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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
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| 4. |
- Dolinska, Monika, et al.
(författare)
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Characterization of Bone Marrow Niche in Chronic Myeloid Leukemia Patients Identifies CXCL14 as a New Therapeutic Option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long-term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 5. |
- Dolinska, Monika, et al.
(författare)
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Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 6. |
- Han, Meng, et al.
(författare)
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Experimental study of the effect of air split ratio on thermoacoustic instability in a centrally-staged swirl burner
- 2022
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Ingår i: Physics of Fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 34:6
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Tidskriftsartikel (refereegranskat)abstract
- This study focuses on one of the critical design parameters of lean premixed (LPM) combustors-the air split ratio (ASR) between the pilot and main stages. The effect of the air split ratio on thermoacoustic instability is experimentally studied based on a centrally staged model combustor. It is found that the thermoacoustic instability is suppressed with the ASR higher than 20%. The acoustic modes of ASR lower than 20% are dominated by the main stage mode, while the others are controlled by the pilot stage mode. The time-averaged flame shapes and the flame dynamics are processed and discussed. With the increase in ASR, the pilot flame becomes longer, whereas the main flame becomes shorter. Meanwhile, the pilot and main flames become less separated. Moreover, the flame in the outer shear layer (OSL) is extinguished, which is the key to suppressing the thermoacoustic instability. The flame with lower ASR exhibits large-scale periodic axial motion of flame dynamics. The flow fields of ASR = 15% (unstable) and ASR = 30% (stable) are analyzed and discussed to help reveal the differences in thermoacoustic instability between the two cases. It is found that the primary recirculation zone is smaller with ASR = 30%. Higher vorticity and strain rate distributions found in the OSL are believed to quench the flame there. The present study illustrates that a higher air split ratio improves the thermoacoustic stability, which is helpful in designing LPM combustors.
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| 7. |
- Khalili, Bita, et al.
(författare)
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Associations between common genetic variants and income provide insights about the socioeconomic health gradient
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a genome-wide association study (GWAS) on income among individuals of European descent and leveraged the results to investigate the socio-economic health gradient (N=668,288). We found 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes. Our GWAS-derived polygenic index captures 1 - 4% of income variance, with only one-fourth attributed to direct genetic effects. A phenome-wide association study using this polygenic index showed reduced risks for a broad spectrum of diseases, including hypertension, obesity, type 2 diabetes, coronary atherosclerosis, depression, asthma, and back pain. The income factor showed a substantial genetic correlation (0.92, s.e. = .006) with educational attainment (EA). Accounting for EA's genetic overlap with income revealed that the remaining genetic signal for higher income related to better mental health but reduced physical health benefits and increased participation in risky behaviours such as drinking and smoking.
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| 8. |
- Liu, Dongjie, et al.
(författare)
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Enhancing choice-set generation and route choice modeling with data- and knowledge-driven approach
- 2024
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Ingår i: Transportation Research, Part C: Emerging Technologies. - 0968-090X. ; 162
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Tidskriftsartikel (refereegranskat)abstract
- Two central and interconnected problems arise in the specification of a ‘‘complete’’ path-based route choice model: choice-set generation and choice from a choice set. Choice-set generation poses a significant challenge in personalization and the enumeration of the full choice set with large size. Despite the continued prevalence of classic econometric models for modeling choices within a given set, this requirement of knowledge-driven modeling necessitates explicit model structures and intricate domain knowledge, which may result in practical biases. In this study, a Conditional Variational AutoEncoder (CVAE)-based choice set generation model is developed, which approximates the probability distribution of the underlying choice set generation process conditional on individual and OD characteristics without relying on expert knowledge. In order to facilitate a friendly integration between knowledge-driven econometric and machine learning approaches, a neural-embedded route choice model (IAP-NERCM) with implicit availability/perception (IAP) of choice alternatives is proposed to automatically capture the heterogeneity of taste parameters without assuming any a priori relationship. Results based on synthetic data show that the proposed models are capable of reproducing the pre-defined coefficients. Field data of GPS data collected in Toyota City is used to future test the proposed models compared to classical statistical models. Results indicate that IAP-NERCM exhibits the ability to recover underlying taste function and achieves the best performance in terms of goodness-of-fit, predictability, and estimation time.
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| 9. |
- Wayne, Greg, et al.
(författare)
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Principles of Systems Biology, No. 11
- 2016
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Ingår i: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 3:5, s. 406-410
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Tidskriftsartikel (refereegranskat)abstract
- This month: AI that learns patterns and facts, new protein-RNA and protein-protein relationships, engineering signaling and metabolism, and more variants of Cas9.
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