| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Guo, Hui-Hui, et al.
(författare)
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Alleviation of allergic asthma by rosmarinic acid via gut-lung axis
- 2024
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Ingår i: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. Purpose: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. Methods: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. Results: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NF kappa B mediated pulmonary inflammation and oxidative stress. Conclusions: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiotaderived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
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| 4. |
- Chiu, Pei-Fang, et al.
(författare)
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Design, structure–activity relationships, and enzyme kinetic studies of tricyclic and tetracyclic coumarin–based sulfamates as steroid sulfatase inhibitors
- 2023
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Ingår i: Bioorganic chemistry. - : Elsevier BV. - 0045-2068. ; 138, s. 106581-106581
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with KI of 0.05 and 0.4 nM, and kinact/KI ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively.
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| 5. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 6. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 7. |
- Qin, Shuang-Jian, et al.
(författare)
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Neurotoxicity of fine and ultrafine particulate matter : a comprehensive review using a toxicity pathway-oriented adverse outcome pathway framework
- 2024
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 947
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Forskningsöversikt (refereegranskat)abstract
- Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.
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| 8. |
- Wang, Fang, et al.
(författare)
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Emerging contaminants: A One Health perspective
- 2024
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Ingår i: Innovation. - 2666-6758. ; 5
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Forskningsöversikt (refereegranskat)abstract
- Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both people and the planet. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the ongoing efforts to establish the UN's Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.
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| 9. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 10. |
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| 11. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
- Berger, Ashton C, et al.
(författare)
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A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:4, s. 690-705.e9
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
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| 14. |
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| 15. |
- Chen, Baoqing, et al.
(författare)
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The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 159:6, s. 2146-2162
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Tidskriftsartikel (refereegranskat)abstract
- Background & AimsChromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer–associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.MethodsWe performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls). CRC cells were also analyzed by immunofluorescence microscopy, γ-H2AX, and senescence assays. CCAT2 transgene and control mice were given azoxymethane and dextran sulfate sodium to induce colon tumors. We performed gene expression array and mass spectrometry to detect downstream targets of CCAT2 lncRNA. We characterized interactions between CCAT2 with downstream proteins using MS2 pull-down, RNA immunoprecipitation, and selective 2′-hydroxyl acylation analyzed by primer extension analyses. Downstream proteins were overexpressed in CRC cells and analyzed for CIN. Gene expression levels were measured in CRC and non-tumor tissues from 5 cohorts, comprising more than 900 patients.ResultsHigh expression of CCAT2 induced CIN in CRC cell lines and increased resistance to 5-fluorouracil and oxaliplatin. Mice that expressed the CCAT2 transgene developed chromosome abnormalities, and colon organoids derived from crypt cells of these mice had a higher percentage of chromosome abnormalities compared with organoids from control mice. The transgenic mice given azoxymethane and dextran sulfate sodium developed more and larger colon polyps than control mice given these agents. Microarray analysis and mass spectrometry indicated that expression of CCAT2 increased expression of genes involved in ribosome biogenesis and protein synthesis. CCAT2 lncRNA interacted directly with and stabilized BOP1 ribosomal biogenesis factor (BOP1). CCAT2 also increased expression of MYC, which activated expression of BOP1. Overexpression of BOP1 in CRC cell lines resulted in chromosomal missegregation errors, and increased colony formation, and invasiveness, whereas BOP1 knockdown reduced viability. BOP1 promoted CIN by increasing the active form of aurora kinase B, which regulates chromosomal segregation. BOP1 was overexpressed in polyp tissues from CCAT2 transgenic mice compared with healthy tissue. CCAT2 lncRNA and BOP1 mRNA or protein were all increased in microsatellite stable tumors (characterized by CIN), but not in tumors with microsatellite instability compared with nontumor tissues. Increased levels of CCAT2 lncRNA and BOP1 mRNA correlated with each other and with shorter survival times of patients.ConclusionsWe found that overexpression of CCAT2 in colon cells promotes CIN and carcinogenesis by stabilizing and inducing expression of BOP1 an activator of aurora kinase B. Strategies to target this pathway might be developed for treatment of patients with microsatellite stable colorectal tumors.
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| 16. |
- Chen, Chao, et al.
(författare)
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Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
- 2020
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10642-10662
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
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| 17. |
- Chen, Hui, et al.
(författare)
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Associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay diet with brain structural markers and their changes
- 2024
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Ingår i: Alzheimer's & Dementia. - 1552-5260 .- 1552-5279. ; 20:2, s. 1190-1200
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The associations of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with brain structural changes are unclear.METHODS: Among 26,466 UK Biobank participants, a 15-point MIND score was calculated from 24-hour diet recalls from 2009 to 2012. We assessed its associations with 17 magnetic-resonance-derived brain volumetric markers and their longitudinal changes and explored whether genetic factors modify the associations.RESULTS: Higher MIND adherence was associated with larger volumes of thalamus, putamen, pallidum, hippocampus, and accumbens (beta per 3-unit increment ranging from 0.024 to 0.033) and lower white matter hyperintensities (P-trends < 0.05), regardless of genetic predispositions of Alzheimer's disease. MIND score was not associated with their longitudinal changes (P > 0.05) over a median of 2.2 years among participants with repeated imaging assessments (N = 2963), but was associated with slower atrophy in putamen (beta: 0.026, P-trend = 0.044) and pallidum (beta: 0.030, P-trend = 0.033) among APOE ε4 non-carriers (N = 654).DISCUSSION: The MIND diet showed beneficial associations with certain brain imaging markers, and its associations with long-term brain structural changes warrants future investigation.
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| 18. |
- Dong, Yaa-Hui, et al.
(författare)
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Use of Inhaled Corticosteroids in Patients With COPD and the Risk of TB and Influenza A Systematic Review and Meta-analysis of Randomized Controlled Trials
- 2014
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Ingår i: Chest. - : Elsevier BV. - 1931-3543 .- 0012-3692. ; 145:6, s. 1286-1297
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However the risks of other respiratory infections such as TB and influenza remain unclear. Methods: Through a comprehensive literature search of MEDLINE EMBASE CINAHL Cochrane Library and ClinicalTrials.gov from inception to July 2013 we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto Mantel-Haenszel and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza. Results: Twenty-five trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment ICS treatment was associated with a significantly higher risk of TB (Peto OR 2.29 95% CI 1.04-5.03) but not influenza (Peto OR 1.24 95% CI 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667 respectively). Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD which deserve further investigation.
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| 19. |
- Ji, Xinyu, et al.
(författare)
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Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients
- 2020
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 14:11, s. 2759-2774
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Tidskriftsartikel (refereegranskat)abstract
- Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non-small-cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early-stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30–2.09, P = 4.52 × 10−5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87–1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407TRIM27 methylation in NSCLC. LUSC patients had a higher average pack-year of smoking (37.49LUAD vs 54.79LUSC, P = 1.03 × 10−19) and included a higher proportion of current smokers than LUAD patients (28.24%LUAD vs 34.09%LUSC, P = 0.037). cg05293407TRIM27 was significantly associated with overall survival only in NSCLC patients with medium–high pack-year of smoking (HR = 1.58, 95% CI: 1.26–1.96, P = 5.25 × 10−5). We conclude that cg05293407TRIM27 methylation is a potential predictor of LUSC prognosis, and smoking intensity may impact on its prognostic value across the various types of NSCLC.
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| 20. |
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| 21. |
- Jiang, Qing-Hui, et al.
(författare)
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Ferroic properties of highly dense multiferroic Bi1-xLa0.05TbxFeO3 ceramics via sheltered spark plasma sintering
- 2008
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Ingår i: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 91:7, s. 2189-2194
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Tidskriftsartikel (refereegranskat)abstract
- Multiferroic Bi0.95-xLa0.05TbxFeO3 (BLTFO) ceramics were prepared by spark plasma sintering. The protection of CeO2 powders in the spark plasma sintering process can effectively restrain the valence fluctuation of iron ions and high-dense BLTFO ceramics with good dielectric and ferroelectric properties are fabricated. The BLTFO ceramics have low loss (tan delta similar to 5%) between 10(2) and 10(6) Hz. The doping of Tb can increase the dielectric and ferromagnetic properties, but decrease the ferroelectricity of BLTFO ceramics.
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| 22. |
- Kim, Ji Hoon, et al.
(författare)
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THE AGORA HIGH-RESOLUTION GALAXY SIMULATIONS COMPARISON PROJECT. II. ISOLATED DISK TEST
- 2016
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 833:2
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Tidskriftsartikel (refereegranskat)abstract
- Using an isolated Milky Way-mass galaxy simulation, we compare results from nine state-of-the-art gravito-hydrodynamics codes widely used in the numerical community. We utilize the infrastructure we have built for the AGORA High-resolution Galaxy Simulations Comparison Project. This includes the common disk initial conditions, common physics models (e.g., radiative cooling and UV background by the standardized package Grackle) and common analysis toolkit yt, all of which are publicly available. Subgrid physics models such as Jeans pressure floor, star formation, supernova feedback energy, and metal production are carefully constrained across code platforms. With numerical accuracy that resolves the disk scale height, we find that the codes overall agree well with one another in many dimensions including: gas and stellar surface densities, rotation curves, velocity dispersions, density and temperature distribution functions, disk vertical heights, stellar clumps, star formation rates, and Kennicutt-Schmidt relations. Quantities such as velocity dispersions are very robust (agreement within a few tens of percent at all radii) while measures like newly formed stellar clump mass functions show more significant variation (difference by up to a factor of ∼3). Systematic differences exist, for example, between mesh-based and particle-based codes in the low-density region, and between more diffusive and less diffusive schemes in the high-density tail of the density distribution. Yet intrinsic code differences are generally small compared to the variations in numerical implementations of the common subgrid physics such as supernova feedback. Our experiment reassures that, if adequately designed in accordance with our proposed common parameters, results of a modern high-resolution galaxy formation simulation are more sensitive to input physics than to intrinsic differences in numerical schemes.
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| 23. |
- Kozhevnikov, Evgeny, et al.
(författare)
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A dual-transduction-integrated biosensing system to examine the 3D cell-culture for bone regeneration
- 2019
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Ingår i: Biosensors & bioelectronics. - : ELSEVIER ADVANCED TECHNOLOGY. - 0956-5663 .- 1873-4235. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional (3D) cell cultures developed with living cells and scaffolds have demonstrated outstanding potential for tissue engineering and regenerative medicine applications. However, no suitable tools are available to monitor dynamically variable cell behavior in such a complex microenvironment. In particular, simultaneously assessing cell behavior, cell secretion, and the general state of a 3D culture system is of a really challenging task. This paper presents our development of a dual-transduction-integrated biosensing system that assesses electrical impedance in conjunction with imaging techniques to simultaneously investigate the 3D cell-culture for bone regeneration. First, we created models to mimic the dynamic deposition of the extracellular matrix (ECM) in 3D culture, which underwent osteogenesis by incorporating different amounts of bone-ECM components (collagen, hydroxyapatite [HAp], and hyaluronic acid [HA]) into alginate-based hydrogels. The formed models were investigated by means of electrical impedance spectroscopy (EIS), with the results showing that the impedances increased linearly with collagen and hyaluronan, but changed in a more complex manner with HAp. Thereafter, we created two models that consisted of primary osteoblast cells (OBs), which expressed the enhanced green fluorescent protein (EGFP), and 4T1 cells, which secreted the EGFP-HA, in the alginate hydrogel. We found the capacitance (associated with impedance and measured by EIS) increased with the increases in initial embedded OBs, and also confirmed the cell proliferation over 3 days with the EGFP signal as monitored by the fluorescent imaging component in our system. Interestingly, the change in capacitance is found to be associated with OB migration following stimulation. Also, we show higher capacitance in 4T1 cells that secret HA when compared to control 4T1 cells after a 3-day culture. Taken together, we demonstrate that our biosensing system is able to investigate the dynamic process of 3D culture in a non-invasive and real-time manner.
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| 24. |
- Krueger, Jacob, et al.
(författare)
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Where is my feature and what is it about? A case study on recovering feature facets
- 2019
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Ingår i: Journal of Systems and Software. - : Elsevier BV. - 0164-1212. ; 152, s. 239-253
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Tidskriftsartikel (refereegranskat)abstract
- Developers commonly use features to define, manage, and communicate functionalities of a system. Unfortunately, the locations of features in code and other characteristics (feature facets), relevant for evolution and maintenance, are often poorly documented. Since developers change, and knowledge fades with time, such information often needs to be recovered. Modern projects boast a richness of information sources, such as pull requests, release logs, and otherwise specified domain knowledge. However, it is largely unknown from what sources the features, their locations, and their facets can be recovered. We present an exploratory study on identifying such information in two popular, variant-rich, and long-living systems: The 3D-printer firmware Marlin and the Android application Bitcoin-wallet. Besides the available information sources, we also investigated the projects' communities, communications, and development cultures. Our results show that a multitude of information sources (e.g., commit messages and pull requests) is helpful to recover features, locations, and facets to different extents. Pull requests were the most valuable source to recover facets, followed by commit messages and the issue tracker. As many of the studied information sources are, so far, rarely exploited in techniques for recovering features and their facets, we hope to inspire researchers and tool builders with our results. (C) 2019 Elsevier Inc. All rights reserved.
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| 25. |
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| 26. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 27. |
- Ling, Yiming, et al.
(författare)
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Observations of Kelvin-Helmholtz Waves in the Earth's Magnetotail Near the Lunar Orbit
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 123:5, s. 3836-3847
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Tidskriftsartikel (refereegranskat)abstract
- Kelvin‐Helmholtz waves (KHWs), which have been widely observed at the magnetopause in the region near the Earth, play an essential role in the transport of solar wind plasma and energy into the magnetosphere under dominantly northward interplanetary magnetic field (IMF) conditions. In this study, we present simultaneous observations of KHWs under the northward IMF observed by both the Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft in the Earth's magnetotail around the lunar orbit (at X ~ −50RE, Y ~ 30RE, dusk side) and the Geotail in the near‐Earth space (at X ~ −5RE, Y ~ −10RE, dawn side). The KHWs are quantitatively characterized by their dominant period, phase velocity, and wavelength, utilizing wavelet analysis and an approximation of their center‐of‐mass velocity. Our results suggest that the phase velocity and spatial scale of KHWs may increase as they propagate along the boundary layer toward the tail. Alternatively, the differences between the ARTEMIS and Geotail observations may indicate the possibility of dawn‐dusk asymmetry in the excited KHWs in this study. Our results strongly evidence the existence of the development of KHWs in terms of their wave frequency and scale size in the magnetotail and provide insight to the time evolution of KHWs along the magnetopause.
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| 28. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 29. |
- Mansouri, Kamel, et al.
(författare)
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CERAPP : Collaborative Estrogen Receptor Activity Prediction Project
- 2016
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:7, s. 1023-1033
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Humans are exposed to thousands of man-made chemicals in the environment. Some chemicals mimic natural endocrine hormones and, thus, have the potential to be endocrine disruptors. Most of these chemicals have never been tested for their ability to interact with the estrogen receptor (ER). Risk assessors need tools to prioritize chemicals for evaluation in costly in vivo tests, for instance, within the U.S. EPA Endocrine Disruptor Screening Program. OBJECTIVES: We describe a large-scale modeling project called CERAPP (Collaborative Estrogen Receptor Activity Prediction Project) and demonstrate the efficacy of using predictive computational models trained on high-throughput screening data to evaluate thousands of chemicals for ER-related activity and prioritize them for further testing. METHODS: CERAPP combined multiple models developed in collaboration with 17 groups in the United States and Europe to predict ER activity of a common set of 32,464 chemical structures. Quantitative structure-activity relationship models and docking approaches were employed, mostly using a common training set of 1,677 chemical structures provided by the U.S. EPA, to build a total of 40 categorical and 8 continuous models for binding, agonist, and antagonist ER activity. All predictions were evaluated on a set of 7,522 chemicals curated from the literature. To overcome the limitations of single models, a consensus was built by weighting models on scores based on their evaluated accuracies. RESULTS: Individual model scores ranged from 0.69 to 0.85, showing high prediction reliabilities. Out of the 32,464 chemicals, the consensus model predicted 4,001 chemicals (12.3%) as high priority actives and 6,742 potential actives (20.8%) to be considered for further testing.CONCLUSION: This project demonstrated the possibility to screen large libraries of chemicals using a consensus of different in silico approaches. This concept will be applied in future projects related to other end points.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Shen, Cheng, et al.
(författare)
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Increases of Offshore Wind Potential in a Warming World
- 2024
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Ingår i: Geophysical Research Letters. - 0094-8276.
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Tidskriftsartikel (refereegranskat)abstract
- Offshore wind farms, a rapidly expanding sector within wind energy, are playing a significant role in achieving global carbon neutrality, and this trend is to continue. Here, we utilize ERA5 reanalysis to correct offshore wind speed trends predicted by CMIP6 models. This approach led to enhanced projections for changes in offshore Wind Power Density (WPD) under four Shared Socioeconomic Pathways (SSPs) scenarios. Throughout the 21st century, global offshore WPD is projected to follow an upward trend across all SSP scenarios. Notably, Europe stands out with the most substantial increase in offshore WPD among regions with higher current installations, projected to reach up to 26% under 4°C global warming. Our study uncovers a notable increase of global offshore WPD in a warmer climate, which offers valuable insights for the strategic planning of future global wind energy.
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| 35. |
- Shiota, Takuya, et al.
(författare)
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Molecular architecture of the active mitochondrial protein gate
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6255, s. 1544-1548
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria fulfill central functions in cellular energetics, metabolism, and signaling. The outer membrane translocator complex (the TOM complex) imports most mitochondrial proteins, but its architecture is unknown. Using a cross-linking approach, we mapped the active translocator down to single amino acid residues, revealing different transport paths for preproteins through the Tom40 channel. An N-terminal segment of Tom40 passes from the cytosol through the channel to recruit chaperones fromthe intermembrane space that guide the transfer of hydrophobic preproteins. The translocator contains three Tom40 beta-barrel channels sandwiched between a central alpha-helical Tom22 receptor cluster and external regulatory Tom proteins. The preprotein-translocating trimeric complex exchanges with a dimeric isoform to assemble new TOM complexes. Dynamic coupling of alpha-helical receptors, beta-barrel channels, and chaperones generates a versatile machinery that transports about 1000 different proteins.
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| 36. |
- Sun, Yong-Hui, et al.
(författare)
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Gla-domain mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding.
- 2003
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 101:6, s. 2277-2284
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Tidskriftsartikel (refereegranskat)abstract
- Protein C is a member of the vitamin K-dependent protein family. Proteins in this family have similar gamma-carboxyglutamic acid (Gla)-rich domains, but their affinities for negatively charged phospholipid membranes vary more. than 1000-fold.. We have shown that it is possible to enhance anticoagulant activity and membrane affinity of protein C by selective mutagenesis of the Gla domain. In this study, 3,new mutants, Q10G11N12 (OGN), S23E32D33Y44 (SEDY), and Q10G11N12S23E32D33Y44 (QGNSEDY), were created. In plasma-based coagulation assays, the activated form of QGNSEDY (QGNSEDY-APC) demonstrated approximately 20-fold higher anticoagulant activity than wild-type activated protein C (WTAPC), while QGN-APC and SEDY-APC did not. Both normal activated factor V (FVa) and FVa Leiden (Arg506Gln) were degraded much more efficiently by QGNSEDY-APC than by WT APC. in the, presence as well as. in the absence of protein S. Binding of protein C variants. to negatively charged phospholipid membranes was investigated using light scattering and the BIAcore technique. QGNSEDY demonstrated 3- to 7-fold enhanced binding as, compared with WT protein C, suggesting, the membrane affinity to be influenced by several residues located at different parts of, the Gla domain. The anticoagulant activity as well as phospholipid binding ability was only enhanced when multiple regions of the Gla domain were modified. The results provide insights into the molecular mechanisms that are involved in determining the binding affinity of the interaction between Gla domains and phospolipid membranes. The unique properties of QGNSEDY-APC suggest this APC variant possibly to have greater therapeutic potential than WT APC.
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| 37. |
- Tian, Jian-jun, et al.
(författare)
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Influence of heat treatment on fracture and magnetic properties of radially oriented Sm 2 Co 17 permanent magnets
- 2007
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Ingår i: Transactions of Nonferrous Metals Society of China. - 1003-6326 .- 2210-3384. ; 17:3, s. 491-495
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Tidskriftsartikel (refereegranskat)abstract
- The quenching, fracture and aging treatment of radially oriented Sm2Co17 ring magnets were investigated. The results indicate that the ring magnets have obvious anisotropy of thermal expansion, which easily leads to the splits of the magnets during quenching. The fracture is brittle cleavage fracture. The difference (δa) of the expansion coefficient reaches the maximum value at 800–850 °C. So, various quenching processes at different steps are adopted in order to reduce the splits. When the magnets are aged. 1:5 phase precipitates from the 2:17 matrix phase and forms a cellular microstructure with 2:17 phase. BHmax and 3Hc reach the maximum value 226 kJ/m3 and 2170 kA/m after being aged at 850 °C for 4 h and 8 h, respectively. The aging treatment at 850 °C has little influence on remanence(Br), which can always keep a high value (≥1.0 T). Through appropriate heat treatment, the ring magnets have uniform cellular microstructure and excellent magnetic properties: Br1.0T, 3Hc≥2 100 kA/m, BHmax≥220 kJ/m3.
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| 38. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 39. |
- Wang, Mengmeng, et al.
(författare)
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Statistical analysis of whistler precursors upstream of foreshock transient shocks : MMS observations
- 2024
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Using the high-time-resolution data from the Magnetospheric Multiscale mission, precursor waves upstream of foreshock transient (FT) shocks are statistically investigated using the four-spacecraft timing method. The wave frequencies and wave vectors determined in the plasma rest frame (PRF) are shown to follow the cold plasma dispersion relation for whistler waves. Combining with the feature of the right-hand polarization in the PRF, the precursors are identified as whistler-mode waves around the lower hybrid frequency. The occurrence of whistler precursors is independent of the Alfvén Mach number and the FT shock normal angle. More importantly, all the whistler precursors have group velocities pointing upstream in the shock frame, suggesting the dispersive radiation to be a possible generation mechanism. The study improves the understanding of not only the whistler precursors but also the overall FT shock dynamics.
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| 40. |
- Wang, Yi-Qiang, et al.
(författare)
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Analysis of expressed sequence tags from Ginkgo mature foliage in China
- 2010
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Ingår i: TREE GENET GENOMES. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 6:3, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- Ginkgo biloba L. is a tree native to China, which has large importance within medicine and horticulture. The extracts from Ginkgo mature leaves with rich flavonoids and terpenoids are commonly used for a variety of folk remedies. We constructed a cDNA library derived from mature leaves of Ginkgo, which consisted of 8.12 x 10(5) clones with the insert length of 500-2,000 bp. We performed an analysis of expressed sequence tags (ESTs) and obtained partial sequences from 2,039 clones, which represented 1,437 unigenes consisting of 249 contigs and 1,188 singletons. The 2,039 ESTs were submitted to GenBank (dbEST) at NCBI and were assigned GenBank accession numbers from GE647881 to GE649919. The 1,235 cDNA clones out of 2,039 (60.1%) were assigned putative functions, and the remaining 804 clones were not similar to any known gene sequences in the databases. The five largest categories of Ginkgo clones were: "energy" (19.4%), "disease/defense" (16%), "metabolism" (11.3%), "unclassified proteins" (12.5%), and "secondary metabolism" (9%). The highly expressed transcripts in the cDNA library were some genes related to photosynthesis, disease/defense, and flavonoid biosynthesis, including ribulose-bisphosphate carboxylase small-chain gene, pathogenesis-related protein gene, light-harvesting chlorophyll a/b binding protein of photosystem gene, catalase gene, and phenylcoumaran benzylic ether reductase gene et al. Many genes with ESTs similar to photosynthesis, secondary metabolism, and stress-response genes were characterized. The analysis of ESTs indicates that it is a useful approach for isolating Ginkgo genes homologous to known genes. Our results provide new information about mature leaf-specific transcripts of Ginkgo.
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| 41. |
- Xu, Ke-Jun, et al.
(författare)
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Bogoliubov quasiparticle on the gossamer Fermi surface in electron-doped cuprates
- 2023
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Ingår i: Nature Physics. - 1745-2473 .- 1745-2481. ; 19:12, s. 1834-1840
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Tidskriftsartikel (refereegranskat)abstract
- Electron-doped cuprates consistently exhibit strong antiferromagnetic correlations, leading to the prevalent belief that antiferromagnetic spin fluctuations mediate Cooper pairing in these unconventional superconductors. However, early investigations showed that although antiferromagnetic spin fluctuations create the largest pseudogap at hot spots in momentum space, the superconducting gap is also maximized at these locations. This presented a paradox for spin-fluctuation-mediated pairing: Cooper pairing is strongest at momenta where the normal-state low-energy spectral weight is most suppressed. Here we investigate this paradox and find evidence that a gossamer—meaning very faint—Fermi surface can provide an explanation for these observations. We study Nd2–xCexCuO4 using angle-resolved photoemission spectroscopy and directly observe the Bogoliubov quasiparticles. First, we resolve the previously observed reconstructed main band and the states gapped by the antiferromagnetic pseudogap around the hot spots. Within the antiferromagnetic pseudogap, we also observe gossamer states with distinct dispersion, from which coherence peaks of Bogoliubov quasiparticles emerge below the superconducting critical temperature. Moreover, the direct observation of a Bogoliubov quasiparticle permits an accurate determination of the superconducting gap, yielding a maximum value an order of magnitude smaller than the pseudogap, establishing the distinct nature of these two gaps. We propose that orientation fluctuations in the antiferromagnetic order parameter are responsible for the gossamer states.
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| 42. |
- Xu, Ke Jun, et al.
(författare)
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Bogoliubov quasiparticle on the gossamer Fermi surface in electron-doped cuprates
- 2023
-
Ingår i: Nature Physics. - : Springer Nature. - 1745-2473 .- 1745-2481. ; 19:12, s. 1834-1840
-
Tidskriftsartikel (refereegranskat)abstract
- Electron-doped cuprates consistently exhibit strong antiferromagnetic correlations, leading to the prevalent belief that antiferromagnetic spin fluctuations mediate Cooper pairing in these unconventional superconductors. However, early investigations showed that although antiferromagnetic spin fluctuations create the largest pseudogap at hot spots in momentum space, the superconducting gap is also maximized at these locations. This presented a paradox for spin-fluctuation-mediated pairing: Cooper pairing is strongest at momenta where the normal-state low-energy spectral weight is most suppressed. Here we investigate this paradox and find evidence that a gossamer—meaning very faint—Fermi surface can provide an explanation for these observations. We study Nd2–xCexCuO4 using angle-resolved photoemission spectroscopy and directly observe the Bogoliubov quasiparticles. First, we resolve the previously observed reconstructed main band and the states gapped by the antiferromagnetic pseudogap around the hot spots. Within the antiferromagnetic pseudogap, we also observe gossamer states with distinct dispersion, from which coherence peaks of Bogoliubov quasiparticles emerge below the superconducting critical temperature. Moreover, the direct observation of a Bogoliubov quasiparticle permits an accurate determination of the superconducting gap, yielding a maximum value an order of magnitude smaller than the pseudogap, establishing the distinct nature of these two gaps. We propose that orientation fluctuations in the antiferromagnetic order parameter are responsible for the gossamer states.
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| 43. |
- Zha, Jin Lin, et al.
(författare)
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Effects of Northern Hemisphere Annular Mode on terrestrial near-surface wind speed over eastern China from 1979 to 2017
- 2022
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Ingår i: Advances in Climate Change Research. - : Elsevier BV. - 1674-9278 .- 2524-1761. ; 13:6, s. 875-83
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale ocean‒atmosphere circulations (LOACs) have a pronounced effect on the near-surface wind speed (NSWS). In this study, we discussed the contributions of zonal and meridional flows to NSWS changes and identify the possible association between the Northern Hemisphere Annular Mode (NAM) and the NSWS changes over eastern China from 1979 to 2017. Results show that the reduction in NSWS over eastern China was mainly dominated by the weakening of the zonal wind component. NAM has a considerable effect on the NSWS over eastern China. When the NAM exhibits positive phases, the zonal-mean westerly weakens at low-to-mid-latitudes (10°–40°N). Meanwhile, descending flows prevail near 40°N, and ascending flows persist near 65°N in the troposphere. In the lower troposphere, there are northerly anomalies at low-to-mid-latitudes and southerly anomalies at mid-to-high latitudes (40°–70°N). The anomalous meridional flows transport heat from low to high latitudes and weaken the north‒south air temperature gradient. The decreased air temperature gradient over East Asia reduces the pressure gradient near the surface, decreasing NSWS in eastern China. NAM variations could dominate (32.0 ± 15.8)% of the changes in the annual mean NSWS. Nevertheless, the contribution of NAM to the interannual changes of the zonal component in NSWS could reach (45.0 ± 12.9)%.
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| 44. |
- Zhang, Ruyang, et al.
(författare)
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Independent Validation of Early-Stage Non-Small Cell Lung Cancer Prognostic Scores Incorporating Epigenetic and Transcriptional Biomarkers With Gene-Gene Interactions and Main Effects
- 2020
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Ingår i: Chest. - : Elsevier BV. - 0012-3692. ; 158:2, s. 808-819
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question: Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? Study Design and Methods: Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. Results: Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10–17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10–18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. Interpretation: The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival.
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| 45. |
- Zhang, Ruyang, et al.
(författare)
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SIPA1L3 methylation modifies the benefit of smoking cessation on lung adenocarcinoma survival : an epigenomic–smoking interaction analysis
- 2019
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 13:5, s. 1235-1248
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Tidskriftsartikel (refereegranskat)abstract
- Smoking cessation prolongs survival and decreases mortality of patients with non-small-cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome-wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two-stage study design to identify DNA methylation–smoking cessation interactions that affect overall survival for early-stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology-stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation–smoking cessation interaction terms. Interactions with false discovery rate-q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology-specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510 SIPA 1L3 ) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR) interaction = 1.12; 95% confidence interval (CI): 1.07–1.16; P = 4.30 × 10 –7 ]. Further, the effect of smoking cessation on early-stage LUAD survival varied across patients with different methylation levels of cg02268510 SIPA 1L3 . Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34–0.82; P = 4.61 × 10 –3 ) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86–1.70; P = 0.266) of cg02268510 SIPA 1L3 . Moreover, there was an antagonistic interaction between elevated methylation of cg02268510 SIPA 1L3 and smoking cessation (HR interaction = 2.1835; 95% CI: 1.27–3.74; P = 4.46 × 10 −3 ). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510 SIPA 1L3 . The results have implications for not only smoking cessation after diagnosis, but also possible methylation-specific drug targeting.
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| 46. |
- Zhang, Wei, et al.
(författare)
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Activation of nuclear factor-kappa B pathway is responsible for tumor necrosis factor-a-induced up-regulation of endothelin B2 receptor expression in vascular smooth muscle cells in vitro
- 2012
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Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 209:2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- The endothelin B2 (ETB2) receptors are induced in vascular smooth muscle cells (VSMCs) in cardiovascular diseases. We tested if in vitro short-term exposure to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) could up-regulate ETB2 receptors in rat mesenteric arteries, and if this effect is through activation of intracellular nuclear factor-kappa B (NF-kappa B) pathway. The mesenteric arteries were dissected from male Sprague-Dawley rats and the endothelium was removed. The arteries were co-incubated with TNF-alpha in serum-free Dulbecco's modified Eagle's medium. Real-time reverse transcription-PCR, Western blot and immunohistochemical staining were employed to assess the mRNA/protein expression of ETB2 receptors and activation of NF-kappa B pathway. The results showed that, during organ culture. TNF-alpha concentration-dependently enhanced ET52 receptors expression at both mRNA and protein levels, paralleled with activation of NF-kappa B pathway in VSMC. The up-regulated ETB2 receptor expression and NF-kappa B activation could be effectively suppressed by general transcriptional inhibitor actinomycin D, or either of the selective I kappa B kinase inhibitors wedelolactone and IMD-0354. Conclusively, the activation of intracellular NF-kappa B pathway is responsible for the up-regulation of ETB2 receptors induced by short-term exposure to TNF-alpha. This could partly explain the toxic effects of TNF-alpha on VSMCs that account for cardiovascular diseases. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 47. |
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| 48. |
- Zhou, Hui-Ling, et al.
(författare)
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Optimal timing for carbon capture retrofitting in biomass-coal combined heat and power plants in China
- 2021
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Ingår i: Journal of Cleaner Production. - : ELSEVIER SCI LTD. - 0959-6526 .- 1879-1786. ; 293
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Tidskriftsartikel (refereegranskat)abstract
- Industrial decision-makers may wonder about the optimal timing for investing in carbon capture retrofitting in co-firing power plants, faced with uncertain benefits from upcoming China's carbon trading market and potential cost reductions derived from technology innovation. The decision on investment timing relates to the so-called waiting value, considering multiple uncertainties and trade-offs. This article applies a real options-based framework, adapted to deal with the waiting value in the context of multiple uncertainties of carbon market, technical improvements and biomass availability. The problem is solved through an efficient simulation method. The results suggest that the optimal retrofit timing for CCS (carbon capture and storage) in a co-firing CHP will be the year 2033 considering a basic scenario, in which the carbon price is 98 CNY/tonCO(2) (14.5 USS/tonCO(2)) in 2025, the growth rate and volatility are 5% and 7% respectively, and technical improvements are expected every six years and result in a cost reduction of 50%. In addition, we examine the effects of different sub-dimensions in the carbon market and technical improvement on anticipating the retrofit timing. The conclusions of this article provide decision-makers with strategies of adjusting the investment timing in response to their different expectations of market and technology developments. Further practical applications require judgments of future trends made by decision-makers and extensive data of specific cases.
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