| 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. |
- 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
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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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| 3. |
- Liu, Junwei, et al.
(author)
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Polymer synergy for efficient hole transport in solar cells and photodetectors
- 2023
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In: Energy & Environmental Science. - : ROYAL SOC CHEMISTRY. - 1754-5692 .- 1754-5706.
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Journal article (peer-reviewed)abstract
- Hole transport materials (HTMs) have greatly advanced the progress of solution-based electronic devices in the past few years. Nevertheless, most devices employing dopant-free organic HTMs can only deliver inferior performance. In this work, we introduced a novel "polymer synergy" strategy to develop versatile dopant-free polymer HTMs for quantum dot/perovskite solar cells and photodetectors. With this synergy strategy, the optical, electrical and aggregation properties of polymer HTMs can be modulated, resulting in complementary absorption, high hole mobility, favorable energy landscape and moderate aggregation. Moreover, a clear orientational transition was observed for the developed HTMs with a 9-fold increase in the face-on/edge-on ratio, providing a highway-like carrier transport for electronic devices, as revealed by in situ characterization and ultrafast transient absorption. With these benefits, the photovoltaic and photodetection performance of quantum dot devices were boosted from 11.8% to 13.5% and from 2.95 x 10(12) to 3.41 x 10(13) Jones (over a 10-fold increase), respectively. Furthermore, the developed polymer HTMs can also significantly enhance the photovoltaic and photodetection performance of perovskite devices from 15.1% to 22.7% and from 2.7 x 10(12) to 2.17 x 10(13)Jones with the same device structure, indicating their great application potential in the emerging optoelectronics.
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| 4. |
- 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.
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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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| 5. |
- Clabbers, Max T. B., et al.
(author)
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MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MALTIR) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88TIR). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88TIR assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MALTIR. We demonstrate via mutagenesis that the MyD88TIR assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88TIR. Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques.
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| 6. |
- Dai, Qile, et al.
(author)
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OTTERS: a powerful TWAS framework leveraging summary-level reference data
- 2023
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.
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| 7. |
- 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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| 8. |
- He, Xin, et al.
(author)
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Worsening of Renal Function Among Hospitalized Patients With Acute Heart Failure: Phenotyping, Outcomes, and Predictors.
- 2022
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In: Mayo Clinic proceedings. - : Elsevier BV. - 1942-5546 .- 0025-6196. ; 97:9, s. 1619-1630
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Journal article (peer-reviewed)abstract
- To define clinical phenotyping and its associated outcome of worsening of renal function (WRF) in hospitalized acute heart failure (AHF) patients.Latent class analysis was performed in 113 AHF patients who developed WRF within 72 hours in the DOSE (Diuretic Optimization Strategies Evaluation) trial (from March 2008 to November 2009) and ROSE-AHF (Renal Optimization Strategies Evaluation in Acute Heart Failure) trial (from September 2010 to March 2013) to identify potential WRF phenotypes. Clinical characteristics and outcome (in-hospital and post-discharge) were compared between different phenotypes.Two WRF phenotypes were identified by latent class analysis, which we named WRF minimally responsive to diuretics (WRF-MRD) and WRF responsive to diuretics (WRF-RD). Among the population, 58 (9.5%) developed WRF-MRD and 55 (9.0%) developed WRF-RD. Patients with WRF-MRD had more comorbidities than WRF-RD. In WRF-MRD, there were an early increase in serum creatinine, a smaller amount of net fluid loss and weight loss, and a higher rate of worsening or persistent heart failure over 72 hours. In contrast, for those with WRF-RD, they had faster in-hospital net fluid loss and weight loss and a better 60-day survival after discharge even compared with patients without WRF (P=.004). Furthermore, baseline chronic obstructive pulmonary disease, diabetes, and cystatin C were independent predictors of WRF-MRD, whereas serum hemoglobin and sodium predicted WRF-RD.Among hospitalized AHF patients, we identified two phenotypes of WRF with distinct response to heart failure treatment, predictors, and short-term prognosis after discharge. The results could help early differentiation of WRF phenotypes in clinical practice.
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| 9. |
- Jo, Donghui, et al.
(author)
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PST-24 : A Zeolite with Varying Intracrystalline Channel Dimensionality
- 2020
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:40, s. 17691-17696
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Journal article (peer-reviewed)abstract
- Herein we report the synthesis, structure solution, and catalytic properties of PST-24, a novel channel-based medium-pore zeolite. This zeolite was synthesized via the excess fluoride approach. Electron diffraction shows that its structure is built by composite cas-zigzag (cas-zz) building chains, which are connected by double 5-ring (d5r) columns. While the cas-zz building chains are ordered in the PST-24 framework, the d5r columns adopt one of two possible arrangements; the two adjacent d5r columns are either at the same height or at different heights, denoted arrangements S and D, which can be regarded as open and closed valves that connect the channels, respectively. A framework with arrangement D only has a 2D 10-ring channel system, whereas that with arrangement S only contains 3D channels. In actual PST-24 crystals, the open and closed valves are almost randomly dispersed to yield a zeolite framework where the channel dimensionality varies locally from 2D to 3D.
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| 10. |
- Lin, Qibin, et al.
(author)
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Crack coalescence in rock-like specimens with two dissimilar layers and pre-existing double parallel joints under uniaxial compression
- 2021
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In: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier. - 1365-1609 .- 1873-4545. ; 139
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Journal article (peer-reviewed)abstract
- Layered rock masses with joints are widely found in nature. Their mechanical behavior plays a key role in rock engineering applications. However, previous studies have concentrated on the single lithologic layer, and few studies have reported the crack coalescence mechanism in layered rock masses with joints. In this study, uniaxial compression tests were performed on jointed rock-like specimens with two dissimilar layers. The acoustic emission (AE) and the digital image correlation (DIC) techniques are employed to investigate the crack coalescence process of specimens with two dissimilar layers. The influence of the joint angle and rock bridge angle on the mechanical behavior and failure processes in layered rock masses is investigated. The results show that the peak strength is associated with the joint angle and the rock bridge angle. Seven types of crack coalescence have been identified in the specimens, which are not only related to the joint angle and the rock bridge angle but also influenced by the rock layers. Cracks easily coalesce when the joint angle and the rock bridge angle are small. However, when the joint angle and the rock bridge angle are larger, it is difficult for cracks to initiate and propagate in the layer with higher strength. The failure mechanism of the specimens is primarily caused by crack propagation in the layer with lower strength.
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