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Showing papers by "Oregon State University published in 2021"


Journal ArticleDOI
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

1,129 citations


Journal ArticleDOI
25 Mar 2021-Nature
TL;DR: A review of the development of aquaculture from 1997 to 2017 can be found in this article, where the authors highlight the integration of aqua-culture in the global food system and the potential for molluscs and seaweed to support global nutritional security.
Abstract: The sustainability of aquaculture has been debated intensely since 2000, when a review on the net contribution of aquaculture to world fish supplies was published in Nature. This paper reviews the developments in global aquaculture from 1997 to 2017, incorporating all industry sub-sectors and highlighting the integration of aquaculture in the global food system. Inland aquaculture—especially in Asia—has contributed the most to global production volumes and food security. Major gains have also occurred in aquaculture feed efficiency and fish nutrition, lowering the fish-in–fish-out ratio for all fed species, although the dependence on marine ingredients persists and reliance on terrestrial ingredients has increased. The culture of both molluscs and seaweed is increasingly recognized for its ecosystem services; however, the quantification, valuation, and market development of these services remain rare. The potential for molluscs and seaweed to support global nutritional security is underexploited. Management of pathogens, parasites, and pests remains a sustainability challenge industry-wide, and the effects of climate change on aquaculture remain uncertain and difficult to validate. Pressure on the aquaculture industry to embrace comprehensive sustainability measures during this 20-year period have improved the governance, technology, siting, and management in many cases. The volume of global aquaculture production has tripled since 2000 with positive trends in environmental performance, but the sector faces mounting challenges including pathogen management, pollution, climate change, and increasing dependence on land-based resource systems.

618 citations


Journal ArticleDOI
05 Feb 2021-Science
TL;DR: In this article, a clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-programmed cell death protein 1 (PD-1) therapy for patients with advanced melanoma.
Abstract: Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma

540 citations


Journal ArticleDOI
TL;DR: Recent major extensions of the Human Phenotype Ontology for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas are presented and new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease are presented.
Abstract: The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.

503 citations


Journal ArticleDOI
07 Jan 2021-PLOS ONE
TL;DR: It was showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously.
Abstract: Background University students are increasingly recognized as a vulnerable population, suffering from higher levels of anxiety, depression, substance abuse, and disordered eating compared to the general population. Therefore, when the nature of their educational experience radically changes—such as sheltering in place during the COVID-19 pandemic—the burden on the mental health of this vulnerable population is amplified. The objectives of this study are to 1) identify the array of psychological impacts COVID-19 has on students, 2) develop profiles to characterize students' anticipated levels of psychological impact during the pandemic, and 3) evaluate potential sociodemographic, lifestyle-related, and awareness of people infected with COVID-19 risk factors that could make students more likely to experience these impacts. Methods Cross-sectional data were collected through web-based questionnaires from seven U.S. universities. Representative and convenience sampling was used to invite students to complete the questionnaires in mid-March to early-May 2020, when most coronavirus-related sheltering in place orders were in effect. We received 2,534 completed responses, of which 61% were from women, 79% from non-Hispanic Whites, and 20% from graduate students. Results Exploratory factor analysis on close-ended responses resulted in two latent constructs, which we used to identify profiles of students with latent profile analysis, including high (45% of sample), moderate (40%), and low (14%) levels of psychological impact. Bivariate associations showed students who were women, were non-Hispanic Asian, in fair/poor health, of below-average relative family income, or who knew someone infected with COVID-19 experienced higher levels of psychological impact. Students who were non-Hispanic White, above-average social class, spent at least two hours outside, or less than eight hours on electronic screens were likely to experience lower levels of psychological impact. Multivariate modeling (mixed-effects logistic regression) showed that being a woman, having fair/poor general health status, being 18 to 24 years old, spending 8 or more hours on screens daily, and knowing someone infected predicted higher levels of psychological impact when risk factors were considered simultaneously. Conclusion Inadequate efforts to recognize and address college students’ mental health challenges, especially during a pandemic, could have long-term consequences on their health and education.

444 citations


Journal ArticleDOI
TL;DR: This paper recommends a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services.
Abstract: Freshwater ecosystems provide irreplaceable services for both nature and society. The quality and quantity of freshwater affect biogeochemical processes and ecological dynamics that determine biodiversity, ecosystem productivity, and human health and welfare at local, regional and global scales. Freshwater ecosystems and their associated riparian habitats are amongst the most biologically diverse on Earth, and have inestimable economic, health, cultural, scientific and educational values. Yet human impacts to lakes, rivers, streams, wetlands and groundwater are dramatically reducing biodiversity and robbing critical natural resources and services from current and future generations. Freshwater biodiversity is declining rapidly on every continent and in every major river basin on Earth, and this degradation is occurring more rapidly than in terrestrial ecosystems. Currently, about one third of all global freshwater discharges pass through human agricultural, industrial or urban infrastructure. About one fifth of the Earth's arable land is now already equipped for irrigation, including all the most productive lands, and this proportion is projected to surpass one third by midcentury to feed the rapidly expanding populations of humans and commensal species, especially poultry and ruminant livestock. Less than one fifth of the world's preindustrial freshwater wetlands remain, and this proportion is projected to decline to under one tenth by midcentury, with imminent threats from water transfer megaprojects in Brazil and India, and coastal wetland drainage megaprojects in China. The Living Planet Index for freshwater vertebrate populations has declined to just one third that of 1970, and is projected to sink below one fifth by midcentury. A linear model of global economic expansion yields the chilling prediction that human utilization of critical freshwater resources will approach one half of the Earth's total capacity by midcentury. Although the magnitude and growth of the human freshwater footprint are greater than is generally understood by policy makers, the news media, or the general public, slowing and reversing dramatic losses of freshwater species and ecosystems is still possible. We recommend a set of urgent policy actions that promote clean water, conserve watershed services, and restore freshwater ecosystems and their vital services. Effective management of freshwater resources and ecosystems must be ranked amongst humanity's highest priorities.

325 citations


Journal ArticleDOI
TL;DR: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics.

298 citations


Journal ArticleDOI
17 Mar 2021-Nature
TL;DR: In this paper, a conservation planning framework is developed to prioritize highly protected marine protected areas in places that would result in multiple benefits today and in the future, by protecting biodiversity, boosting the yield of fisheries and securing marine carbon stocks that are at risk from human activities.
Abstract: The ocean contains unique biodiversity, provides valuable food resources and is a major sink for anthropogenic carbon. Marine protected areas (MPAs) are an effective tool for restoring ocean biodiversity and ecosystem services1,2, but at present only 2.7% of the ocean is highly protected3. This low level of ocean protection is due largely to conflicts with fisheries and other extractive uses. To address this issue, here we developed a conservation planning framework to prioritize highly protected MPAs in places that would result in multiple benefits today and in the future. We find that a substantial increase in ocean protection could have triple benefits, by protecting biodiversity, boosting the yield of fisheries and securing marine carbon stocks that are at risk from human activities. Our results show that most coastal nations contain priority areas that can contribute substantially to achieving these three objectives of biodiversity protection, food provision and carbon storage. A globally coordinated effort could be nearly twice as efficient as uncoordinated, national-level conservation planning. Our flexible prioritization framework could help to inform both national marine spatial plans4 and global targets for marine conservation, food security and climate action. Using a globally coordinated strategic conservation framework to plan an increase in ocean protection through marine protected areas can yield benefits for biodiversity, food provisioning and carbon storage.

265 citations


Journal ArticleDOI
04 Feb 2021
TL;DR: Deep learning approaches to anomaly detection (AD) have recently improved the state of the art in detection performance on complex data sets, such as large collections of images or text as mentioned in this paper, and led to the introduction of a great variety of new methods.
Abstract: Deep learning approaches to anomaly detection (AD) have recently improved the state of the art in detection performance on complex data sets, such as large collections of images or text. These results have sparked a renewed interest in the AD problem and led to the introduction of a great variety of new methods. With the emergence of numerous such methods, including approaches based on generative models, one-class classification, and reconstruction, there is a growing need to bring methods of this field into a systematic and unified perspective. In this review, we aim to identify the common underlying principles and the assumptions that are often made implicitly by various methods. In particular, we draw connections between classic “shallow” and novel deep approaches and show how this relation might cross-fertilize or extend both directions. We further provide an empirical assessment of major existing methods that are enriched by the use of recent explainability techniques and present specific worked-through examples together with practical advice. Finally, we outline critical open challenges and identify specific paths for future research in AD.

257 citations


Journal ArticleDOI
TL;DR: The workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked as discussed by the authors, but the workflows can also be difficult to adapt to real-world applications.
Abstract: Big data abound in microbiology, but the workflows designed to enable researchers to interpret data can constrain the biological questions that can be asked. Five years after anvi’o was first published, this community-led multi-omics platform is maturing into an open software ecosystem that reduces constraints in ‘omics data analyses.

220 citations


Journal ArticleDOI
TL;DR: In this article, the authors discuss non-metallic charge carriers for aqueous batteries, investigating fundamental mechanisms of charge storage and electrode interactions, as well as battery design and performance.
Abstract: Charge carriers are fundamental components of batteries that determine battery chemistry and performance. Non-metallic charge carriers provide an alternative to metallic charge carriers in aqueous batteries, enabling fast kinetics, long cyclic lifetime and low manufacturing costs. Non-metallic charge carriers not only can be inserted into the electrode framework, where they establish covalent–ionic bonds, but can also serve as reversible redox centres for charge transfer, resulting in superior performance compared with metallic charge carrier-based devices. In this Review, we discuss cationic and anionic non-metallic charge carriers, their physicochemical properties, charge storage mechanisms and electrode interactions. We examine battery configurations of non-metallic charge carrier-based devices and analyse battery performance based on costs, capacity, working potential, rate capability and cycling stability. Finally, we highlight design strategies for aqueous batteries based on non-metallic charge carriers and future applications. This Review discusses non-metallic charge carriers for aqueous batteries, investigating fundamental mechanisms of charge storage and electrode interactions, as well as battery design and performance.

Journal ArticleDOI
13 Jan 2021
TL;DR: The scale of the threats to the biosphere and all its lifeforms is in fact so great that it is difficult to grasp for even well-informed experts as mentioned in this paper, and this dire situation places an extraordinary responsibility on scientists to speak out candidly and accurately when engaging with government, business, and the public.
Abstract: We report three major and confronting environmental issues that have received little attention and require urgent action. First, we review the evidence that future environmental conditions will be far more dangerous than currently believed. The scale of the threats to the biosphere and all its lifeforms — including humanity — is in fact so great that it is difficult to grasp for even well-informed experts. Second, we ask what political or economic system, or leadership, is prepared to handle the predicted disasters, or even capable of such action. Third, this dire situation places an extraordinary responsibility on scientists to speak out candidly and accurately when engaging with government, business, and the public. We especially draw attention to the lack of appreciation of the enormous challenges to creating a sustainable future. The added stresses to human health, wealth, and well-being will perversely diminish our political capacity to mitigate the erosion of ecosystem services on which society depends. The science underlying these issues is strong, but awareness is weak. Without fully appreciating and broadcasting the scale of the problems and the enormity of the solutions required, society will fail to achieve even modest sustainability goals.

Journal ArticleDOI
01 Jun 2021
TL;DR: A review of the mechanisms and processes operating at the mineral-organic interface as they relate to OM transformation dynamics can be found in this paper, where a broad set of interactions occur, with minerals adsorbing organic compounds to their surfaces and acting as catalysts for organic reactions.
Abstract: Minerals are widely assumed to protect organic matter (OM) from degradation in the environment, promoting the persistence of carbon in soil and sediments. In this Review, we describe the mechanisms and processes operating at the mineral–organic interface as they relate to OM transformation dynamics. A broad set of interactions occur, with minerals adsorbing organic compounds to their surfaces and/or acting as catalysts for organic reactions. Minerals can serve as redox partners for OM through direct electron transfer or by generating reactive oxygen species, which then oxidize OM. Finally, the compartmentalization of soil and sediment by minerals creates unique microsites that host diverse microbial communities. Acknowledgement of this multiplicity of interactions suggests that the general assumption that the mineral matrix provides a protective function for OM is overly simplistic. Future work must recognize adsorption as a condition for further reactions instead of as a final destination for organic adsorbates, and should consider the spatial and functional complexity that is characteristic of the environments where mineral–OM interactions are observed.

Journal ArticleDOI
Jens H. Kuhn1, Scott Adkins2, Daniela Alioto3, S. V. Alkhovsky4  +231 moreInstitutions (125)
TL;DR: The updated taxonomy of Negarnaviricota is presented, as now accepted by the ICTV, after the phylum was amended and emended in March 2020.
Abstract: In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Journal ArticleDOI
TL;DR: In this article, a review of the design and self-assembly of mRNA vaccines is presented, highlighting the materials commonly utilized to deliver mRNA, their physicochemical characteristics, and other relevant considerations, such as mRNA optimization, routes of administration, cellular fate, and immune activation, that are important for successful mRNA vaccination.

Journal ArticleDOI
TL;DR: A systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic is provided in this paper.
Abstract: The COVID-19 pandemic has exposed an interconnected and tightly coupled globalized world in rapid change. This article sets the scientific stage for understanding and responding to such change for global sustainability and resilient societies. We provide a systemic overview of the current situation where people and nature are dynamically intertwined and embedded in the biosphere, placing shocks and extreme events as part of this dynamic; humanity has become the major force in shaping the future of the Earth system as a whole; and the scale and pace of the human dimension have caused climate change, rapid loss of biodiversity, growing inequalities, and loss of resilience to deal with uncertainty and surprise. Taken together, human actions are challenging the biosphere foundation for a prosperous development of civilizations. The Anthropocene reality—of rising system-wide turbulence—calls for transformative change towards sustainable futures. Emerging technologies, social innovations, broader shifts in cultural repertoires, as well as a diverse portfolio of active stewardship of human actions in support of a resilient biosphere are highlighted as essential parts of such transformations.

Journal ArticleDOI
TL;DR: In this paper, a universal strategy is proposed to overcome the anode instability issues by rationally designing alloyed materials, using Zn-M alloys as model systems (M = Mn and other transition metals).
Abstract: Metal anode instability, including dendrite growth, metal corrosion, and hetero-ions interference, occurring at the electrolyte/electrode interface of aqueous batteries, are among the most critical issues hindering their widespread use in energy storage. Herein, a universal strategy is proposed to overcome the anode instability issues by rationally designing alloyed materials, using Zn-M alloys as model systems (M = Mn and other transition metals). An in-situ optical visualization coupled with finite element analysis is utilized to mimic actual electrochemical environments analogous to the actual aqueous batteries and analyze the complex electrochemical behaviors. The Zn-Mn alloy anodes achieved stability over thousands of cycles even under harsh electrochemical conditions, including testing in seawater-based aqueous electrolytes and using a high current density of 80 mA cm−2. The proposed design strategy and the in-situ visualization protocol for the observation of dendrite growth set up a new milestone in developing durable electrodes for aqueous batteries and beyond. Metal anode instability due to several intrinsic factors limits their widespread use in energy storage. Here, the authors report a 3D alloy anode via a universal alloy electrodeposition approach to overcome the anode instability issues and demonstrate a seawater-based aqueous battery.

Journal ArticleDOI
Lawrence Berkeley National Laboratory1, National University of Singapore2, Stanford University3, National Ecological Observatory Network4, University of Wisconsin-Madison5, Oak Ridge National Laboratory6, McMaster University7, University of Nebraska–Lincoln8, University of California, Berkeley9, Agricultural Research Service10, University of British Columbia11, University of Colorado Boulder12, Ohio State University13, University of Florida14, University of Guelph15, University of Kansas16, Michigan State University17, Pacific Northwest National Laboratory18, United States Department of Agriculture19, University of New Mexico20, National Research Council21, Marine Biological Laboratory22, University of Alberta23, Virginia Commonwealth University24, University of Minnesota25, Dalhousie University26, Université de Montréal27, Carleton University28, Shinshu University29, Japan Agency for Marine-Earth Science and Technology30, Northern Arizona University31, Oregon State University32, Yale University33, Washington State University34, Harvard University35, Texas A&M University36, Indiana University37, Florida International University38, San Diego State University39, California State University, East Bay40, Wayne State University41, University of Sydney42, Wilfrid Laurier University43, University of Alabama44, Environment Canada45, United States Geological Survey46, Argonne National Laboratory47, Osaka Prefecture University48, University of Delaware49, University of Missouri50, University of Sheffield51
TL;DR: In this article, the authors evaluate the representativeness of flux footprints and evaluate potential biases as a consequence of the footprint-to-target-area mismatch, which can be used as a guide to identify site-periods suitable for specific applications.

Journal ArticleDOI
TL;DR: In this paper, the authors present a 2020 battery technology roadmap for renewable energy generation, focusing on various kinds of batteries to store energy, such as lithium-related batteries, sodium-related, zinc-related and aluminum-related.
Abstract: Sun, wind and tides have huge potential in providing us electricity in an environmental-friendly way. However, its intermittency and non-dispatchability are major reasons preventing full-scale adoption of renewable energy generation. Energy storage will enable this adoption by enabling a constant and high-quality electricity supply from these systems. But which storage technology should be considered is one of important issues. Nowadays, great effort has been focused on various kinds of batteries to store energy, lithium-related batteries, sodium-related batteries, zinc-related batteries, aluminum-related batteries and so on. Some cathodes can be used for these batteries, such as sulfur, oxygen, layered compounds. In addition, the construction of these batteries can be changed into flexible, flow or solid-state types. There are many challenges in electrode materials, electrolytes and construction of these batteries and research related to the battery systems for energy storage is extremely active. With the myriad of technologies and their associated technological challenges, we were motivated to assemble this 2020 battery technology roadmap.

Journal ArticleDOI
TL;DR: CNN Explainer is an interactive visualization tool designed for non-experts to learn and examine convolutional neural networks, a foundational deep learning model architecture, and is engaging and enjoyable to use.
Abstract: Deep learning's great success motivates many practitioners and students to learn about this exciting technology. However, it is often challenging for beginners to take their first step due to the complexity of understanding and applying deep learning. We present CNN E xplainer, an interactive visualization tool designed for non-experts to learn and examine convolutional neural networks (CNNs), a foundational deep learning model architecture. Our tool addresses key challenges that novices face while learning about CNNs, which we identify from interviews with instructors and a survey with past students. CNN E xplainer tightly integrates a model overview that summarizes a CNN's structure, and on-demand, dynamic visual explanation views that help users understand the underlying components of CNNs. Through smooth transitions across levels of abstraction, our tool enables users to inspect the interplay between low-level mathematical operations and high-level model structures. A qualitative user study shows that CNN E xplainer helps users more easily understand the inner workings of CNNs, and is engaging and enjoyable to use. We also derive design lessons from our study. Developed using modern web technologies, CNN E xplainer runs locally in users' web browsers without the need for installation or specialized hardware, broadening the public's education access to modern deep learning techniques.

Journal ArticleDOI
TL;DR: In this article, the authors discuss the core features of lipid vesicles for RNA delivery and focus on LNPs designed to deliver mRNA; however, they also include examples of siRNA-LNP delivery where appropriate to highlight the commonalities and dissimilarities due to the nucleic acid structure.
Abstract: ConspectusLipid nanoparticles (LNPs) are a type of lipid vesicles that possess a homogeneous lipid core. These vesicles are widely used in small-molecule drug and nucleic acid delivery and recently gained much attention because of their remarkable success as a delivery platform for COVID-19 mRNA vaccines. Nonetheless, the utility of transient protein expression induced by mRNA extends far beyond vaccines against infectious diseases─they also hold promise as cancer vaccines, protein replacement therapies, and gene editing components for rare genetic diseases. However, naked mRNA is inherently unstable and prone to rapid degradation by nucleases and self-hydrolysis. Encapsulation of mRNA within LNPs protects mRNA from extracellular ribonucleases and assists with intracellular mRNA delivery.In this Account, we discuss the core features of LNPs for RNA delivery. We focus our attention on LNPs designed to deliver mRNA; however, we also include examples of siRNA-LNP delivery where appropriate to highlight the commonalities and the dissimilarities due to the nucleic acid structure. First, we introduce the concept of LNPs, the advantages and disadvantages of utilizing nucleic acids as therapeutic agents, and the general reasoning behind the molecular makeup of LNPs. We also briefly highlight the most recent clinical successes of LNP-based nucleic acid therapies. Second, we describe the theory and methods of LNP self-assembly. The common idea behind all of the preparation methods is inducing electrostatic interactions between the nucleic acid and charged lipids and promoting nanoparticle growth via hydrophobic interactions. Third, we break down the LNP composition with special attention to the fundamental properties and purposes of each component. This includes the identified molecular design criteria, commercial sourcing, impact on intracellular trafficking, and contribution to the properties of LNPs. One of the key components of LNPs is ionizable lipids, which initiate electrostatic binding with endosomal membranes and facilitate cytosolic release; however, the roles of other lipid components should not be disregarded, as they are associated with stability, clearance, and distribution of LNPs. Fourth, we review the attributes of LNP constructs as a whole that can heavily influence RNA delivery. These attributes are LNP size, charge, internal structure, lipid packing, lipid membrane hydration, stability, and affinity toward biomacromolecules. We also discuss the specific techniques used to examine these attributes and how they can be adjusted. Finally, we offer our perspective on the future of RNA therapies and some questions that remain in the realm of LNP formulation and optimization.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness.
Abstract: In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

Journal ArticleDOI
10 Sep 2021-Science
TL;DR: In this article, the authors describe MPAs as conservation tools intended to protect biodiversity, promote healthy and resilient marine ecosystems, and provide societal benefits, despite codification of MPAs.
Abstract: Marine Protected Areas (MPAs) are conservation tools intended to protect biodiversity, promote healthy and resilient marine ecosystems, and provide societal benefits. Despite codification of MPAs i...

Journal ArticleDOI
TL;DR: In 2018, the 25th year of development of radar altimetry was celebrated and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences as discussed by the authors.

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TL;DR: A robust phylogenomic framework to explore the tempo and mode of fungal evolution and offer directions for future fungal phylogenetic and taxonomic studies is provided.

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TL;DR: In this article, an iridium single atom on Ni2P catalyst (IrSA-Ni2P) with a record low overpotential of 149 mV at a current density of 10 mA·cm-2 in 1.0 M KOH was reported.
Abstract: Single-atom catalysts (SACs) with 100% active sites have excellent prospects for application in the oxygen evolution reaction (OER). However, further enhancement of the catalytic activity for OER is quite challenging, particularly for the development of stable SACs with overpotentials <180 mV. Here, we report an iridium single atom on Ni2P catalyst (IrSA-Ni2P) with a record low overpotential of 149 mV at a current density of 10 mA·cm-2 in 1.0 M KOH. The IrSA-Ni2P catalyst delivers a current density up to ∼28-fold higher than that of the widely used IrO2 at 1.53 V vs RHE. Both the experimental results and computational simulations indicate that Ir single atoms preferentially occupy Ni sites on the top surface. The reconstructed Ir-O-P/Ni-O-P bonding environment plays a vital role for optimal adsorption and desorption of the OER intermediate species, which leads to marked enhancement of the OER activity. Additionally, the dynamic "top-down" evolution of the specific structure of the Ni@Ir particles is responsible for the robust single-atom structure and, thus, the stability property. This IrSA-Ni2P catalyst offers novel prospects for simplifying decoration strategies and further enhancing OER performance.

Journal ArticleDOI
Stuart J. Davies1, Iveren Abiem2, Kamariah Abu Salim3, Salomón Aguilar1  +156 moreInstitutions (79)
TL;DR: ForestGEO as discussed by the authors is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types, which together provide a holistic view of forest functioning.

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TL;DR: In this article, high-density single-atom catalysts for an oxygen evolution reaction (OER) supported by CoOx amorporation have been proposed for renewable energy storage.
Abstract: Developing efficient electrocatalysts for an oxygen evolution reaction (OER) is important for renewable energy storage. Here, we design high-density Ir single-atom catalysts supported by CoOx amorp...

Journal ArticleDOI
B. Abi1, R. Acciarri2, M. A. Acero3, George Adamov4  +979 moreInstitutions (156)
TL;DR: Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.
Abstract: The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

Journal ArticleDOI
TL;DR: Using a Fe-N-C model catalyst derived from the ZIF-8, three key morphological and structural elements of FeN 4 sites are deconvoluted, including particle sizes of catalysts, Fe content, andFe-N bond structures, which elucidated the origin of intrinsic activity improvement associated with the optimal local strain on the Fe- N bond.
Abstract: Atomically dispersed FeN4 active sites have exhibited exceptional catalytic activity and selectivity for the electrochemical CO2 reduction reaction (CO2RR) to CO. However, the understanding behind the intrinsic and morphological factors contributing to the catalytic properties of FeN4 sites is still lacking. By using a Fe-N-C model catalyst derived from the ZIF-8, we deconvoluted three key morphological and structural elements of FeN4 sites, including particle sizes of catalysts, Fe content, and Fe-N bond structures. Their respective impacts on the CO2RR were comprehensively elucidated. Engineering the particle size and Fe doping is critical to control extrinsic morphological factors of FeN4 sites for optimal porosity, electrochemically active surface areas, and the graphitization of the carbon support. In contrast, the intrinsic activity of FeN4 sites was only tunable by varying thermal activation temperatures during the formation of FeN4 sites, which impacted the length of the Fe-N bonds and the local strains. The structural evolution of Fe-N bonds was examined at the atomic level. First-principles calculations further elucidated the origin of intrinsic activity improvement associated with the optimal local strain of the Fe-N bond.