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    194341 research outputs found

    Adaptive Data Driven Network Slicing and Resource Blocks Assignment Using Deep Reinforcement Learning

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    Network management complexity poses a significant challenge for dynamic prospicient grid environments. Methodologies integrating advanced machine learning techniques offer an opportunity to address these challenges. Among these, deep reinforcement learning (DRL) promises abilities to proactively monitor network resources while simultaneously analyzing device behavior, traffic patterns, and network capabilities. Coupled with the key abilities of DDDAS paradigm for creating an infosymbiotic feedback loop for data and measurement steering, these methodologies could break grounds for dynamic resource management. In this preliminary research work, we propose an adaptive data driven network slicing framework for prospicient grids using deep reinforcement learning. Once trained, the DRL dynamically adjusts network slice capacities and assignment using real-time data to foster continuous improvement, proactively anticipating future requirement changes to scheduling. Proposed DDDAS-based approach offers adaptability in resource management for evolving smart grid demands

    Examining Natural Seed Dispersal Interactions in the Caribbean Archipelagos and Their Status in the Anthropocene

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    Plant-animal mutualisms, particularly frugivory, influence ecosystems by playing key roles in plant and animal life histories. These interactions are threatened by disturbances like defaunation and the proliferation of invasive species. Given these risks, it is important to assess their status to define conservation priorities and the abilities of species to adapt when facing threats. Here, I researched plant-frugivore interactions in the Caribbean archipelagos, an understudied biological hotspot. My goal is to expand our understanding of frugivory, and how anthropogenic effects shape this important process. To do so, I 1) investigated spatial associations between frugivore and plant distributions, 2) evaluated the loss of frugivory function due to declining large animal populations and determined its effects on germination, 3) assessed how frugivory dynamics react to non-native mammals, and 4) explored an alternative, abiotic dispersal method that plants may use in the absence of frugivore partners. I used multiple methods including spatial analysis, germination trials, field assessments, and movement modeling in this pursuit. I found that plant-frugivore relationships are threatened in the region, with common frugivores having many times smaller ability to interact with fruits than threatened reptiles. Meanwhile higher non-native mammal activity was associated with significant declines in native frugivory interactions. Given that I found links between frugivorous animal and fruiting plant distributions, the erosion of plant-frugivore interactions bodes poorly for plants and the animals that depend on them. Fortunately, my results indicate that successful restoration and conservation of Caribbean megafauna populations could re-establish eroded interactions. Furthermore, I find evidence that some fruiting&nbsp;species benefit from dispersing across the region through ocean-currents.&nbsp;Overall, I demonstrate the importance of maintaining&nbsp;healthy mutualistic interactions and lay the foundation for future conservation and research efforts.</p

    The Epidemiology of the Long-term Care Needs of Older Adults in the United States: An Analysis of the HERO CARE Survey and National Health and Aging Trends Study

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    The 65 and over population will more than double by 2050 and become more racially and ethnically diverse. With the projected demographic shift, supporting older adults with long-term care (LTC) needs is a public health priority. LTC includes long-term services and supports (LTSS) designed to help with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). First, we aimed to evaluate the dynamic cross-sectional, autoregressive, and cross-lagged associations between the intensity of weekly care hours, total LTC needs and total unmet LTC needs among community-dwelling older adults aged 65 and over in the United States who participated in the National Health and Aging Trends Study. We applied a random intercept cross-lagged panel model and found reciprocal associations between intensity of weekly care hours and total number of LTC needs in later years. Second, we used data from the HERO CARE survey to 1) characterize Veterans across levels of hierarchy of ADL and IADL problems, 2) compare Veterans across degree of need for help, and 3) identify the prevalence of ADL and IADL combination patterns. Our findings demonstrate that Veterans are demographically and clinically different by the hierarchy of ADL and IADL impairment and degree of need for help. Third, we aimed to 1) describe the prevalence of being homebound by race, ethnicity and rurality among Veterans with ADL or IADL problems, 2) describe the characteristics of homebound and non-homebound Veterans, 3) evaluate the prevalence of ADL and IADL unmet needs overall and by homebound status, race, ethnicity, and rurality, and 4) evaluate the association between homebound status and ADL and IADL unmet need stratified by race, ethnicity, and rurality. Our findings show that homebound Veterans are more likely to experience unmet needs and highlight the need for more targeted research on minority Veterans. Overall, this dissertation identified pathways, patterns, and prevalence of LTC needs and unmet needs to provide valuable information to align LTSS with the needs of older adults and those of their caregivers.&nbsp;</p

    Unraveling the Functional Impact of PTMT5-Dependent Alternative Splicing Events and Their Potential for Enhancing Clinical Efficacy

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    The inhibition of the protein arginine methyltransferase PRMT5 reduces the fidelity of the spliceosome leading to increases in aberrant alternative splicing events. Technological advancements have enabled comprehensive analysis of these splice isoforms, revealing dynamic changes to numerous pathways in response to experimental treatments. Despite progress, understanding how aberrant splicing patterns correlate with tumor sensitivity to pharmacological intervention remains unclear. In this work we characterized alternative splicing events induced by PRMT5 inhibition using RNA sequencing across various tumor lineages. We found a multitude of alternative isoforms, predominantly skipped exons, and retained introns, that were determined to be lineage agnostic and PRMT5 dependent. The identified events served as a signature for PRMT5 inhibitor efficacy, observable even in MTAP deleted xenograft models. Additionally, we investigated the functional consequences of PRMT5-dependent alternative splicing on the DNA damage response pathway. We found that PRMT5 regulates the production of key DNA damage pathway proteins, impacting apoptosis, cell cycle, and yH2AX levels across MTAP deleted tumor lineages. These alterations resulted in an additional tumor vulnerability, leading to synergy when the DNA damage master kinase ATR was inhibited.</p

    Exploring Relationship Quality and Psychological Adjustment Among Individuals Undergoing Breast or Prostate Biopsy and Their Romantic Partners

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    Introduction: Breast and prostate cancer have a high survival rate but the stress of undergoing a cancer biopsy for both the patient and their romantic partner (i.e., a dyad) can put individuals at risk for persistent adverse psychological outcomes and influence the relationship. Little is known about how these processes are influenced throughout the cancer continuum for each dyad member.Methods: This study aimed to conduct a secondary analysis of previously collected data in couples who received a malignant biopsy result for breast or prostate cancer compared to those who received a benign result. Dyads completed self-report measures of relationship quality, sexual interest, and psychological adjustment (satisfaction with life, depression) at the time of biopsy, 1-, 6-, and 9-months post-biopsy. The present study examined changes over time of these constructs from biopsy over 9-months using Hierarchical Linear Modeling. Using the Actor-Partner Interdependence Model, we also tested for actor and partner effects in patients and their partners among the same constructs.Results: Aim 1 results indicated that dyads in which the patient underwent a breast biopsy experienced worse psychological adjustment compared to dyads in which the patient underwent a prostate biopsy. Findings also revealed that dyads did not significantly differ in any of the outcome variables over time based on biopsy result. Aim 2 analyses revealed significant actor effects for both dyad members at each timepoint. Among all dyads, partner effects were significant for relationship quality and sexual interest at some of the timepoints but not for psychological adjustment.Discussion: The study provides insight into how relationship quality, sexual interest, and psychological adjustment evolve over time in patient-partner dyads, from time of cancer biopsy to 9-months post-biopsy. These findings contribute to the ways in which we understand the cancer continuum, by focusing on the time of biopsy and the period following disclosure of results, from the vantage point of patients and their partners.</p

    Diversity and Role of Protistan Symbionts of Marine Holobionts under Climate Change

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    The worsening trajectory&nbsp;of anthropogenic ocean warming represents an existential threat to many marine organisms and their associated microbes. To get a better understanding of the diversity and role of protist symbionts in complex marine holobionts ranging from fish to corals, I conducted a set of experiments to get new perspectives on these&nbsp;complex microbial ecosystems in a warming ocean. In Chapter 1, I contextualize the vast diversity and potential roles of microeukaryotic lineages in coral holobionts. In Chapter 2, I used this context to conduct a holistic investigation of the microbiome of a Mediterranean coral across its distribution and show that corals more susceptible to heat-stress tended to harbor a higher abundance of corallicolids. In Chapter 3, genomic and transcriptomic sequencing of an undescribed apicomplexan-related lineage allowed us to generate the first genomic data for a wide-spread lineage of fish-infecting apicomplexans, sister to the corallicolids, which we named the ichthyocolids. The genetic repertoire of the ichthyocolid apicoplast, or relic chloroplast, was distinct from the corallicolids, broadening our understanding of parasite and plastid evolution. In Chapter 4, the single cell ecology of coral bleaching is investigated using a novel single-cell RNA sequencing protocol complemented with metabarcoding. Cell atlases including host and algal symbiont cells were generated for a reef-building coral under heat-stress, showing differential gene expression between different communities of symbionts and coral cell types. Specifically, a &ldquo;front-loading&rdquo; of heat-stress genes was associated with coral cells hosting Durusdinium&nbsp;sp. compared to those hosting Breviolum sp. I conclude with a discussion on the history and future applications of new sequencing technologies to investigate marine holobionts. Through this dissertation, I have broadened our understanding of the marine holobionts, especially their microeukaryotic members, and their fate in a warming ocean.</p

    Proteolysis-targeting chimera (PROTAC) nanomedicines toward cancer treatment: From synthesis to therapeutic delivery

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    Proteolysis-targeting chimera (PROTAC) has emerged as a groundbreaking therapeutic strategy by hijacking the endogenous ubiquitin proteasome system (UPS) for targeted protein degradation. These heterobifunctional molecules recruit E3 ligases to recognize the protein of interest (POI) and facilitate its ubiquitination, leading to subsequent proteasomal degradation. Compared to conventional protein inhibitors, PROTACs offer a broader range of target degradation and remain effective even against proteins with drug-resistant mutations. Moreover, PROTACs function in a catalytic manner to degrade POIs, allowing for significantly lower administration dosages. In recent years, PROTACs have shown great promise in cancer therapy due to their high efficiency and broad applicability. However, their clinical applications remain challenging due to low bioavailability, limited tumor-targeting ability, and potential side effects. Utilizing nanomedicine for the delivery of PROTACs offers a promising strategy to enhance bioavailability, improve tumor selectivity, and minimize toxicity, thereby advancing their applications in cancer treatment. In this review, we outline the fundamental design principles of PROTACs, summarize the latest progress of nanomedicines from molecular design to drug delivery for improved tumor treatment, introduce PROTAC-based combination therapies and emerging design strategies, and discuss current challenges and future prospects of PROTAC nanomedicines toward clinical translation. Proteolysis-targeting chimeras (PROTACs) have garnered increasing attention in cancer treatment due to their exceptional protein degradation efficacy. However, their clinical applications are hindered by challenges such as low bioavailability, limited tumor-targeting capability, and potential off-target effects. The rational design of PROTAC-based nanomedicines holds great promise for overcoming these limitations and advancing their clinical translation. [Display omitted] •This review illustrates the design principles and delivery strategies of PROTACs.•This review highlights the latest advancement of PROAC-based synergistic therapies and novel PROTAC design strategies.•This review summarizes the key challenges and discusses future research direction of PROTAC nanomedicines

    Biomaterials Strategies for Facial Nerve Repair Following Injury

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    Facial paralysis affects 23,000 people annually in the U.S., often resulting from facial nerve damage due to tumors or surgery. The condition significantly impacts quality of life by impairing emotional expression, communication, breathing complications. Current surgical treatments, attempt to reconnect lost nerves but yield inconsistent results due to donor site complications and scarring. There is an urgent need for improved therapies that enhance nerve regeneration and recovery. Biomaterials offer a promising alternative by guiding axonal regrowth without requiring donor tissue. These materials mimic native tissue and can include factors that attract cells to bridge nerve gaps. This study evaluates the regenerative potential of poly(ethylene glycol) (PEG) tubes in a rat model of acute facial nerve injury. Recovery was assessed through facial palsy scoring, electrophysiology, and histological analyses of cellular infiltration and neuromuscular junction integrity. Results showed that PEG tubes promoted faster recovery than autografts at eight weeks post-injury. Electrophysiological assessments revealed no significant differences in muscle action potentials between PEG and autograft repairs. PEG tubes maintained neuromuscular innervation and preserved NMJ morphology comparable to sham conditions. These findings suggest that PEG implantation provides an effective alternative to autografts for facial nerve repair, offering a scalable, off-the-shelf therapeutic option.</p

    Does carnival contribute to crime? Examining the spatiotemporal effects of Mardi Gras on New Orleans Crime Trends (2012–2024)

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    While criminologists have long been interested in how crime varies across space and time, only recently have studies examined how these dynamics intersect to shape crime patterns surrounding mega public events and venues, such as sporting events or concerts. Although this research has generated critical insights into crime patterns surrounding somewhat temporally and geographically discrete public events, we know less about how long-lasting and more spatially distributed public events that draw in droves of tourists to a city, such as Carnival in New Orleans, influence crime. Drawing on routine activities and crime-pattern theories, we use Carnival in New Orleans as a case study for larger issues of crime, tourism, and public events. Employing negative binomial regressions to analyze publicly available data, we assess the temporal (parade days) and spatial (distance to parade routes) effects of Carnival season on daily neighborhood crime patterns from 2012 to 2024 (N = 1,364,330). Compared to non-parade days or parade days earlier in the Carnival season, estimates reveal significant increases in crime rates during Mardi Gras weekend when tourists most often visit New Orleans, particularly in neighborhoods closest to parade routes. Conversely, crime is displaced in New Orleans during Mardi Gras weekend, with neighborhoods farther from parade routes experiencing significant declines in crime. These findings have important theoretical and policy implications for our understanding of crime and mega public events/venues, highlighting the role of tourism in shaping spatiotemporal crime trends.•Crime rates are elevated during Mardi Gras weekend compared to other days.•Crime rates are highest closer to the parade route during Mardi Gras weekend.•Crime displacement occurs during Mardi Gras weekend farther from the parade route.•Despite crime increases on Mardi Gras weekend, Carnival season is relatively safe

    Responsible Machine Learning Deployment: Imperative Framework for Ethical Action

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    The rapid expansion of Machine Learning (ML) across finance, healthcare, education, and public policy makes ethical oversight an imperative rather than an optional add-on. This paper responds to that urgency by proposing a comprehensive framework grounded in ten principles—accuracy, fairness, accessibility, security, privacy, transparency, accountability, human oversight, sustainability, and harm avoidance—and positioning them within existing international guidelines. Recent scoping reviews have highlighted the lack of consistent evaluation frameworks across domains and have called for systematic approaches to fairness, accountability, transparency, and ethics. Motivated by case studies of algorithmic redlining, dataset bias, hallucinations in large language models, and ecological concerns, we develop a weighted scoring rubric with thresholds to diagnose ethical compliance. We demonstrate the rubric through case studies, illustrating how the scores identify deficiencies and guide mitigation. The proposed framework is built upon the EU AI Act, NIST’s AI Risk Management Framework, UNESCO’s recommendations, and the OECD AI Principles. We reflect on AI’s energy footprint and the so-called “nuclear dependence” argument, and conclude with a roadmap for practitioners

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