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PHYTOPLANKTON COMMUNITY SUCCESSION IN RELATION TO SALINITY AND TEMPERATURE ALONG THE WESTERN ANTARCTIC PENINSULA: A FOUR-YEAR STUDY LEVERAGING PARTICIPATORY SCIENCE
No full textIn this dissertation I examined the dynamic seasonal and interannual patterns of phytoplankton communities in the coastal waters of the Western Antarctic Peninsula (WAP). The rapid warming of the WAP has led to significant changes in environmental conditions, yet the impact on phytoplankton communities, particularly in relation to environmental drivers, remains poorly understood. In examining a synthesis of 245 published studies, including 42 key works, I recognized discrepancies in the conclusions regarding observed coastal phytoplankton succession responses to environmental conditions such as changing temperature and salinity that may likely arisen from overly sparse sampling. This highlights the need for coordinated high-frequency sampling to improve understanding of phytoplankton dynamics in response to climate change. I demonstrated the transformative role polar tourism could play in expanding our knowledge (Cusick et al. 2020), showing how data collected aboard expedition vessels can significantly enhance the spatial and temporal resolution of ecological studies in remote regions, while also addressing the critical need for community engagement in advancing polar research. My data were acquired through four 5-month sampling seasons along the WAP (61°S–68°S) through a participatory “citizen” science program, “FjordPhyto”. Using metabarcoding sequencing of samples, I identified 65 phytoplankton taxa across seven major groups revealing high interannual variability in phytoplankton community structure. I investigated how environmental variables, particularly sea surface temperature and salinity, shape phytoplankton succession and community structure. Diatoms dominated early-season cold, salty waters, while mixotrophic species such as dinoflagellates, marine stramenopiles (MAST), and haptophytes increased in richness later in the season with warm and fresh conditions. Diatom species showed high interannual variability with significant correlation to timing, temperature, and salinity, and each season featured a consistent low-salinity assemblage of 4-6 diatom species and 1-2 dinoflagellate species, though the exact combination changed each year. A revised conceptual mandala based on these data shows two possible succession sequences: a main sequence in early season with diatoms or an alternate sequence with cryptophytes and dinoflagellates. This mandala offers insights into community responses to environmental drivers. By integrating traditional and innovative methodologies within a participatory science framework, my dissertation advances understanding of protist biodiversity in the WAP
Towards Safety-aware, Robust, and Efficient Autonomous Vehicle Platforms
No full textAutonomous vehicles (AVs) are poised to revolutionize transportation, enhancing safety, convenience, and efficiency in daily commuting. Powered by advancements in deep learning and computer vision, self-driving cars are evolving into complex, data-driven systems capable of continuous self-improvement.Despite their potential, widespread deployment of this technology faces significant challenges:
(1) Safety: The system must manage diverse traffic scenarios and adhere to established driving conventions.
(2) Robustness: Real-world driving presents unpredictable edge cases that the system must handle effectively.
(3) Efficiency: With limited onboard computational resources constrained by energy requirements, the system must optimize hardware usage while maintaining safety.This dissertation explores approaches to build safe, robust and efficient AV system in both system and algorithm perspectives.
We start from the system level, studying the tail latency characteristics in industrial AV systems and factor in how they impact other desideratas such as utilization and throughput. Inspired by this, we propose a tail latency analysis and we outline multiple system-level design to reduce tail latency across the computing stack, which is proved effective through implementation on the industrial-level AV software framework.
We also build an edge-AV computing model aimed at enhancing the safety and utilization of computing infrastructure.We address safety and robustness challenges at the algorithmic level. The long-tailed distribution of edge cases makes it extremely challenging to improve robustness with limited real-world data. To tackle this, we have developed a safety-critical scenario editing framework using reinforcement learning, which automatically generates diverse edge cases for evaluating driving policies.To enhance closed-loop performance, we have built hierarchical behavior-level simulators that enable real-time, closed-loop agent simulations, ensuring both diversity and accuracy.Our data-driven, learning-based methods eliminate the need for manual rule crafting. Specifically, the imitation learning-based motion planner introduces an innovative heatmap regression architecture to improve performance in challenging edge-case driving scenarios. Additionally, inspired by the recent success of large language models (LLMs), we propose leveraging their reasoning capabilities for driving tasks. By utilizing synthesized data from simulators, we have achieved significant performance improvements
Tissue-specific roles of the miRNA Argonaute ALG-1 in aging C. elegans
No full textThis dissertation investigates the role of the miRNA Argonaute protein ALG-1 in promoting longevity and healthy aging in Caenorhabditis elegans. Previous research indicated that the loss of ALG-1 impairs reproduction and shortens lifespan, but the molecular mechanisms behind these effects remain poorly understood. I demonstrate that ALG-1’s role in longevity is distinct from that in fertility, as depleting ALG-1 in adulthood still reduces lifespan but leaves brood size unchanged. I also describe healthspan phenotypes that are dependent on ALG-1, including intestinal integrity, motility, pharyngeal pumping span, and uterine mass accumulation. As new aging studies report tissue-level impacts of individual factors on longevity, I sought to determine the contributions of ALG-1 from each tissue to these phenotypes. Tissue-specific depletion of alg-1 mRNA only from the intestine or distal tip cells reduces lifespan, intestinal integrity, and motility, while depletion from the neurons seems to preserve intestinal integrity. Analysis of differential RNA expression reveals major transcriptomic changes in the absence of intestinal ALG-1 during adulthood, which point towards a role for ALG-1 in preventing an inappropriate immune response among other interesting pathways that require further exploration. Additional RNA-seq experiments show that neuronal-specific gene expression is unchanged when ALG-1 is added back to the neurons of alg-1 mutants. I uncover that one neuronal gene candidate whose expression is up-regulated upon the loss of ALG-1 is ectopically expressed in the uterine masses of alg-1 mutants, while other neuronal candidates have increased expression specifically in the neurons. This work highlights a critical responsibility of ALG-1 in mitigating the senescent pathologies that are characteristic of aging and raises important questions regarding miRNA-mediated intercellular communication and tissue identity
Adipogenic Effect of Magnolol in Primary Human Pre-Adipocytes With Potential Skin Health and Volumizing Effect.
Full text linkBACKGROUND: Aging is associated with fat atrophy and fibrosis with loss of adipocyte differentiation from preadipocytes. New approaches to this loss involve agents that can renew the proliferative and differentiative capacities of preadipocytes with the aim of creating new healthy adipose tissue that secrete adipokines that positively impact on skin health. MATERIAL & METHODS: We investigated the effect of Magnolol (ML), a naturally derived compound, on human primary pre-adipocyte viability and proliferation as well as adipogenic gene expression and increase in lipid production. Cell proliferation was assessed using fluorescent signaling, and adipocyte differentiation was monitored by following morphological and microscopic changes. RNA purification and real-time PCR were undertaken to examine gene expression changes, and Oil red O staining was used to confirm adipose cell transformation. Adipokine expression, in particular adiponectin quantification, was also undertaken. RESULTS: Magnolol, at a relatively low concentration, demonstrated clear adipogenic activity: with a significant increase in preadipocyte proliferation after 48 h and a significant accumulation of adipocytes as demonstrated by oil red staining. Increased gene expression of PLN1 and FABP4 and a significant increase in adiponectin protein expression was demonstrated. CONCLUSION: Magnolol stimulates preadipocyte proliferation and conversion to adipokine-producing adipocytes. This has the potential for a positive skin health and volumizing effect if used in a topical formulation
Enhanced Osteogenic Differentiation of hMSCs Using BMP@ZIF-8-Loaded GelMA Nanocomposite Hydrogels with Controlled BMP-2 Release.
Full text linkHydrogels are highly versatile materials with immense potential for tissue engineering and regenerative medicine owing to their biocompatibility, tunable mechanical properties, and ability to mimic the natural extracellular matrix. Their 3D porous structure allows for the encapsulation and delivery of bioactive molecules, making them ideal candidates for drug delivery systems. In tissue repair, particularly for bone regeneration, hydrogels can serve as carriers that release therapeutic agents in a controlled manner, thus enhancing the healing process. Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles and recombinant human Bone Morphogenetic Protein (rhBMP-2) molecules were incorporated solely (ZIF@GelMA) or in association (BMP@ZIF@GelMA) into gelatin modified by a methacryloyl hydrogel (GelMA) to investigate its physical and osteogenic properties. Hydrogels were characterized by Scanning Electron Microscopy and rheological tests. We analyzed hydrogel degradation and the BSA release profile of BMP@ZIF@GelMA samples throughout 0, 1, 3, 7, 14, and 28 days. Cell adhesion and bone formation markers were analyzed for hydrogel-encapsulated human dental pulp cells by using immunocytochemistry and molecular analysis. ZIF@GelMA and BMP@ZIF@GelMA exhibited a porous and viscoelastic structure with increased storage modulus when rhBMP2 was present. BSA@ZIF@GelMA showed a balanced degradation rate and a controlled release of BSA. The ZIF@GelMA upregulated the expression of cell adhesion and bone formation genes, and when BMP-2 was introduced, the levels of markers were remarkably elevated. BMP@ZIF@GelMA hydrogel presents several favorable factors to promote cellular adhesion and bone regeneration, thus encouraging further prospects for advanced therapeutic applications in tissue repair
Safe Reuse of Treated Wastewater: Accumulation of Contaminants of Emerging Concern in Field-Grown Vegetables under Different Irrigation Schemes.
Full text linkThe reuse of treated wastewater (TWW) for irrigation alleviates freshwater (FW) scarcity while supporting a circular economy. However, the potential human exposure to contaminants of emerging concern (CECs) through plant accumulation is a significant barrier. Currently, knowledge on CEC contamination of edible produce and effective mitigation strategies for the safe reuse of TWW is limited, particularly under field conditions. This study examined the accumulation of a representative set of CECs, including perfluoroalkyl and polyfluoroalkyl substances (PFAS), pharmaceuticals and personal care products, and tire wear particle (TWP) chemicals, in radish, lettuce, and tomato under three irrigation practices: FULL (continuous TWW irrigation), HALF (midseason switch from TWW to FW), and FW-only. Despite low PFAS concentrations (8.1-25.7 ng/L) in TWW, the plant uptake was consistently observed, including in tomato fruits. Alternating TWW with FW significantly reduced CEC accumulation in edible tissues, particularly for compounds with short half-lives, with reductions up to 82.4% even for persistent PFAS. For most CECs and plant species, edible tissue concentrations were similar between the HALF and FW treatments. These findings demonstrate the on-farm applicability of simple irrigation modifications to reduce food contamination and contribute to the promotion of safe reuse of nonconventional waters
vcfgl: a flexible genotype likelihood simulator for VCF/BCF files.
Full text linkMOTIVATION: Accurate quantification of genotype uncertainty is pivotal in ensuring the reliability of genetic inferences drawn from NGS data. Genotype uncertainty is typically modeled using Genotype Likelihoods (GLs), which can help propagate measures of statistical uncertainty in base calls to downstream analyses. However, the effects of errors and biases in the estimation of GLs, introduced by biases in the original base call quality scores or the discretization of quality scores, as well as the choice of the GL model, remain under-explored. RESULTS: We present vcfgl, a versatile tool for simulating genotype likelihoods associated with simulated read data. It offers a framework for researchers to simulate and investigate the uncertainties and biases associated with the quantification of uncertainty, thereby facilitating a deeper understanding of their impacts on downstream analytical methods. Through simulations, we demonstrate the utility of vcfgl in benchmarking GL-based methods. The program can calculate GLs using various widely used genotype likelihood models and can simulate the errors in quality scores using a Beta distribution. It is compatible with modern simulators such as msprime and SLiM, and can output data in pileup, Variant Call Format (VCF)/BCF, and genomic VCF file formats, supporting a wide range of applications. The vcfgl program is freely available as an efficient and user-friendly software written in C/C++. AVAILABILITY AND IMPLEMENTATION: vcfgl is freely available at https://github.com/isinaltinkaya/vcfgl
County Sales Tax Measures for Transportation Can Affect Regional Plans for Sustainable Transportation
Full text linkIn California, local option sales taxes (LOSTs) are adopted by voters to increase the retail sales tax. Revenues are used to fund specific transportation projects. Meanwhile, metropolitan planning organizations (MPOs) are required by Senate Bill 375 to develop long-range plans to achieve reductions in vehicle miles traveled and emissions. But MPOs do not directly control the sponsorship or funding of most transportation projects in these plans. LOSTs are not bound by requirements of SB 375, even though MPOs must still account for impacts of LOST spending. In this context, an important question is whether and how LOST measures influence transportation planning priorities. To explore this question, researchers from the University of California, Davis, examined county LOST measures and regional transportation plans in California’s “big four” MPO regions—the San Francisco, Los Angeles, San Diego, and Sacramento metropolitan areas. This policy brief summarizes the findings from that research and provides policy implications.
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Neuroprotection for neonatal hypoxic-ischemic encephalopathy: A review of novel therapies evaluated in clinical studies.
Full text linkTherapeutic hypothermia is an effective therapy for moderate-to-severe hypoxic-ischemic encephalopathy (HIE) in infants born at term or near-term in high-resource settings. Yet there remains a substantial proportion of infants who do not benefit or who will have significant disability despite therapeutic hypothermia. Novel investigational therapies that may confer additional neuroprotection by targeting known pathogenic mechanisms of hypoxic-ischemic brain injury are under development. This review focuses on putative neuroprotective agents that have shown promise in animal models of HIE, and that have been translated to clinical studies in neonates with HIE. We include agents that have been studied both with and without concurrent therapeutic hypothermia. Our review therefore addresses not just neonatal HIE in high-resource countries where therapeutic hypothermia is the standard of care, but also neonatal HIE in low- and middle-income countries where therapeutic hypothermia has been shown to be ineffective, and where the greatest burden of HIE-related morbidity and mortality exists
Real-world evaluation of teclistamab for the treatment of relapsed/refractory multiple myeloma (RRMM): an International Myeloma Working Group Study.
Full text linkTeclistamab, a BCMAxCD3-directed bispecific antibody, has shown high response rates and durable remissions in triple-class-exposed patients with relapsed/refractory multiple myeloma. We performed a retrospective study evaluating the efficacy and safety of teclistamab in 210 patients treated at 9 academic centers from five countries within the IMWG Immunotherapy Working Group Committee. Patients were heavily pretreated, with 83% having triple-class refractory disease and 44% with prior BCMA-targeted therapy. With a median follow-up of 5.3 months, the overall response rate (ORR) was 67% in 188 response-evaluable patients, including 55% with a very good partial response or better. The 6-month progression-free survival (PFS) and overall survival rates were 53% (95% CI, 46-61%) and 73% (67-80%), respectively. Patients who received prior BCMA-directed therapy compared to BCMA-treatment-naïve patients had a lower ORR (58.3 vs 74.0%; P = 0.03) and PFS (6-month PFS 43% [95% CI, 33-55%] vs 63% [54-73%]; logrank P = 0.004). Step-up dosing occurred in an outpatient setting for 23% of patients. CRS occurred in 54% of patients, and infections were reported in 56.2% of patients, with 22% having grade ≥3 infections. In this multicenter real-world study, we found that teclistamab can lead to rapid responses in heavily pretreated myeloma patients with comparable efficacy and safety profiles, as demonstrated in MajesTEC-1