| 1. |
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| 2. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
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| 4. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Gao, Xindi, et al.
(author)
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Cryptococcal Hsf3 controls intramitochondrial ROS homeostasis by regulating the respiratory process
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Mitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response. CnHsf3 acts in nuclei and mitochondria, and nuclear- and mitochondrial-targeting signals are required for its organelle-specific functions. It represses the expression of genes involved in the tricarboxylic acid cycle while promoting expression of genes involved in electron transfer chain. In addition, CnHsf3 responds to multiple intramitochondrial stresses; this response is mediated by oxidation of the cysteine residue on its DNA binding domain, which enhances DNA binding. Our results reveal a function of HSF proteins in regulating mtROS homeostasis that is independent of the unfolded protein response.
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| 6. |
- Hyde, K. D., et al.
(author)
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Global consortium for the classification of fungi and fungus-like taxa
- 2023
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In: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Journal article (peer-reviewed)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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| 7. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 8. |
- Na, Meng, et al.
(author)
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Higher stand densities can promote soil carbon storage after conversion of temperate mixed natural forests to larch plantations
- 2021
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In: European Journal of Forest Research. - : Springer Science and Business Media LLC. - 1612-4669 .- 1612-4677. ; 140:2, s. 373-386
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Journal article (peer-reviewed)abstract
- Soil carbon (C) reservoirs held in forests play a significant role in the global C cycle. However, harvesting natural forests tend to lead to soil C loss, which can be countered by the establishment of plantations after clear cutting. Therefore, there is a need to determine how forest management can affect soil C sequestration. The management of stand density could provide an effective tool to control soil C sequestration, yet how stand density influences soil C remains an open question. To address this question, we investigated soil C storage in 8-year pure hybrid larch (Larix spp.) plantations with three densities (2000 trees ha−1, 3300 trees ha−1 and 4400 trees ha−1), established following the harvesting of secondary mixed natural forest. We found that soil C storage increased with higher tree density, which mainly correlated with increases of dissolved organic C as well as litter and root C input. In addition, soil respiration decreased with higher tree density during the most productive periods of warm and moist conditions. The reduced SOM decomposition suggested by lowered respiration was also corroborated with reduced levels of plant litter decomposition. The stimulated inputs and reduced exports of C from the forest floor resulted in a 40% higher soil C stock in high- compared to low-density forests within 8 years after plantation, providing effective advice for forest management to promote soil C sequestration in ecosystems.
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| 9. |
- Pathak, Surajit, et al.
(author)
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Association of MicroRNA-652 Expression with Radiation Response of Colorectal Cancer : A Study from Rectal Cancer Patients in a Swedish Trial of Preoperative Radiotherapy
- 2023
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In: Current Gene Therapy. - : Bentham Science Publishers. - 1566-5232 .- 1875-5631. ; 23:5, s. 356-367
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Journal article (peer-reviewed)abstract
- Background: Radiotherapy is a standard adjuvant therapy in patients with progressive rectal cancer, but many patients are resistant to radiotherapy, leading to poor prognosis. Our study identified microRNA-652 (miR-652) value on radiotherapy response and outcome in rectal cancer patients.Methods: miR-652 expression was determined by qPCR in primary rectal cancer from 48 patients with and 53 patients without radiotherapy. The association of miR-652 with biological factors and the prognosis was examined. The biological function of miR-652 was identified through TCGA and GEPIA database searches. Two human colon cancer cell lines (HCT116 p53(+/+) and p53(-/-)) were used for in vitro study. The molecular interactions of miR-652 and tumor suppressor genes were studied through a computational approach.Results: In RT patients, miR-652 expression was significantly decreased in cancers when compared to non-radiotherapy cases (P = 0.002). High miR-652 expression in non-RT patients was with increased apoptosis marker (P = 0.036), ATM (P = 0.010), and DNp73 expression (P = 0.009). High miR-652 expression was related to worse disease-free survival of non-radiotherapy patients, independent of gender, age, tumor stage, and differentiation (P = 0.028; HR = 7.398, 95% CI 0.217-3.786). The biological functional analysis further identified the prognostic value and potential relationship of miR-652 with apoptosis in rectal cancer. miR-652 expression in cancers was negatively related to WRAP53 expression (P = 0.022). After miR-652 inhibition, the estimation of reactive oxygen species, caspase activity, and apoptosis in HCT116 p53(+/+ )cells was significantly increased compared with HCT116 p53(-/-) cells after radiation. The results of the molecular docking analysis show that the miR652-CTNNBL1 and miR652-TP53 were highly stable.Conclusion: Our findings suggest the potential value of miR-652 expression as a marker for the prediction of radiation response and clinical outcome in rectal cancer patients.
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| 10. |
- Sun, Y., et al.
(author)
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Battery degradation evaluation based on impedance spectra using a limited number of voltage-capacity curves
- 2024
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In: eTransporation. - : Elsevier. - 2590-1168. ; 22
-
Journal article (peer-reviewed)abstract
- Degradation prediction is crucial for ensuring safe and reliable operation of batteries. However, relying solely on capacity to characterize aging cannot comprehensively represent the health status of the battery. This work explores the potential of using a limited number of partial voltage-capacity curves to evaluate battery degradation with the aid of deep learning approaches, which can be used for onboard applications. A sequence-to-sequence model is proposed to predict the electrochemical impedance spectra during battery degradation. It only uses capacity sequences within a specific voltage range at fixed voltage increments from a limited number of cycles, which can be flexibly adapted to different life stages in an end-to-end manner. The proposed method has been validated based on the developed degradation dataset. The root mean square errors for the prediction of impedance spectra are less than 1.48 mΩ. Capacities and resistances associated with electrochemical processes can be further extracted from the obtained impedance spectra, facilitating a comprehensive evaluation of battery degradation. As a limited number of measured data are needed, the proposed method can reduce data storage requirements and computational demands, which enables fast and comprehensive aging diagnosis.
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| 11. |
- Wang, Ning, et al.
(author)
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Boride-derived oxygen-evolution catalysts
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12
-
Journal article (peer-reviewed)abstract
- Metal borides/borates have been considered promising as oxygen evolution reaction catalysts; however, to date, there is a dearth of evidence of long-term stability at practical current densities. Here we report a phase composition modulation approach to fabricate effective borides/borates-based catalysts. We find that metal borides in-situ formed metal borates are responsible for their high activity. This knowledge prompts us to synthesize NiFe-Boride, and to use it as a templating precursor to form an active NiFe-Borate catalyst. This boride-derived oxide catalyzes oxygen evolution with an overpotential of 167 mV at 10 mA/cm2 in 1 M KOH electrolyte and requires a record-low overpotential of 460 mV to maintain water splitting performance for over 400 h at current density of 1 A/cm2. We couple the catalyst with CO reduction in an alkaline membrane electrode assembly electrolyser, reporting stable C2H4 electrosynthesis at current density 200 mA/cm2 for over 80 h.
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| 12. |
- Xie, Sisi, et al.
(author)
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Dietary ketone body-escalated histone acetylation in megakaryocytes alleviates chemotherapy-induced thrombocytopenia
- 2022
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In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 14:673
-
Journal article (peer-reviewed)abstract
- Chemotherapy-induced thrombocytopenia (CIT) is a severe complication in patients with cancer that can lead to impaired therapeutic outcome and survival. Clinically, therapeutic options for CIT are limited by severe adverse effects and high economic burdens. Here, we demonstrate that ketogenic diets alleviate CIT in both animals and humans without causing thrombocytosis. Mechanistically, ketogenic diet-induced circulating beta-hydroxybutyrate (beta-OHB) increased histone H3 acetylation in bone marrow megakaryocytes. Gain- and loss-of-function experiments revealed a distinct role of 3-beta-hydroxybutyrate dehydrogenase (BDH)-mediated ketone body metabolism in promoting histone acetylation, which promoted the transcription of platelet biogenesis genes and induced thrombocytopoiesis. Genetic depletion of the megakaryocyte-specific ketone body transporter monocarboxylate transporter 1 (MCT1) or pharmacological targeting of MCT1 blocked beta-OHB-induced thrombocytopoiesis in mice. A ketogenesis-promoting diet alleviated CIT in mouse models. Moreover, a ketogenic diet modestly increased platelet counts without causing thrombocytosis in healthy volunteers, and a ketogenic lifestyle inversely correlated with CIT in patients with cancer. Together, we provide mechanistic insights into a ketone body-MCT1-BDH-histone acetylation-platelet biogenesis axis in megakaryocytes and propose a non-toxic, low-cost dietary intervention for combating CIT.
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| 13. |
- Zhao, Meng, et al.
(author)
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Three-dimensional cross-linked sugarcane bagasse carbon material: A substitute for graphene with excellent performance in capacitive deionization and highly efficient Cu2+removal
- 2024
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In: Colloids and Surfaces A. - : ELSEVIER. - 0927-7757 .- 1873-4359. ; 684
-
Journal article (peer-reviewed)abstract
- Capacitive deionization (CDI) is a high-performance, low-energy consumption, and environmentally friendly water treatment technology with a broad application prospect in heavy metal removal. Selecting electrode materials with high capacitance and low resistance is essential for improving CDI's desalting efficiency. This article discusses the utilization of sugarcane bagasse (C-N-X) and the production procedures of CDI materials. The unique 3D cross-linked structure of C-N-X provides excellent mass transfer properties and significant advantages in capacitance and conductivity. The results of X-ray photoelectron spectroscopy (XPS) and Fourier Transform Infrared Spectrometer (FTIR) show that bagasse biochar with graphene-like structure and abundant functional groups provides active sites for Cu2+ removal. In this paper, C-N-X is first used as CDI electrode material to remove Cu2+. Electrochemical tests show that the specific capacitance of C-N-X is still stable at about 47 F g ? 1, and the removal capacity of Cu2+ (25 mg L-1) reaches 66.79 mg g-1 within 4 h after 700 cycles. The experimental results and DFT calculations confirm the adsorption selectivity of C -N-700 for Cu2+.
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| 14. |
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| 15. |
- Bu, Xiangning, et al.
(author)
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Exploring the Relationships between Gas Dispersion Parameters and Differential Pressure Fluctuations in a Column Flotation
- 2021
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In: ACS Omega. - : Elsevier. - 2470-1343. ; 6:34, s. 21900-21908
-
Journal article (peer-reviewed)abstract
- Flotation separation, which is the most important mineral beneficiation technique, is dependent on gas dispersion (hydrodynamic conditions). Thus, many investigations have focused on the precise determination of hydrodynamic conditions such as Reynolds number of the bubbles, bubble velocity, and bubble diameter. However, few studies have examined their relationships with pressure fluctuations in a column flotation. This study introduced the differential pressure fluctuations as an actual variable that could be considered to determine the collection zone’s hydrodynamic conditions in a cyclonic microbubble flotation column. In general, the outcomes indicated that superficial gas velocity had the most substantial relationship with the differential pressure fluctuations among other flotation factors (such as pump speed, superficial gas velocity, superficial water velocity, and frother dosage). Furthermore, a high coefficient of determination (R2 > 0.77) for the equation generated to assess the relationships demonstrated that differential pressure fluctuations could be used as a promising tool to determine the hydrodynamic parameters’ characteristics in the flotation columns.
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| 16. |
- Byun, Jinyoung, et al.
(author)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
-
In: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
-
Journal article (peer-reviewed)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 17. |
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| 18. |
- Erickson, Brittany A., et al.
(author)
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Incorporating Full Elastodynamic Effects and Dipping Fault Geometries in Community Code Verification Exercises for Simulations of Earthquake Sequences and Aseismic Slip (SEAS)
- 2023
-
In: Bulletin of The Seismological Society of America (BSSA). - : SEISMOLOGICAL SOC AMER. - 0037-1106 .- 1943-3573. ; 113:2, s. 499-523
-
Journal article (peer-reviewed)abstract
- Numerical modeling of earthquake dynamics and derived insight for seismic hazard relies on credible, reproducible model results. The sequences of earthquakes and aseismic slip (SEAS) initiative has set out to facilitate community code comparisons, and verify and advance the next generation of physics-based earthquake models that reproduce all phases of the seis-mic cycle. With the goal of advancing SEAS models to robustly incorporate physical and geo-metrical complexities, here we present code comparison results from two new benchmark problems: BP1-FD considers full elastodynamic effects, and BP3-QD considers dipping fault geometries. Seven and eight modeling groups participated in BP1-FD and BP3-QD, respectively, allowing us to explore these physical ingredients across multiple codes and better understand associated numerical considerations. With new comparison metrics, we find that numerical resolution and computational domain size are critical parameters to obtain matching results. Codes for BP1-FD implement different criteria for switching between quasi-static and dynamic solvers, which require tuning to obtain matching results. In BP3-QD, proper remote boundary conditions consistent with specified rigid body translation are required to obtain matching surface displacements. With these numerical and mathematical issues resolved, we obtain excellent quantitative agreements among codes in earthquake interevent times, event moments, and coseismic slip, with reasonable agreements made in peak slip rates and rupture arrival time. We find that including full inertial effects generates events with larger slip rates and rupture speeds compared to the quasi-dynamic counterpart. For BP3-QD, both dip angle and sense of motion (thrust versus normal faulting) alter ground motion on the hanging and foot walls, and influence event patterns, with some sequences exhibiting similar-size character-istic earthquakes, and others exhibiting different-size events. These findings underscore the importance of considering full elastodynamics and nonvertical dip angles in SEAS models, as both influence short-and long-term earthquake behavior and are relevant to seismic hazard.
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| 19. |
- Fan, Lizhou, et al.
(author)
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Molecular Functionalization of NiO Nanocatalyst for Enhanced Water Oxidation by Electronic Structure Engineering
- 2020
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In: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 13:22, s. 5901-5909
-
Journal article (peer-reviewed)abstract
- Tuning the local environment of nanomaterial-based catalysts has emerged as an effective approach to optimize their oxygen evolution reaction (OER) performance, yet the controlled electronic modulation around surface active sites remains a great challenge. Herein, directed electronic modulation of NiO nanoparticles was achieved by simple surface molecular modification with small organic molecules. By adjusting the electronic properties of modifying molecules, the local electronic structure was rationally tailored and a close electronic structure-activity relationship was discovered: the increasing electron-withdrawing modification readily decreased the electron density around surface Ni sites, accelerating the reaction kinetics and improving OER activity, and vice versa. Detailed investigation by operando Raman spectroelectrochemistry revealed that the electron-withdrawing modification facilitates the charge-transfer kinetics, stimulates the catalyst reconstruction, and promotes abundant high-valent gamma-NiOOH reactive species generation. The NiO-C(6)F(5)catalyst, with the optimized electronic environment, exhibited superior performance towards water oxidation. This work provides a well-designed and effective approach for heterogeneous catalyst fabrication under the molecular level.
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| 20. |
- Fan, Lizhou, et al.
(author)
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Promoting the Fe(VI) active species generation by structural and electronic modulation of efficient iron oxide based water oxidation catalyst without Ni or Co
- 2020
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In: Nano Energy. - : Elsevier BV. - 2211-2855 .- 2211-3282. ; 72
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Journal article (peer-reviewed)abstract
- Fe is considered as a promising alternative for OER catalysts owing to its high natural abundance and low cost. Due to the low conductivity and sluggish catalytic kinetics, the catalytic efficiency of Fe-rich catalysts is far from less abundant Ni, Co-rich alternatives and has been hardly improved without the involvement of Ni or Co. The lower activity of Fe-rich catalysts renders the real active center of state-of-the-art NiFe, CoFe catalyst in long-term scientific debate, despite of detection of Fe-based active intermediates in these catalysts during catalytic process. In the present work, we fabricated a series of sub-5 nm Fe1-yCryOx nanocatalysts via a simple solvothermal method, achieving systematically promoted high-valent Fe(VI) species generation by structural and electronic modulation, displaying highly active OER performance without involvement of Ni or Co. Detailed investigation revealed that the high OER activity is related to the ultrasmall nanoparticle size that promotes abundant edge- and corner-site exposure at catalyst surface, which involves in OER as highly reactive site; and the incorporated Cr ions that remarkably accelerate the charge transfer kinetics, providing an effective conduit as well as suitable host for high-valent active intermediate. This work reveals the structural prerequisites for efficient Fe-rich OER catalyst fabrication, inspiring deeper understanding of the structure-activity relationship as well as OER mechanism of Fe-based catalysts.
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| 21. |
- Fan, Yue, et al.
(author)
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Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
- 2024
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In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:7, s. 926-944
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.
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| 22. |
- Fu, Xi, et al.
(author)
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Associations between environmental characteristics, high-resolution indoor microbiome, metabolome and allergic and non-allergic rhinitis symptoms for junior high school students
- 2023
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In: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 25:4, s. 791-804
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Journal article (peer-reviewed)abstract
- Rhinitis is one of the most prevalent chronic diseases globally. Microbiome exposure affects the occurrence of rhinitis. However, previous studies did not differentiate allergic rhinitis (AR) and non-allergic rhinitis (NAR) in the microbial association analysis. In this study, we investigate 347 students in 8 junior high schools, Terengganu, Malaysia, who were categorized as healthy (70.9%), AR (13.8%) and NAR (15.3%) based on a self-administered questionnaire and skin prick tests of pollen, pet, mould and house dust mite allergens. Classroom microbial and metabolite exposure in vacuumed dust was characterized by PacBio long-read amplicon sequencing, quantitative PCR and LC-MS-based untargeted metabolomics. Our findings indicate a similar microbial association pattern between AR and NAR. The richness in Gammaproteobacteria was negatively associated with AR and NAR symptoms, whereas total fungal richness was positively associated with AR and NAR symptoms (p < 0.05). Brasilonema bromeliae and Aeromonas enteropelogenes were negatively associated with AR and NAR, and Deinococcus was positively associated with AR and NAR (p < 0.01). Pipecolic acid was protectively associated with AR and NAR symptoms (OR = 0.06 and 0.13, p = 0.009 and 0.045). A neural network analysis showed that B. bromeliae was co-occurring with pipecolic acid, suggesting that the protective role of this species may be mediated by releasing pipecolic acid. Indoor relative humidity and the weight of vacuum dust were associated with AR and NAR, respectively (p < 0.05), but the health effects were mediated by two protective bacterial species, Aliinostoc morphoplasticum and Ilumatobacter fluminis. Overall, our study reported a similar microbial association pattern between AR and NAR and also revealed the complex interactions between microbial species, environmental characteristics, and rhinitis symptoms.
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| 23. |
- Fu, Xi, et al.
(author)
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Associations between respiratory infections and bacterial microbiome in student dormitories in Northern China.
- 2020
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In: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 30:5, s. 816-826
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Journal article (peer-reviewed)abstract
- Recent studies reveal that the microbial diversity and composition in the respiratory tract are related to the susceptibility, development, and progression of respiratory infections. Indoor microorganisms can transmit into the respiratory tract through breathing, but their role in infections is unclear. Here, we present the first association study between the indoor microbiome and respiratory infections. In total, 357 students living in 86 dormitory rooms in Shanxi University were randomly selected to survey symptoms of infections. Settled air dust was collected to characterize bacterial compositions by 16S rRNA sequencing. The overall microbial richness was not associated with respiratory infections, but microorganisms from specific phylogenetic classes showed various associations. Taxa richness and abundance of Actinobacteria were protectively associated with infections (P < .05). The abundance of several genera in Gammaproteobacteria, including Haemophilus, Klebsiella, Buttiauxella, and Raoultella, was positively associated with infections (P < .005). The role of these microorganisms was consistent with previous human microbiota studies. Building age was associated with the overall microbial composition variation in dormitories and negatively associated with three potential risk genera in Proteobacteria (P < .05). The weight of vacuum dust was positively associated with a protective genus, Micrococcus in Actinobacteria (P < .05).
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| 24. |
- Fu, Xi, et al.
(author)
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Associations between species-level indoor microbiome, environmental characteristics, and asthma in junior high schools of Terengganu, Malaysia
- 2022
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In: Air quality, atmosphere and health. - : Springer Nature. - 1873-9318 .- 1873-9326. ; 15:6, s. 1043-1055
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Journal article (peer-reviewed)abstract
- Indoor microbiome exposure is important for asthma development, but current studies characterize the microbiome at the genus or above levels due to technical limitations. We aim to profile bacterial and fungal composition and concentration at the species level and assess its potential health effects. Four hundred sixty-three students from 8 junior high schools in Terengganu, Malaysia, were surveyed for asthma symptoms. Full-length PacBio amplicon sequencing and qPCR were conducted to quantify the absolute microbial concentration in the vacuum dust of the selected classroom. In total, 1358 bacterial and 358 fungal species were characterized, and drastic compositional variation was observed among classrooms. Three-level linear regression analyses revealed that taxa richness in Cyanobacteria were negatively associated with asthma (FDR < 0.001). The absolute concentration of Nocardioides exalbidus was protectively associated with asthma, and four bacteria species were positively associated with asthma (FDR < 0.1). Interestingly, all five species were recently isolated and characterized in Asian countries and never reported to associate with asthma. Indoor NO2 and formaldehyde concentration were associated with the overall bacterial community variation and fungal richness, respectively (p < 0.05). No environmental characteristics were directly associated with asthma, but indoor relative humidity, CO2 concentration, and weight of vacuum dust were associated with the asthma-related species (p < 0.05), suggesting a potential indirect health effect on students. This is the first study to characterize indoor microbiome and asthma-associated microorganisms at the species level, representing a region-specific microbiome exposure pattern in a tropical Asian country.
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| 25. |
- Fu, Xi, et al.
(author)
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Associations between the indoor microbiome, environmental characteristics and respiratory infections in junior high school students of Johor Bahru, Malaysia.
- 2021
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In: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 23:8, s. 1171-1181
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Journal article (peer-reviewed)abstract
- Pathogens are commonly present in the human respiratory tract, but symptoms are varied among individuals. The interactions between pathogens, commensal microorganisms and host immune systems are important in shaping the susceptibility, development and severity of respiratory diseases. Compared to the extensive studies on the human microbiota, few studies reported the association between indoor microbiome exposure and respiratory infections. In this study, 308 students from 21 classrooms were randomly selected to survey the occurrence of respiratory infections in junior high schools of Johor Bahru, Malaysia. Vacuum dust was collected from the floor, chairs and desks of these classrooms, and high-throughput amplicon sequencing (16S rRNA and ITS) and quantitative PCR were conducted to characterize the absolute concentration of the indoor microorganisms. Fifteen bacterial genera in the classes Actinobacteria, Alphaproteobacteria, and Cyanobacteria were protectively associated with respiratory infections (p < 0.01), and these bacteria were mainly derived from the outdoor environment. Previous studies also reported that outdoor environmental bacteria were protectively associated with chronic respiratory diseases, such as asthma, but the genera identified were different between acute and chronic respiratory diseases. Four fungal genera from Ascomycota, including Devriesia, Endocarpon, Sarcinomyces and an unclassified genus from Herpotrichillaceae, were protectively associated with respiratory infections (p < 0.01). House dust mite (HDM) allergens and outdoor NO2 concentration were associated with respiratory infections and infection-related microorganisms. A causal mediation analysis revealed that the health effects of HDM and NO2 were partially or fully mediated by the indoor microorganisms. This is the first study to explore the association between environmental characteristics, microbiome exposure and respiratory infections in a public indoor environment, expanding our understanding of the complex interactions among these factors.
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