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1.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • 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.
  • Abelev, Betty, et al. (author)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Journal article (peer-reviewed)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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3.
  • Abelev, Betty, et al. (author)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :11
  • Journal article (peer-reviewed)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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4.
  • Abelev, Betty, et al. (author)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • In: Journal of High Energy Physics. - 1029-8479. ; :7
  • Journal article (peer-reviewed)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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5.
  • De Petris, Luigi, et al. (author)
  • Diagnostic and prognostic role of plasma levels of two forms of cytokeratin 18 in patients with non-small-cell lung cancer
  • 2011
  • In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 47:1, s. 131-137
  • Journal article (peer-reviewed)abstract
    • PURPOSE:Cytokeratin 18 (CK18) can be used as a serum biomarker for carcinoma cell death, whereas caspase-cleaved (ccCK18) fragments reflect tumour apoptosis. We explored the potential diagnostic and prognostic role of circulating CK18 and ccCK18 in patients with non-small-cell lung cancer (NSCLC) in comparison with Cyfra 21.1, a fragment of cytokeratin 19.METHODS:Subject cohorts consisted of 200 healthy blood donors (HBD), 113 patients with benign lung diseases (BLD) and 179 NSCLC cases. Plasma levels of ccCK18, total CK18 and Cyfra 21.1 were determined with ELISA assays.RESULTS:Plasma levels of ccCK18 and total CK18 were higher in the NSCLC group compared to the HBD and BLD cohorts (p<0.0001). Using a cut-off of 104 U/L for ccCK18 and 302 U/L for total CK18 (95% specificity in the HBD group) the diagnostic accuracy of both CK18 forms to distinguish between NSCLC and BLD cases was 56%, whereas it was 94% for Cyfra 21.1. Multivariate survival analysis showed that total CK18 was a stronger prognostic factor than both ccCK18 and Cyfra 21.1 (HR 0.64 for low versus high total CK18 levels, 95% confidence interval (CI) 0.50-0.82; p=0.0004) in the entire NSCLC cohort and in 78 patients with locally advanced or metastatic disease treated with chemoradiotherapy or first-line chemotherapy (HR 0.70 95% CI 0.52-0.94; p=0.018).CONCLUSIONS:Cyfra 21.1 is a useful diagnostic biomarker for NSCLC. Total CK18 shows a promising potential as prognostic marker in NSCLC patients, independently of the therapeutical intervention. In contrast, ccCK18 was not of prognostic value in NSCLC, suggesting that tumour necrosis is of particular importance in this disease.
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6.
  • Fages, Anne, et al. (author)
  • Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort.
  • 2015
  • In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is incomplete etiologic understanding of the disease and little progress in identification of early risk biomarkers.
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9.
  • Hudson, Lawrence N, et al. (author)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Journal article (peer-reviewed)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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10.
  • Karlsson, Elin, et al. (author)
  • Disordered Regions Flanking the Binding Interface Modulate Affinity between CBP and NCOA
  • 2022
  • In: Journal of Molecular Biology. - : Elsevier. - 0022-2836 .- 1089-8638. ; 434:13
  • Journal article (peer-reviewed)abstract
    • Recognition motifs that mediate protein-protein interactions are usually embedded within longer intrinsically disordered regions. While binding interfaces involving the recognition motif in such interactions are well studied, less is known about the role of disordered regions flanking the motifs. The interaction between the transcriptional co-activators NCOA3 (ACTR) and CBP is mediated by coupled binding and folding of the two domains CID and NCBD. Here, we used circular dichroism and kinetics to directly quantify the contribution of the adjacent flanking regions of CID to its interaction with NCBD. Using N-and C terminal combinatorial variants we found that the flanking regions promote binding in an additive fashion while retaining a large degree of disorder in the complex. Experiments at different ionic strengths demonstrated that the increase in affinity is not mediated by electrostatic interactions from the flanking regions. Instead, site-directed mutagenesis and molecular dynamics simulations suggest that binding is promoted by short-lived non-specific hydrophobic contacts between the flanking regions and NCBD. Our findings are consistent with highly frustrated interactions outside of the canonical binding interface resulting in a slightly energetically favorable fuzzy binding. Modulation of affinity via flanking regions could represent a general mechanism for functional regulation by intrinsically disordered protein regions.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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12.
  • Witjes, J. Alfred, et al. (author)
  • EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
  • 2020
  • In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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13.
  • Zewinger, Stephen, et al. (author)
  • Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study
  • 2017
  • In: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:7, s. 534-543
  • Journal article (peer-reviewed)abstract
    • Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
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