history” is exemplified by classical biology; it begins by observing, describing and classifying phenomena in the real world, then seeks patterns and concepts that help to synthesize and explain the observations, and proceeds to measurement and experimentation grounded in that framework. What he called “natural philosophy” is exemplified by classical physics; it postulates fundamental principles or concepts that are thought to apply universally, and the research proceeds more directly to measurement and experimentation directed at these principles or concepts. The study of animal behaviour has been influenced …

Go to article

Perception Of Middle School Counselors About How To Increase The Enrollment Of Minority Students, Specifically African American And Hispanic, In The Health Science Curriculum At Empire High School, Charles S. Robertson Jan 2025

Perception Of Middle School Counselors About How To Increase The Enrollment Of Minority Students, Specifically African American And Hispanic, In The Health Science Curriculum At Empire High School, Charles S. Robertson

Doctor of Education Dissertations

This study explored the perceptions of middle school counselors regarding strategies to increase enrollment of minority students, specifically African American and Hispanic, in the health science curriculum at Empire High School. Utilizing a mixed methods convergent parallel design, this research integrated both quantitative and qualitative data to provide a comprehensive understanding of counselor viewpoints, existing barriers, and potential solutions. Lewin’s Change Model, as outlined by Burnes (2019), provided the theoretical framework for the analysis, guiding it through the stages of unfreezing existing mindsets, implementing change, and refreezing new practices. Quantitative data were collected via surveys administered to middle school counselors …

Go to article

A Phenomenological Exploration Of Students' Perceptions Of Social-Emotional Factors In Teacher-Student Relationships And Its Impact On Academic Achievement Of Impoverished High School Youth, Jeannine L. Carrington Jan 2025

A Phenomenological Exploration Of Students' Perceptions Of Social-Emotional Factors In Teacher-Student Relationships And Its Impact On Academic Achievement Of Impoverished High School Youth, Jeannine L. Carrington

Doctor of Education Dissertations

This phenomenological study explored the experiences of former students from a Title I high school in a disadvantaged urban community, focusing on how socio-emotional factors in teacher-student relationships influenced academic achievement. Grounded in Bandura’s (1977) social learning theory and the CASEL (2017) social-emotional learning (SEL) framework, the study examined how teacher encouragement, emotional support, and expectations impacted student motivation and persistence. Twenty alumni participated in semi-structured interviews, analyzed using Braun and Clarke’s (2006) thematic analysis. Five themes emerged: teacher encouragement, emotional support, high expectations, cultural awareness, and long-term impact. Findings suggest that emotionally supportive, trusting relationships foster self-efficacy, engagement, and …

Go to article

Teacher Perceptions Of Social-Emotional Learning In A Covid-Impacted Environment, Gina Gold Jan 2025

Teacher Perceptions Of Social-Emotional Learning In A Covid-Impacted Environment, Gina Gold

Doctor of Education Dissertations

Social-emotional learning (SEL) builds students’ resilience skills, which impact the biology of the brain connected to emotional regulation, safe behaviors, and positive learning outcomes. Diminished resilience is typically the result of childhood trauma, which affects physical and emotional health into adulthood. Teachers’ capacity, implementation, and data analysis practices for SEL are important to support building resilience skills in our students to help them grow to be emotionally and physically healthy citizens. The purpose of this research study was to investigate the perspectives of elementary school teachers from four elementary schools in the same school district in rural, southwestern North Carolina …

Go to article

Investigating Teacher Self-Efficacy And Teacher Attitudes Toward Stem In North Carolina High School Science And Mathematics Classrooms, Kelly J. Ruff Jan 2025

Investigating Teacher Self-Efficacy And Teacher Attitudes Toward Stem In North Carolina High School Science And Mathematics Classrooms, Kelly J. Ruff

Doctor of Education Dissertations

The purpose of this investigation was to determine if North Carolina high school science and mathematics teachers differ in their STEM teacher self-efficacy, outcome expectancy, and attitudes toward STEM instructional practices. The data collection instrument used in this study was the T-STEM survey. Science and math teachers voluntarily participated in the study and answered Likert-type survey items focusing on STEM teacher self-efficacy, STEM instructional practices, and outcome expectancy. Additionally, study participants answered demographic questions on gender, years of teaching experience, and the type of degree earned. Sub-scores for each survey section were calculated and analyzed with descriptive and inferential statistical …

Go to article

Teacher And Parent Perspectives Of Young Children's Development Since The Covid-19 Pandemic In A Rural Public School District, Regina L. Lineback Jan 2025

Teacher And Parent Perspectives Of Young Children's Development Since The Covid-19 Pandemic In A Rural Public School District, Regina L. Lineback

Doctor of Education Dissertations

Face to face education for young children was interrupted in March of 2020 due to mandatory school closures precipitated by the COVID-19 pandemic. Virtual learning was forced upon teachers and students at a time when many families and teachers had limited or no access to internet. When face to face learning resumed, teachers and students were required to wear facial masks and maintain social distancing protocols. This study sought to explore teacher and parent perspectives of young children’s development in a rural public school district since the COVID-19 pandemic. A qualitative study was completed using teacher interviews, a teacher focus …

Go to article

Description’S Displacements: Writing Experience In Musil, Benjamin, And Bachmann, Aida Feng Jan 2025

Description’S Displacements: Writing Experience In Musil, Benjamin, And Bachmann, Aida Feng

Yale Graduate School of Arts and Sciences Dissertations

This dissertation unfolds the ways in which description emerged as an active site for reconfiguring human experience in the writing experiments of the 20th century. Description, as a procedure for presenting and arranging the phenomena of reality, typically constructs an epistemological realm of experience that progresses toward comprehension and internal consistency. Understood in this way, description mediates one kind of experiential reality while foreclosing others. This project enlarges description’s operative capabilities toward a presentational mode that does not merely re-describe the phenomenal objects in this reality. To do so, it foregrounds writers and thinkers who conversed directly with philosophical traditions …

Go to article

Functional Roles Of Subcellularly Localized Glycolytic Isoforms Of Glucose 6-Phosphate Isomerase, Ian Joseph Gonzalez Jan 2025

Functional Roles Of Subcellularly Localized Glycolytic Isoforms Of Glucose 6-Phosphate Isomerase, Ian Joseph Gonzalez

Yale Graduate School of Arts and Sciences Dissertations

While metabolic pathways are largely conserved across cells and organisms, tissues exhibit metabolic heterogeneity that tailors metabolism to their physiological demands. How the conserved pathways of metabolism achieve metabolic heterogeneity is incompletely understood, particularly in vivo. In this dissertation, I investigate the genetic requirement of glucose 6-phosphate isomerase (GPI-1), a conserved glycolytic enzyme that also regulates the pentose phosphate pathway (PPP). Using CRISPR-Cas9 genome editing, I found that gpi-1 knockout animals display germline defects consistent with impaired PPP, and somatic defects consistent with impaired glycolysis. I discovered that GPI-1 isoforms are differentially expressed and localized: GPI-1A is cytosolic in all …

Go to article

Epidemiologic And Immunologic Characterization Of The Post-Acute Sequelae Of Covid-19, Christine Marie Miller Jan 2025

Epidemiologic And Immunologic Characterization Of The Post-Acute Sequelae Of Covid-19, Christine Marie Miller

Yale Graduate School of Arts and Sciences Dissertations

Since its emergence in late 2019, SARS-CoV-2 has infected over 15 million people—and the number continues to rise. The global impact of this novel coronavirus has been profound, reshaping not only public health infrastructure but also our understanding of human biology. The full extent of the virus’s effects on the immune system remains incompletely understood and will likely take years to fully unravel. What is already evident, however, is that SARS-CoV-2 uniquely modulates both innate and adaptive immunity, with consequences that span the developmental spectrum—from fetal and pediatric stages through adulthood. While many individuals recover without overt clinical sequelae, an …

Go to article

Glycolysis-Induced Acidification Links Mitochondrial Deficiency To Axon Degeneration, Hadas Dabas Jan 2025

Glycolysis-Induced Acidification Links Mitochondrial Deficiency To Axon Degeneration, Hadas Dabas

Yale Graduate School of Arts and Sciences Dissertations

Axons extend far from the neuronal soma and depend on local energy metabolism to sustain signaling and structural integrity. Mitochondria are normally abundant in axons, where they provide numerous utilities. In many neurodegenerative diseases, however, mitochondrial function or trafficking is impaired, but the mechanisms linking mitochondrial loss to axon degeneration remain unclear.In this dissertation, I use C. elegans mitochondrial trafficking mutants, in which axons completely lack mitochondria, to define the metabolic basis of degeneration. I find that glycolysis, typically viewed as a protective energy source, unexpectedly promotes axon breakdown. Elevated glycolytic flux in axons without mitochondria leads to accumulation of …

Go to article

Molecular Investigation Of Signaling Molecules Involved In Cerebrovascular Disorders, Kimberly Jean Vish Jan 2025

Molecular Investigation Of Signaling Molecules Involved In Cerebrovascular Disorders, Kimberly Jean Vish

Yale Graduate School of Arts and Sciences Dissertations

The most common forms of cerebrovascular malformations are brain arteriovenous malformations (AVM), often caused by genetic mutations in the EphB4-p120RasGAP signaling pathway, and cerebral cavernous malformations (CCM), often caused by genetic mutations in the CCM signaling pathway. These pathways are well studied, but there are clear deficiencies in the molecular level understanding of how signals are transduced. Relevant to AVM, the GTPase activating protein (GAP) for Ras, p120RasGAP, is necessary for downregulating Ras signaling during vascular development, and loss of its activity is associated with impaired cerebrovascular development. In my thesis, I investigate how p120RasGAP uses its Src-homology 2 (SH2) …

Go to article

Studies On The Structural Basis Of Oxygenic Photosynthesis, David Flesher Jan 2025

Studies On The Structural Basis Of Oxygenic Photosynthesis, David Flesher

Yale Graduate School of Arts and Sciences Dissertations

Oxygenic photosynthesis — performed on all seven continents by green plants, algae, and cyanobacteria — supports the global biome through its ability to capture and store light energy. This is achieved through a series of protein complexes collectively known as the photosynthetic apparatus. During my PhD research, I’ve investigated the structural basis for how these protein complexes capture this light energy and transduce it to redox energy. My thesis work, summarized in this dissertation, can be grouped in two broad research themes: (i) structural studies on Nature’s water oxidation reaction, explored in Part I of this dissertation; and (ii) the …

Go to article

Cell State Dependent Strategies For Resolving Fundamental Properties Of Ligands Via Receptor Processes, Andrew Goetz Jan 2025

Cell State Dependent Strategies For Resolving Fundamental Properties Of Ligands Via Receptor Processes, Andrew Goetz

Yale Graduate School of Arts and Sciences Dissertations

Ligands may carry information through features such as their concentration, identity, and spatial distribution. Cells that can resolve these properties gain access to additional dimensions of information which may be beneficial as certain ligand properties possess unique features (e.g., ligand identity does not disperse with distance the way concentration does). Cells can accomplish this, at least in part, through the use of signaling cascades initiated by membrane receptors which bind to the ligand and activate downstream processes. The properties of these signaling cascades depend on the "state" of the cell (a property encompassing important cell features like protein levels and …

Go to article

Coordinated Wnt And Shh Signaling In Hair Follicle Mesenchyme Development And Regeneration, Yiqun Jiang Jan 2025

Coordinated Wnt And Shh Signaling In Hair Follicle Mesenchyme Development And Regeneration, Yiqun Jiang

Yale Graduate School of Arts and Sciences Dissertations

Developmental morphogenesis requires cells to balance proliferation with differentiation, often regulated by multiple signaling pathways. While most studies consider these pathways as additive, less is known about how they interact to regulate fate transitions. In this dissertation, I use the hair follicle dermal condensate (DC), the first differentiated mesenchymal population of the skin with the ability to instruct new hair growth, to study morphogens interact to regulate the dermal mesenchyme.Wnt and SHH are necessary and sufficient for DC formation, during which cell cycle exit with molecular DC gene expression occur simultaneously. Interestingly, high Wnt alone is sufficient to induce cell …

Go to article

Smart Synthesis: Harnessing Electrochemistry To Enhance Catalytic Water Treatment, Aidan Francis Meese Jan 2025

Smart Synthesis: Harnessing Electrochemistry To Enhance Catalytic Water Treatment, Aidan Francis Meese

Yale Graduate School of Arts and Sciences Dissertations

Catalytic water treatment technologies hold great promise for degrading even the most recalcitrant contaminants of emerging concern (CECs). Heterogeneous catalytic processes are especially appealing, providing the benefits of easy catalyst recovery and reduced risk of secondary pollution. However, heterogeneous reactions often suffer from mass transfer limitations, and the development of catalyst materials that are sufficiently active, selective, and stable under the conditions necessary for pollutant degradation remains challenging. Furthermore, synthesis of catalyst materials, particularly those with desirable catalytic properties and novel architectures, are often time- and energy-intensive and involve expensive materials and/or equipment. In this work, we address these challenges …

Go to article

Nanoporous Inp And Its Application In Short-Wave Infrared Vertical-Cavity Surface Emitting Lasers, Chenziyi Mi Jan 2025

Nanoporous Inp And Its Application In Short-Wave Infrared Vertical-Cavity Surface Emitting Lasers, Chenziyi Mi

Yale Graduate School of Arts and Sciences Dissertations

The Short-Wave Infrared (SWIR) range is a crucial wavelength window with a wide range of applications. Just to name a few, it covers the important telecommunication bands, provides advantages in bio-sensing and there are emerging applications recently such as noninvasive glucose monitoring, eye-safe 3D sensing and Si photonics. The development of SWIR vertical cavity surface emitting lasers (VCSELs) has been ongoing for more than 30 years but has not yet led to commercialization. The main reason is that it hasn't been easy to build highly reflective distributed Bragg reflectors (DBRs). Unlike the GaAs systems, materials lattice-matched to InP suffers from …

Go to article

Streamlining Drug Discovery With The Aid Of Artificial Intelligence And Physics-Based Modeling, Anastasia Saar Jan 2025

Streamlining Drug Discovery With The Aid Of Artificial Intelligence And Physics-Based Modeling, Anastasia Saar

Yale Graduate School of Arts and Sciences Dissertations

The drug discovery pipeline is both expensive and prone to high attrition rates with many compounds failing in late-stage clinical trials. Computer-aided drug design (CADD) has emerged as a pivotal part of the pipeline to mitigate these challenges by enabling earlier and more cost-effective assessment of compound viability. This work focuses on two major aspects of CADD: absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions and free energy calculations. First, neural network models are developed for the prediction of aqueous solubility and cytotoxicity, two key contributors to late-stage drug attrition. Ensemble models of graph convolutional networks (GCNs) and graph attention …

Go to article

Development Of The Human Brain Networks During Infancy, Huili Sun Jan 2025

Development Of The Human Brain Networks During Infancy, Huili Sun

Yale Graduate School of Arts and Sciences Dissertations

In early infancy, the human brain undergoes rapid network construction and remodeling. Advances in neuroimaging have made non-invasive, in-vivo observation of these brain changes possible during the perinatal period. However, how the brain develops to support dynamic activity and cognitive function remains unclear. In this thesis, I leverage the network control theory to model brain controllability - the capacity to drive activity changes - and examine its role in neurodevelopment. I first outline the developmental trajectories of controllability during the perinatal period and link them to synaptogenesis with cross-species models. Next, I introduce a machine-learning framework to explore how white …

Go to article

First Prev Next Last