| 1. |
- 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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| 2. |
- Kim, Jae-Young, et al.
(författare)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
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Tidskriftsartikel (refereegranskat)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 3. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 4. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 5. |
- Bolin, Bryce T., et al.
(författare)
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Characterization of the Nucleus, Morphology, and Activity of Interstellar Comet 2I/Borisov by Optical and Near-infrared GROWTH, Apache Point, IRTF, ZTF, and Keck Observations
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:1
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Tidskriftsartikel (refereegranskat)abstract
- We present visible and near-infrared (NIR) photometric and spectroscopic observations of interstellar object (ISO) 2I/Borisov taken from 2019 September 10 to 2019 December 20 using the GROWTH, the Apache Point Observatory Astrophysical Research Consortium 3.5 m, and the NASA Infrared Telescope Facility 3.0 m combined with pre- and postdiscovery observations of 2I obtained by the Zwicky Transient Facility from 2019 March 17 to 2019 May 5. Comparison with imaging of distant solar system comets shows an object very similar to mildly active solar system comets with an outgassing rate of similar to 10(27)mol s(-1). The photometry, taken in filters spanning the visible and NIR range, shows a gradual brightening trend of similar to 0.03 mag day(-1)since 2019 September 10 UTC for a reddish object becoming neutral in the NIR. The light curve from recent and prediscovery data reveals a brightness trend suggesting the recent onset of significant H2O sublimation with the comet being active with super volatiles such as CO at heliocentric distances >6 au consistent with its extended morphology. Using the advanced capability to significantly reduce the scattered light from the coma enabled by high-resolution NIR images from Keck adaptive optics taken on 2019 October 4, we estimate a diameter for 2I's nucleus of less than or similar to 1.4 km. We use the size estimates of 1I/'Oumuamua and 2I/Borisov to roughly estimate the slope of the ISO size distribution, resulting in a slope of similar to 3.4 1.2, similar to solar system comets and bodies produced from collisional equilibrium.
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| 6. |
- Chan, Simon S. M., et al.
(författare)
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Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis : A Pooled Analysis of Five Prospective Cohort Studies
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. 1048-1058
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs).RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI >= 30 kg/m(2)) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I-2 = 0%) compared with normal BMI (18.5 to <25 kg/m(2)). Each 5 kg/m(2) increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I-2 = 0%). Similarly, with each 5 kg/m(2) increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I-2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I-2 = 0%). No associations were observed between measures of obesity and risk of UC.CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
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| 7. |
- Khalili, Hamed, et al.
(författare)
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Diet Quality and Risk of Older-Onset Crohn's Disease and Ulcerative Colitis
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:5, s. 746-753
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To assess the relationship between diet quality and risk of older-onset Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We conducted a prospective cohort study of 83,147 participants from the Swedish Mammography Cohort and the Cohort of Swedish Men. We used food frequency questionnaire to calculate adherence scores to multiple derived health diet patterns: Alternate Healthy Eating Index (AHEI), Healthy Eating Index-2015 (HEI-2015), Healthful Plant-Based Diet Index (HPDI), and modified Mediterranean Diet Score (mMED) at baseline in 1997 in both cohorts. Diagnoses of CD and UC were retrieved from the Swedish Patient Register. We used Cox proportional hazards modeling to estimate the adjusted hazard ratios (HRs) and 95% CIs.FINDINGS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC. Comparing the highest to the lowest quartiles, the adjusted HRs of CD were 0.73 (95% CI, 0.48, 1.12, Ptrend = 0.123) for AHEI; 0.90 (0.57, 1.41, Ptrend = 0.736) for HEI 2015; 0.52 (95% CI 0.32, 0.85, Ptrend = 0.011) for HPDI; and 0.58 (95% CI 0.32, 1.06, Ptrend = 0.044) for mMED. In contrast, we did not observe an association between any diet quality score and risk of UC.INTERPRETATION: We found that several healthy eating patterns were associated with a lower risk of older-onset CD. Our findings provide a rationale for adapting different healthy dietary patterns based on individuals' food preferences and traditions for designing future prevention strategies for IBD.
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| 8. |
- Mahajan, Anubha, et al.
(författare)
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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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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)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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| 9. |
- Niccum, Blake, et al.
(författare)
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Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis : Results From 2 Prospective US Cohort Studies
- 2022
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Ingår i: Inflammatory Bowel Diseases. - : Lippincott-Raven Publishers. - 1078-0998 .- 1536-4844. ; 28:8, s. 1151-1159
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Tidskriftsartikel (refereegranskat)abstract
- Background: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC.Methods: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).Results: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (P-trend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of >= 15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (P-heterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09).Conclusions: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.
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| 10. |
- Prasciolu, Mauro, et al.
(författare)
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On the use of multilayer Laue lenses with X-ray free electron lasers
- 2021
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Ingår i: International Conference on X-Ray Lasers 2020. - : SPIE. - 1996-756X .- 0277-786X. - 9781510646186 ; 11886
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Konferensbidrag (refereegranskat)abstract
- We report on the use of multilayer Laue lenses to focus the intense X-ray Free Electron Laser (XFEL) beam at the European XFEL to a spot size of a few tens of nanometers. We present the procedure to align and characterize these lenses and discuss challenges working with the pulse trains from this unique X-ray source.
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