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Sökning: WFRF:(Hong Chen)

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  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • 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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  • 2019
  • Tidskriftsartikel (refereegranskat)
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  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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  • Aad, G, et al. (författare)
  • 2015
  • swepub:Mat__t
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  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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  • Aad, G., et al. (författare)
  • 2015
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 112:9
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :5
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 112:20
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G., et al. (författare)
  • 2014
  • Tidskriftsartikel (refereegranskat)
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  • Aad, G, et al. (författare)
  • Determination of spin and parity of the Higgs boson in the [Formula: see text] decay channel with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of the spin and parity quantum numbers of the Higgs boson in the [Formula: see text] final state are presented, based on proton-proton collision data collected by the ATLAS detector at the Large Hadron Collider, corresponding to an integrated luminosity of 20.3 fb[Formula: see text] at a centre-of-mass energy of [Formula: see text] TeV. The Standard Model spin-parity [Formula: see text] hypothesis is compared with alternative hypotheses for both spin and CP. The case where the observed resonance is a mixture of the Standard-Model-like Higgs boson and CP-even ([Formula: see text]) or CP-odd ([Formula: see text]) Higgs boson in scenarios beyond the Standard Model is also studied. The data are found to be consistent with the Standard Model prediction and limits are placed on alternative spin and CP hypotheses, including CP mixing in different scenarios.
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  • Aad, G, et al. (författare)
  • Measurements of fiducial cross-sections for [Formula: see text] production with one or two additional b-jets in pp collisions at [Formula: see text]=8 TeV using the ATLAS detector.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Fiducial cross-sections for [Formula: see text] production with one or two additional b-jets are reported, using an integrated luminosity of 20.3 fb[Formula: see text] of proton-proton collisions at a centre-of-mass energy of 8 TeV at the Large Hadron Collider, collected with the ATLAS detector. The cross-section times branching ratio for [Formula: see text] events with at least one additional b-jet is measured to be 950 [Formula: see text] 70 (stat.) [Formula: see text] (syst.) fb in the lepton-plus-jets channel and 50 [Formula: see text] 10 (stat.) [Formula: see text] (syst.) fb in the [Formula: see text] channel. The cross-section times branching ratio for events with at least two additional b-jets is measured to be 19.3 [Formula: see text] 3.5 (stat.) [Formula: see text] 5.7 (syst.) fb in the dilepton channel ([Formula: see text], [Formula: see text], and ee) using a method based on tight selection criteria, and 13.5 [Formula: see text] 3.3 (stat.) [Formula: see text] 3.6 (syst.) fb using a looser selection that allows the background normalisation to be extracted from data. The latter method also measures a value of 1.30 [Formula: see text] 0.33 (stat.) [Formula: see text] 0.28 (syst.)% for the ratio of [Formula: see text] production with two additional b-jets to [Formula: see text] production with any two additional jets. All measurements are in good agreement with recent theory predictions.
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  • Aad, G, et al. (författare)
  • Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at [Formula: see text] and 8 TeV in the ATLAS experiment.
  • 2016
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 76
  • Tidskriftsartikel (refereegranskat)abstract
    • Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the [Formula: see text] and [Formula: see text] decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 [Formula: see text] at [Formula: see text] TeV and 20.3 [Formula: see text] at [Formula: see text] TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is [Formula: see text]. The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered.
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  • Aad, G, et al. (författare)
  • Observation and measurements of the production of prompt and non-prompt [Formula: see text] mesons in association with a [Formula: see text] boson in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.
  • 2015
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The production of a [Formula: see text] boson in association with a [Formula: see text] meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using [Formula: see text] of data collected with the ATLAS experiment at the LHC in [Formula: see text] collisions at [Formula: see text], the first measurement of associated [Formula: see text] production is presented for both prompt and non-prompt [Formula: see text] production, with both signatures having a significance in excess of [Formula: see text]. The inclusive production cross-sections for [Formula: see text] boson production (analysed in [Formula: see text] or [Formula: see text] decay modes) in association with prompt and non-prompt [Formula: see text] are measured relative to the inclusive production rate of [Formula: see text] bosons in the same fiducial volume to be [Formula: see text] and [Formula: see text] respectively. Normalised differential production cross-section ratios are also determined as a function of the [Formula: see text] transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of [Formula: see text] at [Formula: see text] confidence level is placed on the effective cross-section regulating double parton interactions.
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