| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- de las Fuentes, Lisa, et al.
(author)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Journal article (peer-reviewed)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 3. |
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| 4. |
- Bicak, Mesude, et al.
(author)
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Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB
- 2020
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:10, s. 1581-1591
-
Journal article (peer-reviewed)abstract
- How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.
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| 5. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 6. |
- Liu, Tao, et al.
(author)
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16% efficiency all-polymer organic solar cells enabled by a finely tuned morphology via the design of ternary blend
- 2021
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In: Joule. - : CELL PRESS. - 2542-4351. ; 5:4, s. 914-930
-
Journal article (peer-reviewed)abstract
- A SUMMARY There is an urgent demand for all-polymer organic solar cells (AP-OSCs) to gain higher efficiency. Here, we successfully improve the performance to 16.09% by introducing a small amount of BN-T, a B <- N-type polymer acceptor, into the PM6:PY-IT blend. It has been found that BN-T makes the active layer, based on the PM6:PY-IT:BN-T ternary blend, more crystalline but meanwhile slightly reduces the phase separation, leading to enhancement of both exciton harvesting and charge transport. From a thermodynamic viewpoint, BN-T prefers to reside between PM6 and PY-IT, and the fraction of this fine-tunes the morphology. Besides, a significantly reduced nonradiative energy loss occurs in the ternary blend, along with the coexistence of energy and charge transfer between the two acceptors. The progressive performance facilitated by these improved properties demonstrates that AP-OSCs can possibly comparably efficient with those based on small molecule acceptors, further enhancing the competitiveness of this device type.
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| 7. |
- Luo, Yifei, et al.
(author)
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Technology Roadmap for Flexible Sensors
- 2023
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In: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
-
Research review (peer-reviewed)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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| 8. |
- Wang, Fang, et al.
(author)
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Emerging contaminants: A One Health perspective
- 2024
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In: Innovation. - 2666-6758. ; 5
-
Research review (peer-reviewed)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. |
- Wang, Xing, et al.
(author)
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Validation of prostate cancer risk variants rs10993994 and rs7098889 by CRISPR/Cas9 mediated genome editing
- 2021
-
In: Gene. - : Elsevier BV. - 0378-1119. ; 768
-
Journal article (peer-reviewed)abstract
- GWAS have identified numerous SNPs associated with prostate cancer risk. One such SNP is rs10993994. It is located in the β-microseminoprotein (MSMB) promoter region, mediates MSMB prostate secretion levels, and is linked to mRNA expression changes in both MSMB and the adjacent gene NCOA4. In addition, our previous work showed a second SNP, rs7098889, is in positive linkage disequilibrium with rs10993994 and associated with MSMB expression independent of rs10993994. Here, we generate a series of clones with single alleles removed by double guide RNA (gRNA) mediated CRISPR/Cas9 deletions, through which we demonstrate that each of these SNPs independently and greatly alters MSMB expression in an allele-specific manner. We further show that these SNPs have no substantial effect on the expression of NCOA4. These data demonstrate that a single SNP can have a large effect on gene expression and illustrate the importance of functional validation studies to deconvolute observed correlations. The method we have developed is generally applicable to test any SNP for which a relevant heterozygous cell line is available. Author summary: In pursuing the underlying biological mechanism of prostate cancer pathogenesis, scientists utilized the existence of common single nucleotide polymorphisms (SNPs) in the human genome as genetic markers to perform large scale genome wide association studies (GWAS) and have so far identified more than a hundred prostate cancer risk variants. Such variants provide an unbiased and systematic new venue to study the disease mechanism, and the next big challenge is to translate these genetic associations to the causal role of altered gene function in oncogenesis. The majority of these variants are waiting to be studied and lots of them may act in oncogenesis through gene expression regulation. To prove the concept, we took rs10993994 and its linked rs7098889 as an example and engineered single cell clones by allelic-specific CRISPR/Cas9 deletion to separate the effect of each allele. We observed that a single nucleotide difference would lead to surprisingly high level of MSMB gene expression change in a gene specific and cell-type specific manner. Our study strongly supports the notion that differential level of gene expression caused by risk variants and their associated genetic locus play a major role in oncogenesis and also highlights the importance of studying the function of MSMB encoded β-MSP in prostate cancer pathogenesis.
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| 10. |
- Aalbers, Jelle, et al.
(author)
-
Solar neutrino detection sensitivity in DARWIN via electron scattering
- 2020
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:12
-
Journal article (peer-reviewed)abstract
- We detail the sensitivity of the proposed liquid xenon DARWIN observatory to solar neutrinos via elastic electron scattering. We find that DARWIN will have the potential to measure the fluxes of five solar neutrino components: pp, 7Be, 13N, 15O and pep. The precision of the 13N, 15O and pep components is hindered by the double-beta decay of 136Xe and, thus, would benefit from a depleted target. A high-statistics observation of pp neutrinos would allow us to infer the values of the electroweak mixing angle, sin2 theta w, and the electron-type neutrino survival probability, Pee, in the electron recoil energy region from a few keV up to 200 keV for the first time, with relative precision of 5% and 4%, respectively, with 10 live years of data and a 30 tonne fiducial volume. An observation of pp and 7Be neutrinos would constrain the neutrino-inferred solar luminosity down to 0.2%. A combination of all flux measurements would distinguish between the high- (GS98) and low-metallicity (AGS09) solar models with 2.1-2.5 sigma significance, independent of external measurements from other experiments or a measurement of 8B neutrinos through coherent elastic neutrino-nucleus scattering in DARWIN. Finally, we demonstrate that with a depleted target DARWIN may be sensitive to the neutrino capture process of 131Xe.
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| 11. |
- Andersson, Jennie, 1986, et al.
(author)
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Ship-scale CFD benchmark study of a pre-swirl duct on KVLCC2
- 2022
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In: Applied Ocean Research. - : Elsevier Ltd. - 0141-1187 .- 1879-1549. ; 123
-
Journal article (peer-reviewed)abstract
- Installing an energy saving device such as a pre-swirl duct (PSD) is a major investment for a ship owner and prior to an order a reliable prediction of the energy savings is required. Currently there is no standard for how such a prediction is to be carried out, possible alternatives are both model-scale tests in towing tanks with associated scaling procedures, as well as methods based on computational fluid dynamics (CFD). This paper summarizes a CFD benchmark study comparing industrial state-of-the-art ship-scale CFD predictions of the power reduction through installation of a PSD, where the objective was to both obtain an indication on the reliability in this kind of prediction and to gain insight into how the computational procedure affects the results. It is a blind study, the KVLCC2, which the PSD is mounted on, has never been built and hence there is no ship-scale data available. The 10 participants conducted in total 22 different predictions of the power reduction with respect to a baseline case without PSD. The predicted power reductions are both positive and negative, on average 0.4%, with a standard deviation of 1.6%-units, when not considering two predictions based on model-scale CFD and two outliers associated with large uncertainties in the results. Among the variations present in computational procedure, two were found to significantly influence the predictions. First, a geometrically resolved propeller model applying sliding mesh interfaces is in average predicting a higher power reduction with the PSD compared to simplified propeller models. The second factor with notable influence on the power reduction prediction is the wake field prediction, which, besides numerical configuration, is affected by how hull roughness is considered. © 2022 The Authors
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| 12. |
- Chai, J., et al.
(author)
-
A robust equatorial Pacific westerly response to tropical volcanism in multiple models
- 2020
-
In: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894. ; 55, s. 3413-3429
-
Journal article (peer-reviewed)abstract
- After each of the 1963 Agung, 1982 El Chichon, and 1991 Pinatubo eruptions, an El Nino was observed. The increased likelihood of an El Nino after a tropical eruption has also been found in long-term reconstructed proxy data. Through examining simulations over the last millennium by 11 different models, we show that a tropical volcano eruption can robustly excite a western-to-central equatorial Pacific (WCEP) westerly anomaly at 850 hPa in eight out of the 11 models; such a westerly anomaly is favorable for El Nino development. Under the volcanic forcing, there are significant extratropical continent surface cooling and tropical drying with negative precipitation anomalies over the South-South East Asia (SSEA), West African monsoon, and Intertropical Convergence Zone (ITCZ) regions. This common precipitation suppression response occurs in most of the models. Sensitivity experiments show that a WCEP westerly anomaly can be excited by the tropical land cooling, especially the SSEA cooling induced precipitation suppression rather than by the extratropical land surface cooling. Theoretical results show that a WCEP westerly anomaly is excited due to a Gill response to reduced precipitation over the SSEA and West African monsoon regions; and the SSEA contributes more than the West African monsoon does. The ITCZ weakening, however, excites an easterly wind anomaly. The models with more sensitive convective feedback tend to simulate an El Nino more easily, while a failed simulation of an El Nino after a robust westerly anomaly in some models calls for further studies on these models' delayed responses to radiative forcing induced by volcano eruptions.
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| 13. |
- Chen, Yuqing, et al.
(author)
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Breaking solvation dominance of ethylene carbonate via molecular charge engineering enables lower temperature battery
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
-
Journal article (peer-reviewed)abstract
- Low temperatures severely impair the performance of lithium-ion batteries, which demand powerful electrolytes with wide liquidity ranges, facilitated ion diffusion, and lower desolvation energy. The keys lie in establishing mild interactions between Li+ and solvent molecules internally, which are hard to achieve in commercial ethylene-carbonate based electrolytes. Herein, we tailor the solvation structure with low-ε solvent-dominated coordination, and unlock ethylene-carbonate via electronegativity regulation of carbonyl oxygen. The modified electrolyte exhibits high ion conductivity (1.46 mS·cm−1) at −90 °C, and remains liquid at −110 °C. Consequently, 4.5 V graphite-based pouch cells achieve ~98% capacity over 200 cycles at −10 °C without lithium dendrite. These cells also retain ~60% of their room-temperature discharge capacity at −70 °C, and miraculously retain discharge functionality even at ~−100 °C after being fully charged at 25 °C. This strategy of disrupting solvation dominance of ethylene-carbonate through molecular charge engineering, opens new avenues for advanced electrolyte design.
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| 14. |
- Farnocchia, Davide, et al.
(author)
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International Asteroid Warning Network Timing Campaign: 2019 XS
- 2022
-
In: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
-
Journal article (peer-reviewed)abstract
- As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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| 15. |
- Fenstermacher, M.E., et al.
(author)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
-
In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
-
Journal article (peer-reviewed)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 16. |
- Gao, Mingming, et al.
(author)
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Engineered 2D MXene-based materials for advanced supercapacitors and micro-supercapacitors
- 2024
-
In: Materials Today. - 1369-7021 .- 1873-4103. ; 72, s. 318-358
-
Research review (peer-reviewed)abstract
- The class of two-dimensional transition metal carbides/nitrides/oxycarbides (known as MXenes) has shown great potential in energy storage applications due to their intrinsic layered structure, outstanding electrical conductivity, tunable surface chemistry, and unique physicochemical properties. This review summarizes the latest progresses of MXene-based materials for supercapacitors and micro-supercapacitors. First, state-of-the-art structural engineering strategies for the construction of novel MXene-based electrodes are highlighted, as the electrochemical performance of MXenes is influenced by their structure, such as interlayer spacing and surface functional group density. Furthermore, the charge storage mechanisms of MXene-based electrodes in different electrolytes are discussed to stimulate further design and development of tailored materials for high-performance devices. Moreover, different device fabrication technologies are summarized and the achievements of specific device geometries (e.g., fiber-shape, planar-type, and three-dimensional devices) containing MXene-based materials are critically reviewed. Finally, perspectives and outlook for the development of high-performance MXene-based electrodes in terms of material engineering, performance improvement and device innovation are provided, clearly indicating research directions for next-generation advanced energy storage devices.
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| 17. |
- Gao, Ying, et al.
(author)
-
Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis
- 2024
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In: FASEB Journal. - 0892-6638. ; 38:4
-
Journal article (peer-reviewed)abstract
- The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/β-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed β-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/β-catenin in the epidermis prompted telogen–anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.
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| 18. |
- Grøn, Ole, et al.
(author)
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Acoustic mapping of submerged stone age sites—A HALD approach
- 2021
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In: Remote Sensing. - : MDPI AG. - 2072-4292. ; 13:3
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Journal article (peer-reviewed)abstract
- Acoustic response from lithics knapped by humans has been demonstrated to facilitate effective detection of submerged Stone Age sites exposed on the seafloor or embedded within its sediments. This phenomenon has recently enabled the non-invasive detection of several hitherto unknown submerged Stone Age sites, as well as the registration of acoustic responses from already known localities. Investigation of the acoustic-response characteristics of knapped lithics, which appear not to be replicated in naturally cracked lithic pieces (geofacts), is presently on-going through laboratory experiments and finite element (FE) modelling of high-resolution 3D-scanned pieces. Experimental work is also being undertaken, employing chirp sub-bottom systems (reflection seismic) on known sites in marine areas and inland water bodies. Fieldwork has already yielded positive results in this initial stage of development of an optimised Human-Altered Lithic Detection (HALD) method for mapping submerged Stone Age sites. This paper reviews the maritime archaeological perspectives of this promising approach, which potentially facilitates new and improved practice, summarizes existing data, and reports on the present state of development. Its focus is not reflection seismics as such, but a useful resonance phenomenon induced by the use of high-resolution reflection seismic systems.
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| 19. |
- Guo, Hui-Hui, et al.
(author)
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Alleviation of allergic asthma by rosmarinic acid via gut-lung axis
- 2024
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In: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 126
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Journal article (peer-reviewed)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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| 20. |
- Jin, S. C., et al.
(author)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10
-
Journal article (peer-reviewed)abstract
- Whole-exome sequencing of 250 parent-offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder. In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1AandCTNNB1) met genome-wide significance. We identified two novel monogenic etiologies,FBXO31andRHOB, and showed that theRHOBmutation enhances active-state Rho effector binding while theFBXO31mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in aDrosophilareverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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| 21. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 22. |
- Li, Yongqiang, et al.
(author)
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Activation of locally excavated spoil for utilization in limestone calcined clay cement (LC3)
- 2024
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In: Construction and Building Materials. - 0950-0618. ; 420
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Journal article (peer-reviewed)abstract
- The utilization of clay to produce limestone calcined clay cement (LC3) is limited in China due to environmental concerns related to clay excavation. This study explores the potential to activate the fine-grained clay sourced from excavated spoil in Shenzhen, China for LC3 production. A water washing method was introduced to treat the excavated spoil, enriching the clays’ kaolinite content in a range of 72.4–83.1%. Incorporation of calcined clay with different calcination procedures will modify the hydration rate for aluminate, and the longer calcination after 2 h is detrimental for clay reactivity. Additionally, using excavated spoil calcined at 800 °C with more than 2 h in paste yields compressive strength comparable to that of paste made of ordinary Portland cement (OPC). Calcining at 800 °C for 2 h is the optimal calcination procedure to activate the collected soil. Notably, this activation approach for LC3 production exhibits remarkable environmental and economic benefits, reinforcing the potential for extensive adoption of LC3 within China.
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| 23. |
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| 24. |
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| 25. |
- Liu, Xiaoqing, et al.
(author)
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Exploring the cellulolytic and hemicellulolytic activities of manganese peroxidase for lignocellulose deconstruction
- 2023
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In: Biotechnology for Biofuels and Bioproducts. - 2731-3654. ; 16
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Journal article (peer-reviewed)abstract
- BackgroundA cost-effective pretreatment and saccharification process is a necessary prerequisite for utilizing lignocellulosic biomass (LCB) in biofuel and biomaterials production. Utilizing a multifunctional enzyme with both pretreatment and saccharification functions in a single step for simultaneous biological pretreatment and saccharification process (SPS) will be a green method of low cost and high efficiency. Manganese peroxidase (MnP, EC 1.11.1.13), a well-known lignin-degrading peroxidase, is generally preferred for the biological pretreatment of biomass. However, exploring the role and performance of MnP in LCB conversion will promote the application of MnP for lignocellulose-based biorefineries.ResultsIn this study, we explored the ability of an MnP from Moniliophthora roreri, MrMnP, in LCB degradation. With Mn2+ and H2O2, MrMnP decomposed 5.0 g/L carboxymethyl cellulose to 0.14 mM of reducing sugar with a conversion yield of 5.0 mg/g, including 40 μM cellobiose, 70 μM cellotriose, 20 μM cellotetraose, and 10 μM cellohexaose, and degraded 1.0 g/L mannohexaose to 0.33 μM mannose, 4.08 μM mannotriose, and 4.35 μM mannopentaose. Meanwhile, MrMnP decomposed 5.0 g/L lichenan to 0.85 mM of reducing sugar with a conversion yield of 30.6 mg/g, including 10 μM cellotriose, 20 μM cellotetraose, and 80 μM cellohexose independently of Mn2+ and H2O2. Moreover, the versatility of MrMnP in LCB deconstruction was further verified by decomposing locust bean gum and wheat bran into reducing sugars with a conversion yield of 54.4 mg/g and 29.5 mg/g, respectively, including oligosaccharides such as di- and tri-saccharides. The catalytic mechanism underlying MrMnP degraded lignocellulose was proposed as that with H2O2, MrMnP oxidizes Mn2+ to Mn3+. Subsequently, it forms a complex with malonate, facilitating the degradation of CMC and mannohexaose into reducing sugars. Without H2O2, MrMnP directly oxidizes malonate to hydroperoxyl acetic acid radical to form compound I, which then attacks the glucosidic bond of lichenan.ConclusionThis study identified a new function of MrMnP in the hydrolysis of cellulose and hemicellulose, suggesting that MrMnP exhibits its versatility in the pretreatment and saccharification of LCB. The results will lead to an in-depth understanding of biocatalytic saccharification and contribute to forming new enzymatic systems for using lignocellulose resources to produce sustainable and economically viable products and the long-term development of biorefinery, thereby increasing the productivity of LCB as a green resource.
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| 26. |
- Ma, Wenjun, et al.
(author)
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Responses of soil extracellular enzyme activities and microbial community properties to interaction between nitrogen addition and increased precipitation in a semi-arid grassland ecosystem
- 2020
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 703
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Journal article (peer-reviewed)abstract
- Both atmospheric nitrogen (N) deposition and precipitation can strongly impact below-ground biogeochemical processes. Soil extracellular enzymes activities (EEAs) and microorganisms are considered as the key agents in ecosystem nutrient cycling. However, how the interaction between increasing N deposition and precipitation may affect soil EEAs and microbes remain poorly understood. In a 5-year field experiment in a meadow steppe in northern China, we tested the effects of N addition (N0, 0; N1, 5; N2, 10 g N m−2 yr−1) and increased precipitation (W0, ambient precipitation; W1, increase of 15% ambient precipitation; W2, increase of 30% ambient precipitation) on soil EEAs, microbial and chemical properties. Results showed that their interaction significantly affected all hydrolase activities, except for β-1,4-xylosidase (βX). Furthermore, increased precipitation and N addition interactively affected bacterial gene copies (P ≤ 0.05), and increased precipitation comparatively had a stronger effects. The results on the combination of N addition and increased precipitation showed that increased precipitation alleviated the positive effects of N addition on soil EEAs. This implies that the effects of either treatment alone on grassland biogeochemical processes may be alleviated by their simultaneous occurrence. Our results suggested that soil EEAs were mainly controlled by the content of N and phosphorus (P), and the ratio of C: N and C: P. Therefore, soil element content and stoichiometry could better explain the responses of EEAs to global changes. Moreover, soil microbial communities were mainly controlled by soil P content. Overall, our study highlights that the interaction between N deposition and precipitation may play a vital role in predicting the responses of soil enzyme activities to global changes in grassland ecosystems.
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| 27. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
-
Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 28. |
- Menkveld, Albert J., et al.
(author)
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Nonstandard Errors
- 2024
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In: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Journal article (peer-reviewed)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 29. |
- Ruggeri, Kai, et al.
(author)
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The globalizability of temporal discounting
- 2022
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In: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
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Journal article (peer-reviewed)abstract
- Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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| 30. |
- Shen, Minhao, et al.
(author)
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Effects of exposure time and printing angle on the curing characteristics and flexural strength of ceramic samples fabricated via digital light processing
- 2020
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In: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 46:15, s. 24379-24384
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Journal article (peer-reviewed)abstract
- The development of photosensitive slurries for additive manufacturing has attracted great interest due to their correlation with the final properties of the fabricated parts. This paper focus on the printing quality control in digital light processing (DLP) 3D printing of advanced ceramics. Systematic experiments were performed to assess the effects of the exposure time and printing angle on the three-point bending strength of the fabricated samples. The exposure time affected the bending strength of the printed zirconia ceramic dramatically. When the weak exposure time is 1 s and the strong exposure time is 13 s, the average bending strength can reach 580 MPa while Weibull modulus can reach 8.84. Meanwhile, the printing angle also affected the bending strength mechanical sample printed at 45 degrees exhibits the worst performance.
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| 31. |
- Tang, Weidong, et al.
(author)
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The roles of metal oxidation states in perovskite semiconductors
- 2023
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In: Matter. - : CELL PRESS. - 2590-2393 .- 2590-2385. ; 6:11, s. 3782-3802
-
Research review (peer-reviewed)abstract
- Metal halide perovskites are an emerging materials platform for optoelectronic, spintronic, and thermoelectric applications. The field of perovskite materials and devices has progressed rapidly over the past decade. For halide perovskite materials, a range of physical and chemical properties such as crystal structure, bandgap, charge carrier density, and stability that govern the device functionalities are critically determined by the oxidation states of the B-site metal ions. However, such an important mechanistic connection unique to halide perovskites is not well established, limiting the pace of development in this area. In this review, we identify the roles of metal oxidation states in perovskite semiconductors. The redox reactions leading to these states, and their effects on the materials properties, are clarified. Finally, we suggest routes to improving device efficiency and stability from the perspective of oxidation state control.
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| 32. |
- Wang, Yangong, et al.
(author)
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Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy
- 2024
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In: NATURE MEDICINE. - 1078-8956 .- 1546-170X. ; 30, s. 1395-1405
-
Journal article (peer-reviewed)abstract
- Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making. Using exome sequencing data from one of the largest cohorts of children with cerebral palsy, the genetic diagnostic rates of single-nucleotide and copy number variants were assessed and a sizeable fraction found to be clinically actionable.
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| 33. |
- Wang, Y. G., et al.
(author)
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The Association Study of IL-23R Polymorphisms With Cerebral Palsy in Chinese Population
- 2020
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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 14
-
Journal article (peer-reviewed)abstract
- Background: Cerebral palsy (CP) is a syndrome of non-progressive motor dysfunction caused by early brain development injury. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP. Methods: We recruited 782 children with CP as the case group and 770 healthy children as the control group. The association between IL-23R single nucleotide polymorphisms (SNPs; namely, rs10889657, rs6682925, rs1884444, rs17375018, rs1004819, rs11805303, and rs10889677) and CP was studied by using a case-control method and SHEsis online software. Subgroup analysis based on complications and clinical subtypes was also carried out. Results: There were differences in the allele and genotype frequencies between CP cases and controls at the rs11805303 and rs10889677 SNPs (Pallele = 0.014 and 0.048, respectively; Pgenotype = 0.023 and 0.008, respectively), and the difference in genotype frequency of rs10889677 remained significant after Bonferroni correction (Pgenotype = 0.048). Subgroup analysis revealed a more significant association of rs10889677 with CP accompanied by global developmental delay (Pgenotype = 0.024 after correction) and neonatal encephalopathy (Pgenotype = 0.024 after correction). Conclusion: The present results showed a significant association between IL-23R and CP, suggesting that IL-23R may play a potential role in CP pathogenesis.
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| 34. |
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| 35. |
- Xing, Lei-Lei, et al.
(author)
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Influence of Powder Bed Temperature on the Microstructure and Mechanical Properties of Ti-6Al-4V Alloy Fabricated via Laser Powder Bed Fusion
- 2021
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In: Materials. - : MDPI AG. - 1996-1944. ; 14:9
-
Journal article (peer-reviewed)abstract
- Laser powder bed fusion (LPBF) is being increasingly used in the fabrication of complex-shaped structure parts with high precision. It is easy to form martensitic microstructure in Ti-6Al-4V alloy during manufacturing. Pre-heating the powder bed can enhance the thermal field produced by cyclic laser heating during LPBF, which can tailor the microstructure and further improve the mechanical properties. In the present study, all the Ti-6Al-4V alloy samples manufactured by LPBF at different powder bed temperatures exhibit a near-full densification state, with the densification ratio of above 99.4%. When the powder bed temperature is lower than 400 degrees C, the specimens are composed of a single alpha ' martensite. As the temperature elevates to higher than 400 degrees C, the alpha and beta phase precipitate at the alpha ' martensite boundaries by the diffusion and redistribution of V element. In addition, the alpha/alpha ' lath coarsening is presented with the increasing powder bed temperature. The specimens manufactured at the temperature lower than 400 degrees C exhibit high strength but bad ductility. Moreover, the ultimate tensile strength and yield strength reduce slightly, whereas the ductility is improved dramatically with the increasing temperature, when it is higher than 400 degrees C.
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| 36. |
- Xu, Lei, et al.
(author)
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The Role of Solution Aggregation Property toward High-Efficiency Non-Fullerene Organic Photovoltaic Cells
- 2024
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In: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095.
-
Journal article (peer-reviewed)abstract
- In organic photovoltaic cells, the solution-aggregation effect (SAE) is long considered a critical factor in achieving high power-conversion efficiencies for polymer donor (PD)/non-fullerene acceptor (NFA) blend systems. However, the underlying mechanism has yet to be fully understood. Herein, based on an extensive study of blends consisting of the representative 2D-benzodithiophene-based PDs and acceptor-donor-acceptor-type NFAs, it is demonstrated that SAE shows a strong correlation with the aggregation kinetics during solidification, and the aggregation competition between PD and NFA determines the phase separation of blend film and thus the photovoltaic performance. PDs with strong SAEs enable earlier aggregation evolutions than NFAs, resulting in well-known polymer-templated fibrillar network structures and superior PCEs. With the weakening of PDs' aggregation effects, NFAs, showing stronger tendencies to aggregate, tend to form oversized domains, leading to significantly reduced external quantum efficiencies and fill factors. These trends reveal the importance of matching SAE between PD and NFA. The aggregation abilities of various materials are further evaluated and the aggregation ability/photovoltaic parameter diagrams of 64 PD/NFA combinations are provided. This work proposes a guiding criteria and facile approach to match efficient PD/NFA systems. A systematic study of the representative organic photovoltaic systems shows that the aggregation competition between polymer donor (PD) and non-fullerene acceptor (NFA) is a decisive factor in the phase separation of blend film and thus the photovoltaic performance. Based on 64 PD/NFA combinations, the aggregation ability/photovoltaic parameter heatmaps are plotted, providing a new matching rule for developing high-efficiency PD/NFA systems. image
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| 37. |
- Xue, Qingwen, et al.
(author)
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A Context-Aware Framework for Risky Driving Behavior Evaluation Based on Trajectory Data
- 2023
-
In: IEEE Intelligent Transportation Systems Magazine. - 1939-1390 .- 1941-1197. ; 15:1, s. 70-83
-
Journal article (peer-reviewed)abstract
- Risky driving behaviors are one of the key contributors to traffic accidents. The rapid and accurate identification of them is important to improve the safety of the driving environment. This study introduces a contextaware framework for the evaluation of risky driving behaviors based on trajectory data. It consists of three models to identify the context, determine risky maneuvers, and evaluate risky driving behaviors. We first propose a surrogate-based method to label risky maneuvers considering context factors. Then, the features of driving trajectories are extracted as the input features for the evaluation of risky behavior. Based on the labeling result and maneuver features, supervised machine learning algorithms are leveraged to model their relationships for evaluations. Three feature extraction methods and five classifiers are compared in this article to select the most suitable one. Last, a context-aware evaluation framework is proposed to recognize risky driving behaviors incorporating context. The trajectory data extracted from unmanned aerial vehicles are used to validate the proposed framework. The results show that the accuracy of risky driving behaviors evaluation could reach 97%. The proposed framework in this study can effectively evaluate risky driving behaviors based on trajectory data with the consideration of context factors.
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| 38. |
- Yao, Xiangyu, et al.
(author)
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A highly sensitive bead-based flow cytometric competitive binding assay to detect SARS-CoV-2 neutralizing antibody activity
- 2022
-
In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
-
Journal article (peer-reviewed)abstract
- Accurate detection of SARS-CoV-2 neutralizing antibody (nAb) is critical for assessing the immunity levels after virus infection or vaccination. As fast, cost-effective alternatives to viral infection-based assays, competitive binding (CB) assays were developed to quantitate nAb by monitoring the ability of sera to inhibit the binding of viral spike (S) protein to the angiotensin converting enzyme 2 (ACE2) receptor. Herein, we established a bead-based flow cytometric CB assay and tested the detection performance of six combination models, i.e. immobilized ACE2 and soluble Fc-tagged S1 subunit of S protein (iACE2/S1-Fc), immobilized ACE2 and soluble Fc-tagged receptor binding domain (RBD) of S protein (iACE2/RBD-Fc), immobilized S1 and soluble Fc-tagged ACE2 (iS1/ACE2-Fc), immobilized S1 and soluble His-tagged ACE2 (iS1/ACE2-His), immobilized RBD and soluble Fc-tagged ACE2 (iRBD/ACE2-Fc), and immobilized RBD and soluble His-tagged ACE2 (iRBD/ACE2-His). Using SARS-CoV-2 monoclonal antibodies and sera of convalescent COVID-19 patients and vaccinated subjects, the combination models iACE2/RBD-Fc, iACE2/S1-Fc and iS1/ACE2-His were identified to be able to specifically detect SARS-CoV-2 nAb, among which iACE2/RBD-Fc model showed the highest sensitivity, superior to a commercial SARS-CoV-2 surrogate virus neutralization test (sVNT) ELISA kit. Further studies demonstrated that the sensitivity and specificity of CB assays were affected by the tag of ACE2, type of spike and method of measuring binding rate between ACE2 and spike. Moreover, the iACE2/RBD-Fc model showed good performance in detecting kinetic development of nAb against both the prototype SARS-CoV-2 strain and an omicron variant of SARS-CoV-2 in people immunized by an inactivated SARS-CoV-2 vaccine, and the results of iACE2/RBD-Fc model are correlated well with those of live virus-based and pseudovirus-based neutralization tests, demonstrating the potential to be developed into a highly sensitive, specific, versatile and high-throughput method for detecting SARS-CoV-2 nAb in clinical practice.
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| 39. |
- Zhang, Lixiu, et al.
(author)
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Advances in the Application of Perovskite Materials
- 2023
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In: NANO-MICRO LETTERS. - : SHANGHAI JIAO TONG UNIV PRESS. - 2311-6706. ; 15:1
-
Research review (peer-reviewed)abstract
- Nowadays, the soar of photovoltaic performance of perovskite solar cells has set off a fever in the study of metal halide perovskite materials. The excellent optoelectronic properties and defect tolerance feature allow metal halide perovskite to be employed in a wide variety of applications. This article provides a holistic review over the current progress and future prospects of metal halide perovskite materials in representative promising applications, including traditional optoelectronic devices (solar cells, light-emitting diodes, photodetectors, lasers), and cutting-edge technologies in terms of neuromorphic devices (artificial synapses and memristors) and pressure-induced emission. This review highlights the fundamentals, the current progress and the remaining challenges for each application, aiming to provide a comprehensive overview of the development status and a navigation of future research for metal halide perovskite materials and devices.
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| 40. |
- Zhang, Ya Hong, et al.
(author)
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AβPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease
- 2024
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In: Matrix Biology. - 0945-053X. ; 129, s. 29-43
-
Journal article (peer-reviewed)abstract
- As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AβPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AβPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.
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| 41. |
- Zheng, Shao Fei, et al.
(author)
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An inverse optimization of turbulent flow and heat transfer for a cooling passage with hierarchically arranged ribs in turbine blades
- 2024
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In: International Journal of Heat and Mass Transfer. - 0017-9310. ; 220
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Journal article (peer-reviewed)abstract
- Owing to the limited cold-air amount and pressure in supply systems, high-efficient heat transfer with low-level friction loss is highly desired for cooling units of a turbine blade. To exploit the potential improvement of hierarchically arranged ribs in cooling passages proposed previously, multi-parameter optimizations for rib arrangements are implemented by integrating the simplified conjugate-gradient algorithm with the turbulent flow and heat transfer model. Rib heights as design variables are optimized with various performance indices as objective functions at a fixed Re. The optimizations confirm that using the wall temperature difference and Nu as the objective function, respectively, a limited heat transfer improvement is achieved with a greatly increased friction loss. Taking the overall performance factor as the objective function, different optimal designs at different constraint conditions possess hierarchical characteristics. A significant friction loss reduction of 52.1%, 54.7%, and 54.8%, is achieved with a moderate heat transfer loss of 10.9%, 7.0%, and 2.3%. Despite different thermal and friction performances, their overall performances are consistent with a remarkable increase of 13.9%, 21.2%, and 27.3%. Finally, the optimization strategy coupling the multi-parameter optimization and hierarchical scheme is confirmed as effective for enhancing the thermohydraulic performance of convective heat transfer systems with perturbation elements.
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| 42. |
- Zheng, Shao Fei, et al.
(author)
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Effect of wall curvature on heat transfer and hydrodynamics in a ribbed cooling passage
- 2024
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In: International Journal of Heat and Fluid Flow. - 0142-727X. ; 106
-
Journal article (peer-reviewed)abstract
- Simplified rectangular ribbed cooling passages with a flat wall are extensively considered in exploring the internal cooling features of turbine blades, but the realistic blade has a twisted shape inherently. The effects induced by the curved wall have not been clarified in detail. In this work, adopting a verified v2f turbulence model, numerical investigations are completed to evaluate the effects of the curved wall on the internal cooling characteristics of a ribbed channel. Adopting the unified ribbed channel, flat, convex, and concave walls with distinct curvatures are comprehensively evaluated and compared in a wide Re range for the turbulent flow and heat transfer features as well as the flow and thermal performance. It is found that using the flat wall, ribs can typically induce recirculation vortices having a two-dimensional nature. In contrast, the curved wall significantly contributes to the counter-rotating vortex pairs on the spanwise plane. Combined with recirculation vortices offered by the ribs, the turbulent flow of the cooling channel with the curved wall has a remarkable three-dimensional feature. Hence, the turbulent activity and fluid mixing are enhanced greatly along with the raised heat transfer enhancement and friction loss. Particularly, the convex wall with a curvature of K = 4 provides 28.6 % higher heat transfer performance (Nu/Nu0) but 88.4 % higher resistance (f/f0) than the flat wall. Considering the overall cooling performance, the concave wall with a relatively small curvature is suggested with an improvement of up to 32.8 % concerning the factor (Nu/Nu0)/(f/f0) and 9.5 % on (Nu/Nu0)/(f/f0)1/3. Finally, it is highlighted that considering the effect of the wall curvature, the current study stimulates the mechanistic understanding and provides a design guideline for high-performance blade internal cooling.
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