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  1. Abstract Recent progress in the field of micron-scale spatial resolution direct conversion X-ray detectors for high-energy synchrotron light sources serve applications ranging from nondestructive and noninvasive microscopy techniques which provide insight into the structure and morphology of crystals, to medical diagnostic measurement devices. Amorphous selenium ( a -Se) as a wide-bandgap thermally evaporated photoconductor exhibits ultra-low thermal generation rates for dark carriers and has been extensively used in X-ray medical imaging. Being an amorphous material, it can further be deposited over large areas at room temperatures and at substantially lower costs as compared to crystalline semiconductors. To address the demands for a high-energy and high spatial resolution X-ray detector for synchrotron light source applications, we have thermally evaporated a -Se on a Mixed-Mode Pixel Array Detector (MM-PAD) Application Specific Integrated Circuit (ASIC). The ASIC format consists of 128 × 128 square pixels each 150 μm on a side. A 200 μm a -Se layer was directly deposited on the ASIC followed by a metal top electrode. The completed detector assembly was tested with 45 kV Ag and 23 kV Cu X-ray tube sources. The detector fabrication, performances, Modulation Transfer Function (MTF) measurements, and simulations are reported.
    Free, publicly-accessible full text available April 1, 2024
  2. Abstract There is definitive evidence that microplastics, defined as plastic particles less than 5 mm in size, are ubiquitous in the environment and can cause harm to aquatic organisms. These findings have prompted legislators and environmental regulators to seek out strategies for managing risk. However, microplastics are also an incredibly diverse contaminant suite, comprising a complex mixture of physical and chemical characteristics (e.g., sizes, morphologies, polymer types, chemical additives, sorbed chemicals, and impurities), making it challenging to identify which particle characteristics might influence the associated hazards to aquatic life. In addition, there is a lack of consensus on how microplastic concentrations should be reported. This not only makes it difficult to compare concentrations across studies, but it also begs the question as to which concentration metric may be most informative for hazard characterization. Thus, an international panel of experts was convened to identify 1) which concentration metrics (e.g., mass or count per unit of volume or mass) are most informative for the development of health-based thresholds and risk assessment and 2) which microplastic characteristics best inform toxicological concerns. Based on existing knowledge, it is recommended that microplastic concentrations in toxicity tests are calculated from both mass and count at minimum, thoughmore »ideally researchers should report additional metrics, such as volume and surface area, which may be more informative for specific toxicity mechanisms. Regarding particle characteristics, there is sufficient evidence to conclude that particle size is a critical determinant of toxicological outcomes, particularly for the mechanisms of food dilution and tissue translocation .« less
    Free, publicly-accessible full text available December 1, 2023
  3. Abstract Microplastic particles (MPs) are ubiquitous across a wide range of aquatic habitats but determining an appropriate level of risk management is hindered by a poor understanding of environmental risk. Here, we introduce a risk management framework for aquatic ecosystems that identifies four critical management thresholds, ranging from low regulatory concern to the highest level of concern where pollution control measures could be introduced to mitigate environmental emissions. The four thresholds were derived using a species sensitivity distribution (SSD) approach and the best available data from the peer-reviewed literature. This included a total of 290 data points extracted from 21 peer-reviewed microplastic toxicity studies meeting a minimal set of pre-defined quality criteria. The meta-analysis resulted in the development of critical thresholds for two effects mechanisms: food dilution with thresholds ranging from ~ 0.5 to 35 particles/L, and tissue translocation with thresholds ranging from ~ 60 to 4100 particles/L. This project was completed within an expert working group, which assigned high confidence to the management framework and associated analytical approach for developing thresholds, and very low to high confidence in the numerical thresholds. Consequently, several research recommendations are presented, which would strengthen confidence in quantifying threshold values for use in risk assessment andmore »management. These recommendations include a need for high quality toxicity tests, and for an improved understanding of the mechanisms of action to better establish links to ecologically relevant adverse effects.« less
    Free, publicly-accessible full text available December 1, 2023
  4. The phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family of lipid-modifying enzymes generate the majority of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] lipids found at the plasma membrane in eukaryotic cells. PI(4,5)P 2 lipids serve a critical role in regulating receptor activation, ion channel gating, endocytosis, and actin nucleation. Here, we describe how PIP5K activity is regulated by cooperative binding to PI(4,5)P 2 lipids and membrane-mediated dimerization of the kinase domain. In contrast to constitutively dimeric phosphatidylinositol 5-phosphate 4-kinase (PIP4K, type II PIPK), solution PIP5K exists in a weak monomer–dimer equilibrium. PIP5K monomers can associate with PI(4,5)P 2 -containing membranes and dimerize in a protein density-dependent manner. Although dispensable for cooperative PI(4,5)P 2 binding, dimerization enhances the catalytic efficiency of PIP5K through a mechanism consistent with allosteric regulation. Additionally, dimerization amplifies stochastic variation in the kinase reaction velocity and strengthens effects such as the recently described stochastic geometry sensing. Overall, the mechanism of PIP5K membrane binding creates a broad dynamic range of lipid kinase activities that are coupled to the density of PI(4,5)P 2 and membrane-bound kinase.
    Free, publicly-accessible full text available August 17, 2023
  5. Abstract Throughout the past decade, many studies have reported adverse effects in biota following microplastic exposure. Yet, the field is still emerging as the current understanding of microplastic toxicity is limited. At the same time, recent legislative mandates have required environmental regulators to devise strategies to mitigate microplastic pollution and develop health-based thresholds for the protection of human and ecosystem health. The current publication rate also presents a unique challenge as scientists, environmental managers, and other communities may find it difficult to keep up with microplastic research as it rapidly evolves. At present, there is no tool that compiles and synthesizes the data from these studies to allow for visualization, interpretation, or analysis. Here, we present the Toxicity of Microplastics Explorer (ToMEx), an open access database and open source accompanying R Shiny web application that enables users to upload, search, visualize, and analyze microplastic toxicity data. Though ToMEx was originally created to facilitate the development of health-based thresholds to support California legislations, maintaining the database by the greater scientific community will be invaluable to furthering research and informing policies globally. The database and web applications may be accessed at . Graphical Abstract
    Free, publicly-accessible full text available December 1, 2023
  6. Abstract

    Microplastics have been documented in drinking water, but their effects on human health from ingestion, or the concentrations at which those effects begin to manifest, are not established. Here, we report on the outcome of a virtual expert workshop conducted between October 2020 and October 2021 in which a comprehensive review of mammalian hazard studies was conducted. A key objective of this assessment was to evaluate the feasibility and confidence in deriving a human health-based threshold value to inform development of the State of California’s monitoring and management strategy for microplastics in drinking water. A tiered approach was adopted to evaluate the quality and reliability of studies identified from a review of the peer-reviewed scientific literature. A total of 41 in vitro and 31 in vivo studies using mammals were identified and subjected to a Tier 1 screening and prioritization exercise, which was based on an evaluation of how each of the studies addressed various quality criteria. Prioritized studies were identified largely based on their application and reporting of dose–response relationships. Given that methods for extrapolating between in vitro and in vivo systems are currently lacking, only oral exposure in vivo studies were identified as fit-for-purpose within the contextmore »of this workshop. Twelve mammalian toxicity studies were prioritized and subjected to a Tier 2 qualitative evaluation by external experts. Of the 12 studies, 7 report adverse effects on male and female reproductive systems, while 5 reported effects on various other physiological endpoints. It is notable that the majority of studies (83%) subjected to Tier 2 evaluation report results from exposure to a single polymer type (polystyrene spheres), representing a size range of 0.040 to 20 µm. No single study met all desired quality criteria, but collectively toxicological effects with respect to biomarkers of inflammation and oxidative stress represented a consistent trend. While it was possible to derive a conservative screening level to inform monitoring activities, it was not possible to extrapolate a human–health-based threshold value for microplastics, which is largely due to concerns regarding the relative quality and reliability of current data, but also due to the inability to extrapolate data from studies using monodisperse plastic particles, such as polystyrene spheres to an environmentally relevant exposure of microplastics. Nevertheless, a conservative screening level value was used to estimate a volume of drinking water (1000 L) that could be used to support monitoring activities and improve our overall understanding of exposure in California’s drinking water. In order to increase confidence in our ability to derive a human–health-based threshold value in the future, several research recommendations are provided, with an emphasis towards strengthening how toxicity studies should be conducted in the future and an improved understanding of human exposure to microplastics, insights critically important to better inform future risk assessments.

    Graphical abstract

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