22689 research outputs found
Sort by
CYTOSKELETAL REGULATION OF EXCITABILITY IN CELL MIGRATION
No full textIn the social amoeba Dictyostelium, cells regulate their motility through two intercon-
nected excitable networks: the Signal Transduction Excitable Network (STEN) and the Cy-
toskeletal Excitable Network (CEN). The slower and more diffusive STEN organizes and
connects to the faster, less diffusive CEN, enabling the cells to coordinate their responses
to internal and external cues, guiding their directional movement.
In my PhD I have explored two aspects of how cells coordinate the actions of STEN
and CEN. In this thesis, I first explore the role of feedback loops within and between CEN
and STEN in establishing and maintaining cell polarization, which is sustained directional
movement through the development of stable symmetry breaking. Polarization is typi-
cally initiated by local positive feedback that reinforces the formation of a stable leading
edge. Many models posit that global inhibition mechanisms prevent the initiation of multi-
ple fronts, thereby stabilizing polarization. However, experimental evidence suggests that
inhibitory mechanisms might be localized to the back of the cell, rather than acting as
a global signal. While models incorporating localized rear inhibition showed promise in
capturing experimental results, they struggled to consistently maintain a stable polarized
state. To address this, we explored a novel mechanism involving the dynamic partitioning of back molecules. Supported by experimental data, this mechanism successfully captures
the establishment and persistence of the polarized state, providing a more comprehensive
understanding of Dictyostelium cell migration.
Next, I examine how cells move on surfaces with nano-ridges, aligning their movement
with the ridge orientation. Our findings suggest that nano-ridges enhance both the lifetime
and activity of CEN, which in turn confines and organizes STEN waves through negative
feedback. As the ridges become taller, cells are able to discern the curvature differences
between the concave and convex regions of the surface, resulting in distinct patterns of
activation and deactivation in STEN and CEN based on surface topography.
Cells can trigger the formation of protrusions when stimulus or biological stochasticity
pushes the system over a threshold. In a theoretical, I explore the biological advantage
of the cell being close to the threshold and how a system can adaptively tune itself to get
closer to excitability
Artificial Intelligence Data Centers and United States Based Hyperscalers: Impacts and Solutions
Get PDFArtificial intelligence (AI) is becoming a much bigger part of everyday life, and it is driving a significant rise in electricity demand across the world. A large part of this growing demand comes from powerful new data centers designed to support AI systems, which often require far more electricity than traditional data centers. Running AI models requires significant energy expenditure, especially during training, but it is the repeated use of those models, called inference, that creates the largest and most ongoing demand. The first part of this paper reviews recent research showing how AI is increasing global computing needs and what that means for energy systems and climate goals. Then it delves more broadly into hyperscalers, the large tech companies such as Amazon, Microsoft, Google, and Meta that are building many of the world’s biggest data centers. While not all of the facilities they are building are meant specifically for AI, they all require massive amounts of electricity and are expanding quickly. This is especially true in areas like Northern Virginia, where land is available, power is relatively cheap, and local governments are supportive. This clustering of hyperscale data centers places growing pressure on local electric grids and increases the need for more power generation, transmission infrastructure, and energy storage. Using Virginia as a case study, this paper looks at how hyperscaler growth is changing energy demand at the regional level, what kinds of strain this puts on utilities and clean energy planning, and what policies may be needed to keep the grid reliable while also meeting climate goals
Mental Health Problems, Substance Use, and Childhood Trauma in Chinese College Students
No full textSubstance use and mental health disorders among college students are pressing global public health issues, with Chinese students increasingly impacted. This study addresses the prevalence and associations of substance use (cigarettes, e-cigarettes, and alcohol) with mental health disorders, including depression, anxiety, and PTSD, among Chinese college students. It further examines the influence of childhood trauma and lifestyle factors, such as physical exercise and sleep quality, on these conditions.
A cross-sectional survey was conducted from October 26 to November 18, 2021, involving 96,151 students from 64 universities in Jilin Province, China. The survey collected data on demographic characteristics, substance use behaviors, mental health symptoms, childhood trauma experiences, and healthcare access. Statistical analyses, including logistic regression, were performed to identify relationships between substance use, mental health disorders, and related factors.
The results revealed a high prevalence of substance use, with alcohol being the most commonly reported substance (59.64%) and 13.24% of students using cigarettes. Mental health disorders were prevalent, with depression affecting 50.38%, anxiety 36.77%, and PTSD 19.71% of participants. Substance use was strongly associated with undiagnosed mental health issues, highlighting significant gaps in healthcare access. Childhood trauma, including emotional, physical, and sexual abuse, significantly increased vulnerability to substance use and mental health disorders. Lifestyle factors, such as poor sleep quality and lack of physical exercise, further exacerbated these challenges.
The findings emphasize the urgent need for integrated interventions addressing substance use and mental health among college students in China. Tailored prevention strategies, including improved mental health services, trauma-informed care, and lifestyle interventions, are critical. Policymakers, educators, and healthcare providers must collaborate to foster supportive environments and enhance students' overall well-being
NON-INVASIVE ASSESSMENT OF PANCREATIC DUCT HYPERTENSION USING COMPUTATIONAL MODELING
No full textChronic pancreatitis is frequently accompanied by pancreatic ductal hypertension, which drives patient morbidity and impairs exocrine function. We propose a fully non-invasive diagnostic framework that couples high resolution Magnetic Resonance Cholangiopancreatography (MRCP) with two complementary flow-analysis tools:
(i) patient-specific three-dimensional (3D) Computational Fluid Dynamics (CFD) simulations that resolve detailed intraductal pressure fields under physiologically realistic boundary conditions, and (ii) a quasi-one dimensional (quasi-1D) analytical model, derived from the axisymmetric Navier Stokes equations, that offers rapid pressure-drop predictions along the duct centerline.
MRCP data sets from chronic pancreatitis patients were reconstructed into 3-D duct geometries and meshed for CFD. The quasi-1D model, requiring only the local cross-sectional area and a calibrated momentum-correction factor α, delivered pressure estimates within 8% of the CFD results while reducing computation time by two orders of magnitude. Validation with 3-printed phantom ducts confirmed excellent agreement between experimentally measured and simulated pressures (R2 = 0.97), and clinical comparison against intra-ductal manometry during ERCP showed a similarly strong correlation (R2 = 0.93). Simulated pressure drops also aligned with postoperative pain-relief scores, underscoring translational relevance.
Limitations: current models assume Newtonian, steady-state flow in rigid walls and employ spatially uniform secretion; wall compliance, non Newtonian rheology, and time-varying secretion will be addressed in future work.
Overall, the MRCP–CFD–analytical procedure accurately predicts ductal hypertension and offers a fast, non invasive decision-support tool for managing chronic pancreatitis. The quasi-1D model, in particular, enables bedside screening without sacrificing diagnostic accuracy
DECENTRALIZED BIOBANKING (DCB) IN THE POST-COVID ERA: ADDRESSING THE LACK OF DIVERSITY IN BIOBANKING BY EXPANDING REACH, NAVIGATING CHALLENGES, AND FINDING THE HYBRID FUTURE
Get PDFThe COVID-19 pandemic exposed the critical need for diverse biobanks, exposing the limitations of traditional, centralized models. Decentralized biobanking (DCB), empowered by technological advancements and a growing emphasis on patient-centric approaches, offers a powerful solution to address this lack of diversity by expanding reach into underserved communities. However, realizing DCB's full potential requires navigating significant logistical, ethical, and
technological challenges. This thesis argues that a hybrid model, strategically integrating decentralized elements within existing centralized infrastructures, represents the most viable path towards a more equitable and inclusive biobanking future
Extrinsic and Intrinsic Factors that Affect Clinical Outcomes in SIV-Infected Macaques
Get PDFViral infections, such as human immunodeficiency virus (HIV), are a growing public health threat for which there continue to be limited curative and treatment options. In addition, the clinical consequences of infection vary widely between individuals, making treatment needs and outcomes difficult to predict. This project focuses on utilizing an established model, simian immunodeficiency virus (SIV) infection in macaques, to understand how immune responses differ between individuals, and how this in turn affects the clinical outcomes of infection. Both extrinsic and intrinsic factors that affect host immune responses to infection are characterized in detail, with a specific focus on the significance of psychosocial stress in SIV as well as the role of antiviral antibody responses in central nervous system outcomes. Chapter 2 discusses single housing of macaques as a model of chronic psychosocial stress; single housing blunted innate immune responses in monocytes and platelets during the initial 14 days post-infection when compared to socially housed macaques. Chapter 3 presents a separate cohort of macaques, wherein failure to seroconvert against SIV in plasma was predictive of development of SIV encephalitis, characterized by both localized viral replication and myeloid-driven inflammation. Although focused on specific contexts, both investigations demonstrate the dramatic variation in clinical outcomes that can be driven by factors independent from the pathogen itself. This project contributes to a more robust understanding of the predisposing and protective factors of outcomes of infection, and this knowledge can inform proactive approaches to mitigating the impact of viral diseases
AUTONOMOUS ROBOTIC SOLUTIONS FOR DIAGNOSTIC AND INTERVENTIONAL TRAUMA APPLICATIONS
No full textUnintentional trauma remains a leading cause of death in the United States, with up to 29% of pre-hospital trauma deaths deemed potentially preventable through timely hemorrhage control. Significant advancements have been made in trauma diagnostics and interventions, including the Focused Assessment with Sonography for Trauma (FAST) examination, which has become an effective point-of-care imaging method for rapidly detecting life-threatening injuries and intra-abdominal free fluid without the use of radiation. Similarly, the Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) offers a minimally invasive approach to controlling non-compressible abdominal hemorrhage via femoral artery access, helping maintain vital organ perfusion and improving patient survival chances. However, despite the proven efficacy of these and similar trauma care methods, they all face two critical challenges: they rely on the physical presence of skilled physicians, and are heavily dependent on operator expertise for optimal outcomes. Consequently, neither FAST nor other minimally invasive interventional stabilizing procedures have been incorporated into pre-hospital protocols, underscoring a critical gap in early trauma care delivery. This thesis seeks to address these limitations by introducing autonomous robotic solutions for both trauma diagnostics and intervention, aiming to provide consistent, high-quality care during the critical early phases of trauma treatment.
The key contributions of this dissertation include: (1) the creation of the first non-commercial patient-specific FAST examination phantom featuring perihepatic, perisplenic, and perivesical hemorrhages, offering a durable and realistic platform for validating robotic trauma diagnostic systems; (2) the development and public release of a new abdominal skin dataset that establishes a benchmark for validating skin segmentation algorithms in trauma applications, and improves existing skin segmentation techniques, enabling more reliable autonomous robotic scanning; (3) the development of an autonomous robotic system with a force-based US scanning protocol for thoracoabdominal imaging, validated through simulation and physical experiments that address previously unexplored anatomical complexities; (4) the development of an autonomous US-guided robotic system for femoral artery access, establishing the first end-to-end trauma-specific solution, with validation on 5 complex patient-specific phantoms demonstrating 100% first-attempt success in arterial access; and lastly, extending the work for vascular needle placement to improve on the targeting accuracy of flexible needles, (5) the development of a mechanics-based framework for flexible bevel-tip needle insertion, integrating a non-linear tissue-interaction model and robust controller that demonstrate superior needle deflection prediction in phantoms with more than 3 tissue layers, and improved targeting accuracy under parameter uncertainty in simulation. Collectively, these contributions pave the way towards autonomous robotic care in trauma.
This thesis presents the first autonomous robotic systems for US-guided diagnostics and minimally invasive interventions in trauma, validated using patient-specific phantoms that advance current experimental standards. The scientific contributions of this work establish a foundation for advancing robotic integration in emergency medicine, with applications extending beyond trauma care
Hispaniola’s Lost Rodents and Niches: Integrating 3D/2D Reconstructions with Data Visualization, Isotopes, and Anatomical Analysis
Get PDFDuring the Holocene, the island of Hispaniola supported the greatest rodent family diversity in the Caribbean and was even hypothesized to have been the center of regional evolutionary radiation. Today, only one endemic and historically endangered rodent survives—Plagiodontia aedium—alongside the invasive species Rattus rattus and Rattus norvegicus (Morgan & Woods, 1986; Woods & Sergile, 2001). Hispaniola’s highly endemic, specialized fauna make it a valuable model for understanding local and global extinction patterns as well as conservation strategies. Yet, the ecology of the singular extant Hispaniolan rodent P. aedium is severely underexplored, making it susceptible to extinction.
This project reconstructs the zygomasseteric system and dentition of extinct hystricomorphous rodent species Brotomys voratus, Isolobodon portoricensis, Hexolobodon phenax, and extant species Plagiodontia aedium and the invasive Rattus spp. The anatomical arrangement of the zygomatic arch and masseter muscles in rodents are particularly specialized in mastication (mechanics) between species. The major divisions of the masseter muscle (superficial, medial, and deep) give rise to clues regarding chewing processes and dietary niches. Supplemental data findings of carbon δ13C and oxygen δ18O isotopes in the tooth enamel of each respective rodent species were also analyzed in conjunction with the anatomical reconstructions. The combination of bony anatomy, muscular reconstructions, and isotopic data allows for a more complete analysis of each species’ ecological adaptations.
Variations in skull structures, bony landmarks, and masseteric arrangements among extinct species were identified. Three-dimensional skull reconstructions and evidence-based illustrations were generated with discussions correlating anatomy to isotopic enamel data of the select extinct rodent fossils. Making a comparative analysis with data visualization between extinct rodents, the extant P. aedium, and invasive Rattus spp. provides additional context.
We can better inform our conservation efforts by studying the foraging habits, dietary patterns, and ecological niches of these species. Investigating stable carbon and oxygen isotopes from tooth enamel and fossils will improve our understanding of these fascinating creatures and protect those still with us
Exploring Mechanical Memory in Acral Melanoma
Get PDFAcral melanoma (AM) arises in the volar skin such as soles and palms. It is more aggressive than cutaneous melanoma (CM), which mostly arises in non-volar skin such as the trunk and arms. The reason why AM is more aggressive remains unclear. Given that volar skin has higher extracellular matrix stiffness, this study investigated how increased stiffness contributes to the aggressive behavior of AM and induces mechanical memory. This allows AM to remember the stiff volar environment and continue activating mechanical signaling induced by the stiff environment even after metastasizing to softer organs. Using polyacrylamide hydrogels of varying stiffness, I found that stiffer environments activated mechanical signaling molecules including YAP and its downstream targets, such as CTGF, CYR61, and AXL. Increased stiffness also induced gene expression signatures related to invasion, limb development, and a volar-like transcriptional program. In vivo treatment with the YAP inhibitor K-975 reduced metastasis, suggesting a role for YAP in driving AM aggressiveness. Furthermore, I found that AM cells possess mechanical memory, maintaining YAP activation even after being transferred to softer substrates. Further studies are needed to uncover the mechanisms of mechanical memory and blocking the mechanical memory in AM might be a potential therapy
Freshwater fish and the K/Pg boundary: Integrative studies of morphology, evolution, and the origins of modern biodiversity
No full textThree evolutionary processes have shaped the phylogeny of all organisms: the vertical and horizontal components of evolutionary change and extinction. This third process, extinction, reaches perhaps its most influential in deep time events known as mass extinctions. Mass extinctions punctuate the history of life, overturning stable environments and allowing the growth and development of subsequent faunas and floras. Because of this tremendous revolutionary power, the modern fauna is, in many ways, the result of the filtering of the most recent mass extinction event, that which defines the Cretaceous/Paleogene (K/Pg) boundary. The recency of this event, the purported extraterrestrial cause, and the fate of perhaps its most famous victims, the non-avian dinosaurs, have resulted in extensive study of survivorship across the boundary. Vertebrate groups have received much of this attention. However, one notable gap in our understanding is the survival and extinction of freshwater actinopterygians, which today comprise ~25% of vertebrate diversity. In my dissertation work, I conducted three studies to provide different empirical perspectives on the diversity dynamics of freshwater fish and assess the challenges that underly further clarification of this portion of the history of Life. First, I described and analyzed the articulated fossil of a large gar (Lepisosteiformes) that lived only ~2000 years after the K/Pg event. Then, I used a case study of the fossil record of Esociformes to assess the challenges and opportunities that underly use of the fragmentary and isolated specimens that comprise the majority of the near-K/Pg freshwater fish fossil record. Finally, I used sources of evidence and methods available right now in an integrative assessment of survivorship of freshwater fish across the K/Pg. Together, my dissertation represents a multifaceted approach to the empirical and theoretical problem of freshwater fish K/Pg diversity dynamics and makes demonstrable contributions to our understanding of both that event and the attendant challenges of reconstructing the deep history of Life