| 1. |
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- He, Wang, et al.
(författare)
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Fast Power Density Assessment of 5G Mobile Handset Using Equivalent Currents Method
- 2021
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Ingår i: IEEE Transactions on Antennas and Propagation. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-926X .- 1558-2221. ; 69:10, s. 6857-6869
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Tidskriftsartikel (refereegranskat)abstract
- As the fifth-generation (5G) mobile communication is utilizing millimeter-wave (mmWave) frequency bands, electromagnetic field (EMF) exposure emitted from a 5G mmWave mobile handset should be evaluated and compliant with the relevant EMF exposure limits in terms of peak spatial-average incident power density (PD). In this work, a fast PD assessment method for a 5G mmWave mobile handset using the equivalent current (EQC) method is proposed. The EQC method utilizes the intermediate-field (IF) data collected by a spherical measurement system to reconstruct the EQCs over a reconstruction surface and then computes the PD in close proximity of the mobile handset with acceptable accuracy. The performance of the proposed method is evaluated using a mmWave mobile handset mock-up equipped with four quasi-Yagi antennas. The assessed PD results are compared with those computed using full-wave simulations and also those measured with a planar near-field (NF) scanning system. In addition, three influencing factors related to the accuracy of the EQC method, namely, the angular resolution, the phase error, and the handset position in the IF measurements, are also analyzed. The proposed method is a good candidate for fast PD assessment of EMF exposure compliance testing in the mmWave frequency range.
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| 4. |
- He, Wang, et al.
(författare)
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Implications of Incident Power Density Limits on Power and EIRP Levels of 5G Millimeter-Wave User Equipment
- 2020
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Ingår i: IEEE Access. - : Institute of Electrical and Electronics Engineers (IEEE). - 2169-3536. ; 8, s. 148214-148225
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Tidskriftsartikel (refereegranskat)abstract
- User equipment (UE) is required to comply with the relevant radio frequency (RF) electromagnetic field (EMF) exposure limits, which are of relevance to establish the maximum permissible transmitted power and the maximum equivalent isotropically radiated power (EIRP). Recently, international RF EMF exposure guidelines, such as those published by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) as well as by the IEEE, have been updated. In this paper, the implications of the revised incident power density limits are investigated in terms of maximum permissible transmitted power and the maximum EIRP for devices operating in close proximity of the user. A similar analysis is conducted according to the US Federal Communications Commission (FCC) regulation on RF exposure. EMF compliance of UE is studied by means of numerical modelling of patch antenna arrays of different array sizes taking into consideration of possible beam-steering operations, at frequencies ranging from 10 GHz to 100 GHz. The results are compared with the 3rd Generation Partnership Project (3GPP) requirements on the total radiated power (TRP) and EIRP levels. The present implications of the incident power density limits for 5G millimeter-wave UE will give valuable insights to mobile equipment manufacturers, network operators, and standardization bodies.
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| 5. |
- Li, Doudou, et al.
(författare)
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Gut microbiota-derived metabolite trimethylamine-N-oxide and multiple health outcomes : an umbrella review and updated meta-analysis
- 2022
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 116:1, s. 230-243
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Forskningsöversikt (refereegranskat)abstract
- Background: Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO concentrations are linked to a wide range of health outcomes.Objectives: This study aimed to summarize health outcomes related to circulating TMAO concentrations.Methods: We searched the Embase. Medline, Web of Science, and Scopus databases from inception to 15 February, 2022 to identify and update meta-analyses examining the associations between 'TAO and multiple health outcomes. For each health outcome, we estimated the summary effect size. 95% prediction CI. between-study heterogeneity. evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations.Results: This umbrella review identified 24 meta-analyses that investigated the association between circulating 'TAO concentrations and health outcomes including all-cause mortality, cardiovascular diseases (CVDs), diabetes mellitus (DM), cancer. and renal function. We updated these meta-analyses by including a total of 82 individual studies on 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found 6 (33%) associations (i.e., all-cause mortality, CVD mortality, major adverse cardiovascular events, hypertension. DM, and glomerular filtration rate) to present highly suggestive evidence.Conclusions: TMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension. CVD, DM. cancer, and kidney function. Further studies are needed to investigate whether circulating 'MAO concentrations could be an intervention target for chronic disease.
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| 6. |
- 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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| 7. |
- Yu, Wenjin, et al.
(författare)
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Deep Learning-Based Classification of Cancer Cell in Leptomeningeal Metastasis on Cytomorphologic Features of Cerebrospinal Fluid
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope.Objective: This study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage.Method: The cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly.Results: With respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists.Conclusion: A deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer’s primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.
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| 8. |
- Zhang, Zhi, et al.
(författare)
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Customized Structural Color Filters by Pixel-Level Electrothermal Regulation
- 2023
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Ingår i: Laser & Photonics reviews. - : Wiley. - 1863-8880 .- 1863-8899. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Reflective structural colors have backlight-free supremacy and can provide energy-efficient and environmental-friendly color production for many applications. However, they are hindered by the complex process and incorrect colors after fabrication. Here, a pixelated electrothermal oxidation technique is proposed that can precisely tailor and produce reflective structural colors covering the entire visible range, providing the possibility for customized structural color filter arrays from a titanium canvas. Furthermore, as a demonstration, a photonic-firework-like color filter array is achieved in a single step via thermal engineering. Based on this one-step-forming color array, a computational spectrometer is also realized featuring a resolvability of 10 nm and operating bandwidth covering the whole visible range. Considering its compactness and mass production capability, this method has numerous potential applications in, e.g., imaging, anti-counterfeiting, printing, color display, and spectroscopy.
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| 9. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 10. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 11. |
- Abd Nikooie Pour, Mina, et al.
(författare)
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Results of the Ontology Alignment Evaluation Initiative 2022
- 2022
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Ingår i: CEUR Workshop Proceedings. - : CEUR-WS. ; , s. 84-128, s. 84-128
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Konferensbidrag (refereegranskat)abstract
- The Ontology Alignment Evaluation Initiative (OAEI) aims at comparing ontology matching systems on precisely defined test cases. These test cases can be based on ontologies of different levels of complexity and use different evaluation modalities. The OAEI 2022 campaign offered 14 tracks and was attended by 18 participants. This paper is an overall presentation of that campaign. © 2022 Copyright for this paper by its authors.
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| 12. |
- Abd Nikooie Pour, Mina, et al.
(författare)
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Results of the Ontology Alignment Evaluation Initiative 2023
- 2023
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Ingår i: Proceedings of the 18th International Workshop on Ontology Matching co-located with the 22nd International Semantic Web Conference (ISWC 2023), Athens, Greece, November 7, 2023.. - : CEUR Workshop Proceedings. ; , s. 97-139
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Konferensbidrag (refereegranskat)
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| 13. |
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| 14. |
- Cai, Jing, et al.
(författare)
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Size-segregated particle number and mass concentrations from different emission sources in urban Beijing
- 2020
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:21, s. 12721-12740
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Tidskriftsartikel (refereegranskat)abstract
- Although secondary particulate matter is reported to be the main contributor of PM2.5 during haze in Chinese megacities, primary particle emissions also affect particle concentrations. In order to improve estimates of the contribution of primary sources to the particle number and mass concentrations, we performed source apportionment analyses using both chemical fingerprints and particle size distributions measured at the same site in urban Beijing from April to July 2018. Both methods resolved factors related to primary emissions, including vehicular emissions and cooking emissions, which together make up 76% and 24% of total particle number and organic aerosol (OA) mass, respectively. Similar source types, including particles related to vehicular emissions (1.6 +/- 1.1 mu gm(-3); 2.4 +/- 1.8 x 10(3) cm(-3) and 5.5 +/- 2.8 x 10(3) cm(-3) for two traffic-related components), cooking emissions (2.6 +/- 1.9 mu gm(-3) and 5.5 +/- 3.3 x 10(3) cm(-3)) and secondary aerosols (51 +/- 41 mu gm(-3) and 4.2 +/- 3.0 x 10(3) cm(-3)), were resolved by both methods. Converted mass concentrations from particle size distributions components were comparable with those from chemical fingerprints. Size distribution source apportionment separated vehicular emissions into a component with a mode diameter of 20 nm (traffic-ultrafine) and a component with a mode diameter of 100 nm (traffic-fine). Consistent with similar day- and nighttime diesel vehicle PM2.5 emissions estimated for the Beijing area, traffic-fine particles, hydrocarbon-like OA (HOA, traffic-related factor resulting from source apportionment using chemical fingerprints) and black carbon (BC) showed similar diurnal patterns, with higher concentrations during the night and morning than during the afternoon when the boundary layer is higher. Traffic-ultrafine particles showed the highest concentrations during the rush-hour period, suggesting a prominent role of local gasoline vehicle emissions. In the absence of new particle formation, our re-sults show that vehicular-related emissions (14% and 30% for ultrafine and fine particles, respectively) and cooking-activity-related emissions (32 %) dominate the particle number concentration, while secondary particulate matter (over 80 %) governs PM2.5 mass during the non-heating season in Beijing.
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| 15. |
- 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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| 16. |
- El-Serafi, Ahmed, 1977-, et al.
(författare)
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Vitamin D levels and busulphan kinetics in patients undergoing hematopoietic stem cell transplantation, a multicenter study
- 2021
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Ingår i: Bone Marrow Transplantation. - : SPRINGERNATURE. - 0268-3369 .- 1476-5365. ; 56, s. 807-817
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P < 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.
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| 17. |
- Ge, Xiaodong, et al.
(författare)
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Amelioration of type 2 diabetes by the novel 6, 8-guanidyl luteolin quinone-chromium coordination via biochemical mechanisms and gut microbiota interaction
- 2023
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Ingår i: JOURNAL OF ADVANCED RESEARCH. - : Elsevier. - 2090-1232 .- 2090-1224. ; 46, s. 173-188
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activ-ities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored.Objectives: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mel-litus (T2DM) mice.Methods: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota compo-sition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was con-ducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota.Results: The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pan-creatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxi-some proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation.Conclusion: GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.
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| 18. |
- Gopalakrishnan, Pavithra, et al.
(författare)
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Peak Demand Shaving Based on Solar and Load Forecasting at Port of Gavle
- 2022
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Ingår i: 2022 17th International Conference on Probabilistic Methods Applied to Power Systems, PMAPS 2022. - : Institute of Electrical and Electronics Engineers (IEEE).
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Konferensbidrag (refereegranskat)abstract
- Solar energy is considered as one of the most promising solutions to prevent climate change, and optimal utilization of solar energy contributes to reducing dependence on non-renewable energy sources. Distributed generation can help support the delivery of clean and reliable power to consumers. In this paper, an Energy Management System (EMS) is developed along with load and Photovoltaic (PV) generation forecasting to perform peak shaving of electricity demand. The results from the proposed method are implemented in a real case study, in Port of Gavle in Sweden. Total revenue generated from services of peak-shaving and frequency regulation is maximum in the scenario considering high PV generation and high consumption on a selected experimental day in July. The results show that PV-battery storage systems are effective options to increase the integration of renewable energies in the grid, flatten the load, and achieve stabilized operation.
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| 19. |
- He, Junjing, et al.
(författare)
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Application of soft constrained machine learning algorithms for creep rupture prediction of an austenitic heat resistant steel Sanicro 25
- 2023
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Ingår i: JOURNAL OF MATERIALS RESEARCH AND TECHNOLOGY-JMR&T. - : Elsevier BV. - 2238-7854. ; 22, s. 923-937
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Tidskriftsartikel (refereegranskat)abstract
- Creep rupture extrapolation is crucial for high-temperature materials served in power plants. Many analytical models can be used for creep rupture analysis, and fundamental models are also available. Machine learning is also an alternative. However, unphysical prediction curves occur readily in common machine learning algorithms, where one must manipulate the best results or ignore the less satisfactory ones. Using just high regression coefficients and low errors is not enough to obtain high accuracy of the methods. Never-theless, five soft constrained machine learning algorithms (SCMLAs), where soft con-straints, stability analysis by culling long-time or low-stress data, extrapolation from short to long times, and errors of solutions and algorithms are considered, are used for creep rupture prediction in this work. The models can generate reasonable results for fitting all data, extrapolating from short to long times, and stability analysis for Sanicro 25 after a number of tests. The errors of solutions for all the analyses are in a quite reasonable range, including extrapolation and stability analysis. The average relative standard deviation of the five SCMLAs is less than 2.5% at three times the maximum experimental creep rupture time. Creep rupture strength of the austenitic stainless steel Sanicro 25 can be predicted quantitatively by taking the average predicted stresses of the five SCMLAs. The method can also be used for other high-temperature alloys with similar creep degradation mechanisms.
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| 20. |
- He, Junjing, et al.
(författare)
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The role of strength distributions for premature creep failure
- 2023
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Ingår i: Journal of Materials Research and Technology. - : Elsevier BV. - 2238-7854. ; 25, s. 3444-3457
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Tidskriftsartikel (refereegranskat)abstract
- Premature and unexpected creep damage is a significant concern in high-temperature engineering. Identifying outliers in creep rupture data is essential for assessing the risk of premature creep failure. This study proposes a new method to evaluate premature creep failure using log-logistic distribution fit of prediction errors and outlier positions. Fitting results for seven different alloys were obtained from extrapolation procedures using soft-constrained machine learning algorithms (SCMLAs) and constrained time-temperature parameters (TTPs) based on prior research. A comprehensive statistical analysis was conducted for all materials. The log-logistic distribution was validated as a suitable method for fitting prediction error distributions. Regression plots demonstrate effective residual balance and accurate outlier capture. The best fitting methods were identified based on the width of the distributions. Outlier positions were used to evaluate the probability of premature creep failure quantitatively. For example, a 0.5% probability of observing creep rupture strengths that are approximately 50% lower than the standardized creep stress was found for TP316H, T321H, and high Cr steels SUH616B. These findings offer valuable insights for estimating premature creep failure in materials.
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| 21. |
- He, Kun, et al.
(författare)
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Experimental study on flame characteristics of double fires in a naturally ventilated tunnel : Flame merging, flame tilt angle and flame height
- 2021
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Ingår i: Tunnelling and Underground Space Technology. - : Elsevier Ltd. - 0886-7798 .- 1878-4364. ; 114
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Tidskriftsartikel (refereegranskat)abstract
- A series of fire tests was carried out to investigate the diffusion flame characteristics of double fires generated from separated burners in a naturally ventilated tunnel, considering different heat release rates and fire separation distances. The results show that the flame tilt angle, as well as the horizontal projected flame length, first increases with fire separation distance and then remains constant, but the vertical flame length first decreases and then remains constant, which is different from two fires in free spaces where flames do not tilt when the separation distance is relatively long. This difference is caused by the non-dimensional fire induced air flow velocity in the tunnel, which is mainly related to the tunnel cross-section dimensions and burner radius. Three regions can be identified, i.e. flame vertical merging, plume vertical merging and non-merging with flame tilted. The critical flame merging separation distance, estimated by the flame merging probability, is greater than that of two fires in an open environment due to the fire-induced air flows. The merging flame height is lower than that of a single fire with a same heat release rate. A correlation was proposed to estimate flame height of two fires in a tunnel by the modified non-dimensional heat release rate using an air entrainment perimeter as the characteristic length. This work enhances the understanding of diffusion flame behaviors of double fires in naturally ventilated tunnels.
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| 22. |
- He, Kun, et al.
(författare)
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Experimental study on the maximum ceiling gas temperature driven by double fires in a tunnel with natural ventilation
- 2024
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Ingår i: Tunnelling and Underground Space Technology. - : Elsevier Ltd. - 0886-7798 .- 1878-4364. ; 144
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Tidskriftsartikel (refereegranskat)abstract
- The maximum gas temperature below the ceiling is an important parameter for tunnel safety. The present study analyzed the characteristics of the maximum excess ceiling gas temperature driven by double fire sources in a naturally ventilated tunnel. A series of small-scale tunnel fire experiments were carried out with different fire separation distances and heat release rates. Theoretical analysis based on the equivalent virtual origin was also performed. The results showed that there exists only one peak gas temperature when the two fire plumes are merged before reaching the ceiling, while two peak gas temperatures can be observed when the two fire plumes are completely separated. The maximum excess gas temperature below the tunnel ceiling gradually decreases with an increasing fire separation distance in the plume merging region (S < Scp). When the fire separation distance increases further (S > Scp), the effect of the fire separation distance on the maximum gas temperature below the ceiling is very limited. Furthermore, a model using an equivalent fire source was proposed to predict the maximum excess gas temperature below the ceiling, considering different plume merging states. The present study contributes to the understanding of the maximum excess gas temperature characteristics of the smoke flow driven by double fires with an equal heat release rate in naturally ventilated tunnels.
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| 23. |
- He, Kun, et al.
(författare)
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Fire spread among multiple vehicles in tunnels using longitudinal ventilation
- 2023
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Ingår i: Tunnelling and Underground Space Technology. - : Elsevier. - 0886-7798 .- 1878-4364. ; 133
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Tidskriftsartikel (refereegranskat)abstract
- The characteristics of fire spread among multiple vehicles in tunnels using longitudinal ventilation were investigated by analyzing the experimental data from a series of fire tests in a 1:15 scale tunnel. Further, a simple theoretical model for gas temperature in a tunnel with multiple fire sources was proposed and used in analysis of the experimental data. The results showed that, for objects (wood piles) placed at a same separating distance downstream of the fire, the fire spread occurred faster and faster along the tunnel. Validation of the simplified temperature model for multiple fire sources was made against both model and full-scale tunnel fire tests. The model was further used to predict the critical conditions for fire spread to the second and third objects. Comparisons with the test data showed that average excess temperature of 465 K (or an equivalent incident heat flux of 18.7 kW/m2) could be used as the criterion for fire spread, and this was verified further by other model-scale tests and full-scale tests. The results showed that the critical fire spread distance monotonously increases with the heat release rate, and decreases with the tunnel perimeter. For multiple fire sources with equivalent heat release rates, as the separation distance between the first two fire sources increases, the critical fire spread distance from the second fire source to the third fire source decreases, but the total fire spread distance from the first fire source to the third one increases. If the total heat release rate at the site of a downstream fire source is greater than that at the former fire source, the critical fire spread distance becomes longer.
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| 24. |
- Hernández Vásquez, Magda, et al.
(författare)
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Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels
- 2021
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Ingår i: EMBO Journal. - : EMBO Press. - 0261-4189 .- 1460-2075. ; 40:12
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Tidskriftsartikel (refereegranskat)abstract
- The lymphatic system is composed of a hierarchical network of fluid absorbing lymphatic capillaries and transporting collecting vessels. Despite distinct functions and morphologies, molecular mechanisms that regulate the identity of the different vessel types are poorly understood. Through transcriptional analysis of murine dermal lymphatic endothelial cells (LECs), we identified Foxp2, a member of the FOXP family of transcription factors implicated in speech development, as a collecting vessel signature gene. FOXP2 expression was induced after initiation of lymph flow in vivo and upon shear stress on primary LECs in vitro. Loss of FOXC2, the major flow-responsive transcriptional regulator of lymphatic valve formation, abolished FOXP2 induction in vitro and in vivo. Genetic deletion of Foxp2 in mice using the endothelial-specific Tie2-Cre or the tamoxifen-inducible LEC-specific Prox1-CreERT2 line resulted in enlarged collecting vessels and defective valves characterized by loss of NFATc1 activity. Our results identify FOXP2 as a new flow-induced transcriptional regulator of collecting lymphatic vessel morphogenesis and highlight the existence of unique transcription factor codes in the establishment of vessel-type-specific endothelial cell identities.
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| 25. |
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| 26. |
- Huaizi, He, et al.
(författare)
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Effect of Process Parameter Settings and Thickness on Microstructures of EBM Produced TI-6Al-4V Alloy : [工艺参数设置和厚度对电子束熔融加工Ti-6Al-4V合金微观结构的影响]
- 2021
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Ingår i: Xiyou jinshu cailiao yu gongcheng. - : Science Press. - 1002-185X. ; 50:2, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- The effect of sample dimensions and process parameters (beam current, scan speed, offset focus and scan length) of electron beam melting (EBM) system on microstructure of the EBM built Ti-6Al-4V alloy was investigated. The microstructure of EBM built Ti-6Al-4V alloy consists of columnar grains of prior β phase. Inside the columnar grain, typical (α+β) structures, namely Widmanstätten α platelets and rod-like β phase formed on the interfaces of the fine α grains, are observed. Grain boundary α layer forms along grain boundary of prior β columnar grain. With the increase of thickness of the test slab, beam energy density and scanning length, the prior β columnar grain grows along the build direction and diameter of which increases. The columnar grain diameter also decreases with the increase in height of the test slab. With increasing the thickness of the test slab and beam energy density, α platelets get coarser.
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| 27. |
- 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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| 28. |
- Kang, Ying, et al.
(författare)
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Weak Bonds Joint Effects Catalyze the Cleavage of Strong C−C Bond of Lignin‐Inspired Compounds and Lignin in Air by Ionic Liquids
- 2020
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Ingår i: ChemSusChem. - : John Wiley & Sons. - 1864-5631 .- 1864-564X. ; 13:22, s. 5945-5953
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of lignin to value‐added aromatics through selective C−C bond cleavage via metal‐free and mild strategies is promising but challenging. It was discovered that the cations of ionic liquids (ILs) could effectively catalyze this kind of strong bond cleavage by forming multiple weak hydrogen bonds, enabling the reaction conducted in air at temperature lower than 373 K without metal‐containing catalysts. The cation [CPMim]+ (1‐propylronitrile‐3‐methylimidazolium) afforded the highest efficiency in C−C bond cleavage, in which high yields (>90 %) of oxidative products were achieved. [CPMim]+ could form three ipsilateral hydrogen bonds with the oxygen atom of C=O and ether bonds at both sides of the C−C bond. The weak bonds joint effects could promote adjacent C−H bond cleave to form free radicals and thereby catalyze the fragmentation of the strong C−C. This work opens up an eco‐friendly and energy‐efficient route for direct valorization of lignin by enhancing IL properties via tuning the cation.
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| 29. |
- Levin, A., et al.
(författare)
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The role of dendrin in IgA nephropathy
- 2023
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 38:2, s. 311-321
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Tidskriftsartikel (refereegranskat)abstract
- Background Immunoglobulin A nephropathy (IgAN) and its systemic variant IgA vasculitis (IgAV) damage the glomeruli, resulting in proteinuria, hematuria and kidney impairment. Dendrin is a podocyte-specific protein suggested to be involved in the pathogenesis of IgAN. Upon cell injury, dendrin translocates from the slit diaphragm to the nucleus, where it is suggested to induce apoptosis and cytoskeletal changes, resulting in proteinuria and accelerated disease progression in mice. Here we investigated gene and protein expression of dendrin in relation to clinical and histopathological findings to further elucidate its role in IgAN/IgAV. Methods Glomerular gene expression was measured using microarray on 30 IgAN/IgAV patients, 5 patients with membranous nephropathy (MN) and 20 deceased kidney donors. Dendrin was spatially evaluated on kidney tissue sections by immunofluorescence (IF) staining (IgAN patients, n = 4; nephrectomized kidneys, n = 3) and semi-quantified by immunogold electron microscopy (IgAN/IgAV patients, n = 21; MN, n = 5; living kidney donors, n = 6). Histopathological grading was performed according to the Oxford and Banff classifications. Clinical data were collected at the time of biopsy and follow-up. Results Dendrin mRNA levels were higher (P = .01) in IgAN patients compared with MN patients and controls and most prominently in patients with preserved kidney function and fewer chronic histopathological changes. Whereas IF staining did not differ between groups, immunoelectron microscopy revealed that a higher relative nuclear dendrin concentration in IgAN patients was associated with a slower annual progression rate and milder histopathological changes. Conclusion Dendrin messenger RNA levels and relative nuclear protein concentrations are increased and associated with a more benign phenotype and progression in IgAN/IgAV patients.
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| 30. |
- Li, Wenyun, et al.
(författare)
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Personalized Microbial Fingerprint Associated with Differential Glycemic Effects of a Whole Grain Rye Intervention on Chinese Adults
- 2024
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Ingår i: Molecular Nutrition & Food Research. - : Wiley-Blackwell. - 1613-4125 .- 1613-4133.
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Tidskriftsartikel (refereegranskat)abstract
- ScopeThis study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an “enterotype - metabolic” model.Methods and resultsA 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis.ConclusionThe work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.
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| 31. |
- Luo, Yang, et al.
(författare)
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Three-dimensional and temperature-dependent electronic structure of the heavy-fermion compound CePt2In7 studied by angle-resolved photoemission spectroscopy
- 2020
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 101:11
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional and temperature-dependent electronic structures of the heavy-fermion superconductor CePt2In7 are investigated. Angle-resolved photoemission spectroscopy using variable photon energy establishes the existence of quasi-two- and three-dimensional Fermi surface topologies. Temperature-dependent 4d-4f on-resonance photoemission spectroscopies data reveal that heavy quasiparticle bands begin to form at a temperature well above the characteristic (coherence) temperature T+. The emergence of low-lying crystal electric field excitation may be responsible for the "relocalization" or the precursor to the establishment of heavy electrons coherence in heavy-fermion compounds. These findings provide critical insight into understanding the hybridization in heavy-fermion systems.
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| 32. |
- Muhl, Lars, et al.
(författare)
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Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes. To define and distinguish fibroblasts from vascular mural cells have remained challenging. Here, using single-cell RNA sequencing and tissue imaging, the authors provide a molecular basis for cell type classification and reveal inter- and intra-organ diversity of these cell types.
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| 33. |
- Muhl, Lars, et al.
(författare)
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The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells : Implications for COVID-19 vascular research
- 2022
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Ingår i: Stem Cell Reports. - : Elsevier. - 2213-6711. ; 17:5, s. 1089-1104
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Tidskriftsartikel (refereegranskat)abstract
- Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is impor-tant to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, andin heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.
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| 34. |
- Ning, Dezhi, et al.
(författare)
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Near Trapping Effect on Wave-Power Extraction by Linear Periodic Arrays
- 2020
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Near trapping is a kind of strong hydrodynamic interaction phenomenon in a regular array under specific incident wave conditions, which causes the excitation force on the structures in the array to change suddenly. In this paper, based on linear potential flow theory, the effects of near trapping on the hydrodynamic interaction and wave-power extraction characteristics of linear periodic arrays composed of the oscillating float type wave energy converters are studied by using the higher-order boundary element method in a frequency domain. The parameters considered include the separation spacing, number of devices, and incident wave direction. It is found that the near trapping significantly reduces the overall wave-power extraction, especially for the cases with a large number of devices, and changes the trend of the power distribution. The occurrence of the near trapping phenomenon depends on the ratio of the separation spacing to the wavelength and the incident wave direction. The results highlight the effective layout of linear arrays under the influence of near trapping, which not only ensures the total production power, but also reduces the power difference among wave energy converters.
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| 35. |
- Osman, Ahmed M., et al.
(författare)
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Radiation Triggers a Dynamic Sequence of Transient Microglial Alterations in Juvenile Brain
- 2020
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 31:9
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Tidskriftsartikel (refereegranskat)abstract
- Cranial irradiation (IR), an effective tool to treat malignant brain tumors, triggers a chronic pro-inflammatory microglial response, at least in the adult brain. Using single-cell and bulk RNA sequencing, combined with histology, we show that the microglial response in the juvenile mouse hippocampus is rapid but returns toward normal within 1 week. The response is characterized by a series of temporally distinct homeostasis-, sensome-, and inflammation-related molecular signatures. We find that a single microglial cell simultaneously upregulates transcripts associated with pro- and anti-inflammatory microglial phenotypes. Finally, we show that juvenile and adult irradiated microglia are already transcriptionally distinct in the early phase after IR. Our results indicate that microglia are involved in the initial stages but may not be responsible for driving long-term inflammation in the juvenile brain.
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| 36. |
- Qiu, Xia, et al.
(författare)
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Individual participant data meta-analysis to compare EPDS accuracy to detect major depression with and without the self-harm item
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of delta = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7-12 (difference range - 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13-15 (all differences - 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10.
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| 37. |
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| 38. |
- Räsänen, Markus, et al.
(författare)
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VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 143:1, s. 65-77
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Tidskriftsartikel (refereegranskat)abstract
- Background:Recent discoveries have indicated that, in the developing heart, sinus venosus and endocardium provide major sources of endothelium for coronary vessel growth that supports the expanding myocardium. Here we set out to study the origin of the coronary vessels that develop in response to vascular endothelial growth factor B (VEGF-B) in the heart and the effect of VEGF-B on recovery from myocardial infarction.Methods:We used mice and rats expressing a VEGF-B transgene, VEGF-B-gene–deleted mice and rats, apelin-CreERT, and natriuretic peptide receptor 3–CreERT recombinase-mediated genetic cell lineage tracing and viral vector–mediated VEGF-B gene transfer in adult mice. Left anterior descending coronary vessel ligation was performed, and 5-ethynyl-2’-deoxyuridine–mediated proliferating cell cycle labeling; flow cytometry; histological, immunohistochemical, and biochemical methods; single-cell RNA sequencing and subsequent bioinformatic analysis; microcomputed tomography; and fluorescent- and tracer-mediated vascular perfusion imaging analyses were used to study the development and function of the VEGF-B–induced vessels in the heart.Results:We show that cardiomyocyte overexpression of VEGF-B in mice and rats during development promotes the growth of novel vessels that originate directly from the cardiac ventricles and maintain connection with the coronary vessels in subendocardial myocardium. In adult mice, endothelial proliferation induced by VEGF-B gene transfer was located predominantly in the subendocardial coronary vessels. Furthermore, VEGF-B gene transduction before or concomitantly with ligation of the left anterior descending coronary artery promoted endocardium-derived vessel development into the myocardium and improved cardiac tissue remodeling and cardiac function.Conclusions:The myocardial VEGF-B transgene promotes the formation of endocardium-derived coronary vessels during development, endothelial proliferation in subendocardial myocardium in adult mice, and structural and functional rescue of cardiac tissue after myocardial infarction. VEGF-B could provide a new therapeutic strategy for cardiac neovascularization after coronary occlusion to rescue the most vulnerable myocardial tissue.
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| 39. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 40. |
- Schoutrop, Esther, et al.
(författare)
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Mesothelin-Specific CAR T Cells Target Ovarian Cancer
- 2021
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 81:11, s. 3022-3035
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Tidskriftsartikel (refereegranskat)abstract
- New therapeutic options for patients with ovarian cancer are urgently needed. Therefore, we evaluated the efficacy of two second-generation mesothelin (MSLN)-directed CAR T cells in orthotopic mouse models of ovarian cancer. Treatment with CAR T cells expressing an MSLN CAR construct including the CD28 domain (M28z) significantly prolonged survival, but no persistent tumor control was observed. Despite lower response rates, MSLN-4-1BB (MBBz) CAR T cells induced long-term remission in some SKOV3-bearing mice. Tumor-infiltrating M28z and MBBz CAR T cells upregulated PD-1 and LAG3 in an antigen-dependent manner while MSLN+ tumor cells expressed the corresponding ligands (PD-L1 and HLA-DR), demonstrating that coin-hibitory pathways impede CAR T-cell persistence in the ovarian tumor microenvironment. Furthermore, profiling plasma soluble factors identified a cluster of M28z- and MBBz-treated mice characterized by elevated T-cell secreted factors that had increased survival, higher CD8(+) T-cell tumor infiltration, less exhausted CAR T-cell phenotypes, and increased HLA-DR expression by tumor cells. Altogether, our study demonstrates the therapeutic potential of MSLN-CAR T cells to treat ovarian cancer. Significance: These findings demonstrate that MSLN-directed CAR T cells can provide antitumor immunity against ovarian cancer.
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| 41. |
- Schoutrop, Esther, et al.
(författare)
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Tuned activation of MSLN-CAR T cells induces superior antitumor responses in ovarian cancer models
- 2023
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Ingår i: Journal for ImmunoTherapy of Cancer. - : BMJ Publishing Group Ltd. - 2051-1426. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limited persistence of functional CAR T cells in the immunosuppressive solid tumor microenvironment remains a major hurdle in the successful translation of CAR T cell therapy to treat solid tumors. Fine-tuning of CAR T cell activation by mutating CD3ζ chain immunoreceptor tyrosine-based activation motifs (ITAMs) in CD19-CAR T cells (containing the CD28 costimulatory domain) has proven to extend functional CAR T cell persistence in preclinical models of B cell malignancies.METHODS: In this study, two conventional second-generation MSLN-CAR T cell constructs encoding for either a CD28 co-stimulatory (M28z) or 4-1BB costimulatory (MBBz) domain and a novel mesothelin (MSLN)-directed CAR T cell construct encoding for the CD28 costimulatory domain and CD3ζ chain containing a single ITAM (M1xx) were evaluated using in vitro and in vivo preclinical models of ovarian cancer. Two ovarian cancer cell lines and two orthotopic models of ovarian cancer in NSG mice were used: SKOV-3 cells inoculated through microsurgery in the ovary and to mimic a disseminated model of advanced ovarian cancer, OVCAR-4 cells injected intraperitoneally. MSLN-CAR T cell treatment efficacy was evaluated by survival analysis and the characterization and quantification of the different MSLN-CAR T cells were performed by flow cytometry, quantitative PCR and gene expression analysis.RESULTS: M1xx CAR T cells elicited superior antitumor potency and persistence, as compared with the conventional second generation M28z and MBBz CAR T cells. Ex vivo M28z and MBBz CAR T cells displayed a more exhausted phenotype than M1xx CAR T cells as determined by co-expression of PD-1, LAG-3 and TIM-3. Furthermore, M1xx CAR T cells showed superior ex vivo IFNy, TNF and GzB production and were characterized by a self-renewal gene signature.CONCLUSIONS: Altogether, our study demonstrates the enhanced therapeutic potential of MSLN-CAR T cells expressing a mutated CD3ζ chain containing a single ITAM for the treatment of ovarian cancer. CAR T cells armored with calibrated activation potential may improve the clinical responses in solid tumors.
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| 42. |
- Tang, Bowen, et al.
(författare)
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Major depressive disorder and cardiometabolic diseases : a bidirectional Mendelian randomisation study
- 2020
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 63:7, s. 1305-1311
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Observational studies have shown a bidirectional association between major depressive disorder (MDD) and cardiometabolic diseases. We conducted a two-sample bidirectional Mendelian randomisation (MR) study to assess the causal associations of MDD with type 2 diabetes, coronary artery disease (CAD) and heart failure and vice versa. Methods We extracted summary-level data for MDD, type 2 diabetes, CAD and heart failure from corresponding published large genome-wide association studies of individuals mainly of European-descent. In total, 96 SNPs for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD and 12 SNPs for heart failure were proposed as instrumental variables at the genome-wide significance level (p < 5 x 10(-8)). The random-effects inverse-variance weighted method was used for the main analyses. Results Genetic liability to MDD was significantly associated with type 2 diabetes and CAD at the Bonferroni-corrected significance level. The ORs of type 2 diabetes and CAD were respectively 1.26 (95% CI 1.10, 1.43; p = 6 x 10(-4)) and 1.16 (95% CI 1.05, 1.29; p = 0.0047) per one-unit increase in log(e) odds of MDD. There was a suggestive association between MDD and heart failure (OR 1.11 [95% CI 1.01, 1.21]; p = 0.033). We found limited evidence supporting causal effects of cardiometabolic diseases on MDD risk in the reverse MR analyses. Conclusions/interpretation The present study strengthened the evidence that MDD is a potential risk factor for type 2 diabetes and CAD. Whether MDD is causally related to heart failure needs further study. Data availability All data included in this study were uploaded as supplements and are also publicly available through published GWASs and open GWAS datasets (UK Biobank, 23andMe and Psychiatric Genomics: https://datashare.is.ed.ac.uk/handle/10283/3203; DIAGRAM: http://diagram-consortium.org/downloads.html; CARDIoGRAMplusCD4: www.cardiogramplusc4d.org/; HERMES: http://www.kp4cd.org/datasets/mi).
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| 43. |
- Vromman, Marieke, et al.
(författare)
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Large-scale benchmarking of circRNA detection tools reveals large differences in sensitivity but not in precision
- 2023
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 20:8, s. 1159-1169
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Tidskriftsartikel (refereegranskat)abstract
- The detection of circular RNA molecules (circRNAs) is typically based on short-read RNA sequencing data processed using computational tools. Numerous such tools have been developed, but a systematic comparison with orthogonal validation is missing. Here, we set up a circRNA detection tool benchmarking study, in which 16 tools detected more than 315,000 unique circRNAs in three deeply sequenced human cell types. Next, 1,516 predicted circRNAs were validated using three orthogonal methods. Generally, tool-specific precision is high and similar (median of 98.8%, 96.3% and 95.5% for qPCR, RNase R and amplicon sequencing, respectively) whereas the sensitivity and number of predicted circRNAs (ranging from 1,372 to 58,032) are the most significant differentiators. Of note, precision values are lower when evaluating low-abundance circRNAs. We also show that the tools can be used complementarily to increase detection sensitivity. Finally, we offer recommendations for future circRNA detection and validation. This study describes benchmarking and validation of computational tools for detecting circRNAs, finding most to be highly precise with variations in sensitivity and total detection. The study also finds over 315,000 putative human circRNAs.
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| 44. |
- Wang, Qisi, et al.
(författare)
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Magnon interactions in a moderately correlated Mott insulator
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Quantum fluctuations in low-dimensional systems and near quantum phase transitions have significant influences on material properties. Yet, it is difficult to experimentally gauge the strength and importance of quantum fluctuations. Here we provide a resonant inelastic x-ray scattering study of magnon excitations in Mott insulating cuprates. From the thin film of SrCuO2, single- and bi-magnon dispersions are derived. Using an effective Heisenberg Hamiltonian generated from the Hubbard model, we show that the single-magnon dispersion is only described satisfactorily when including significant quantum corrections stemming from magnon-magnon interactions. Comparative results on La2CuO4 indicate that quantum fluctuations are much stronger in SrCuO2 suggesting closer proximity to a magnetic quantum critical point. Monte Carlo calculations reveal that other magnetic orders may compete with the antiferromagnetic Néel order as the ground state. Our results indicate that SrCuO2—due to strong quantum fluctuations—is a unique starting point for the exploration of novel magnetic ground states.
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| 45. |
- Weinstock, Joshua S, et al.
(författare)
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Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis.
- 2023
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Ingår i: Nature. - 1476-4687. ; 616:7958, s. 755-763
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis1. These lesions are precursors for blood cancers2-6, but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, butthis effect was not seen inclones withdriver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimentalknockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
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| 46. |
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| 47. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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| 48. |
- Zambrano, Sonia, et al.
(författare)
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Molecular insights into the early stage of glomerular injury in IgA nephropathy using single-cell RNA sequencing
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 101:4, s. 752-765
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Tidskriftsartikel (refereegranskat)abstract
- IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and defined by the presence of IgA-containing immune complexes in the mesangium that induce an inflammation leading to glomerulonephritis. Since we poorly understand early mechanisms of glomerular injury in IgAN we performed single-cell RNA sequencing (scRNA-seq) analysis of glomerulus-associated cells using SMARTseq2-technology at the early stage of IgAN in grouped ddY-mice. Cell-specific molecular signatures unraveled a key role of endothelial cells in the early pathogenesis of IgAN, especially in the recruitment and infiltration of immune cells. Mesangial and podocyte cells demonstrated less molecular changes. Several intraglomerular paracrine pathways were detected, such as mesangial cell-derived Slit3 potentially activating Roboreceptors in podocyte/endothelial cells. Surprisingly, proximal tubular cells were strongly affected at the early stage and potential glomerulo-tubular cell-cell crosstalk pathways were identified. Importantly, many of the cellular transcriptomic signatures identified in this well-established mouse model were also detected in published bulk transcriptomic data in human IgAN. Moreover, we validated the functionality of key cell-cell crosstalk pathways using cell culture models, such as the effect of the Slit-Robo signalling axis. Thus, our study provides important novel molecular insights into the pathogenesis of early IgAN-associated glomerulopathy.
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| 49. |
- Zhang, Fengying, et al.
(författare)
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Effect of synthesis methods on photoluminescent properties for CsPbBr3 nanocrystals : Hot injection method and conversion method
- 2020
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Ingår i: Journal of Luminescence. - : Elsevier BV. - 0022-2313. ; 220
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Tidskriftsartikel (refereegranskat)abstract
- Multiple facile synthetic strategies for all inorganic perovskite CsPbBr3 nanocrystals (NCs) have been established and developed, profiting from their excellent performance and great potential applied in the field of photonic and optoelectronic. Here, CsPbBr3 NCs were synthesized by both hot injection method (method 1) and conversion method (method 2), and the discrepancy of their photophysical properties is elucidated via the complementary studies between time-resolved photoluminescence (TRPL) and transient-absorption (TA) spectroscopy. We found that CsPbBr3 NCs prepared by conversion method exhibited lower PL quantum yield (QY), which was ascribed to the larger partition of the NCs being passivated from the quenchers from the deep trap states. On the other hand, we also observed different radiative recombination rates between two samples which should be due to various trapping/detrapping times prior to the radiative recombination of the charge carriers in two samples. These results provide better guidance for the development and improvement of synthesis methodology for perovskite NCs.
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| 50. |
- Zhang, Fengying, et al.
(författare)
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Microscopic morphology independence in linear absorption cross-section of CsPbBr3 nanocrystalsMicroscopic morphology independence in linear absorption cross-section of CsPbBr3 nanocrystals
- 2021
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Ingår i: SCIENCE CHINA Materials. - : Springer Science and Business Media LLC. - 2095-8226 .- 2199-4501. ; 64:6, s. 1418-1426
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Tidskriftsartikel (refereegranskat)abstract
- Multiple morphologies of colloidal perovskite nanocrystals (NCs) diversify their optical and electronic properties. Among them, the linear absorption cross-section (σ) is a primary parameter to determine their intrinsic photophysical features, and consequently, application potential. Herein, three morphologies of all-inorganic hybrid colloidal perovskite CsPbBr3 NCs, nanocubes (NBs), nanoplatelets (NLs), and nanowires (NWs), were targeted, and their linear σ values were obtained through femtosecond transient absorption (TA) spectroscopy analysis. At high excitation energy well above the bandgap, the σ per particle of all CsPbBr3 NCs linearly increased with the particle volume (VNC) regardless of the morphology with the value of σ400 = 9.45 × 104 cm−1 × VNC (cm2). Density functional theory (DFT) calculation confirmed the negligible influence of shapes on the optical selection rules. The Einstein spontaneous emission coefficients calculated from the σ values define the intrinsic radiative recombination rate. However, reduced size dependence is observed when the excitation energy is close to the bandgap (i.e., at 460 nm) with the value of σ460 = 2.82 × 108 cm0.65 × (VNC)0.45 (cm2). This should be ascribed to the discrete energy levels as well as lower density of states close to the band edge for perovskite NCs. These results provide in-depth insight into the optical characteristics for perovskite NCs.
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