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| 2. |
- Nelson, G., et al.
(författare)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 4. |
- Lacour, S., et al.
(författare)
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The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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| 6. |
- Bjarnadottir, M, et al.
(författare)
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Intracellular accumulation of the amyloidogenic L68Q variant of cystatin C in NIH/3T3 cells
- 1998
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Ingår i: Molecular Pathology. - 1366-8714. ; 51:6, s. 317-326
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the cellular transport of L68Q cystatin C, the cystatin variant causing amyloidosis and brain haemorrhage in patients suffering from hereditary cystatin C amyloid angiopathy (HCCAA). METHODS: Expression vectors for wild-type and L68Q cystatin C were constructed and used to transfect mouse NIH/3T3 cells. Stable cell clones were isolated after cotransfection with pSV2neo. Clones expressing human wild-type and L68Q cystatin C were compared with respect to secreted cystatin C by enzyme linked immunosorbent assay (ELISA), and for intracellular cystatin C by western blotting and immunofluorescence cytochemistry. Colocalisation studies in cells were performed by double staining with antibodies against human cystatin C and marker proteins for lysosomes, the Golgi apparatus, or the endoplasmic reticulum, and evaluated by confocal microscopy. RESULTS: Concentrations of human cystatin C secreted from transfected NIH/3T3 cells were similar to those secreted from human cells in culture. In general, clones expressing the gene encoding L68Q cystatin C secreted slightly lower amounts of the protein than clones expressing wild-type human cystatin C. Both immunofluorescence cytochemistry and western blotting experiments showed an increased accumulation of cystatin C in cells expressing the gene encoding L68Q cystatin C compared with cells expressing the gene for the wild-type protein. The intracellularly accumulating L68Q cystatin C was insoluble and located mainly in the endoplasmic reticulum. CONCLUSIONS: The cellular transport of human cystatin C is impeded by the pathogenic amino acid substitution Leu68-- >Gln. The resulting intracellular accumulation and increased localised concentration of L68Q cystatin C might be an important event in the molecular pathophysiology of amyloid formation and brain haemorrhage in patients with HCCAA.
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| 7. |
- Bonnefoy, M., et al.
(författare)
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The GJ 504 system revisited Combining interferometric, radial velocity, and high contrast imaging data
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
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Tidskriftsartikel (refereegranskat)abstract
- Context. The G-type star GJ504A is known to host a 3-35 M-Jup companion whose temperature, mass, and projected separation all contribute to making it a test case for planet formation theories and atmospheric models of giant planets and light brown dwarfs. Aims. We aim at revisiting the system age, architecture, and companion physical and chemical properties using new complementary interferometric, radial-velocity, and high-contrast imaging data. Methods. We used the CHARA interferometer to measure GJ504A's angular diameter and obtained an estimation of its radius in combination with the HIPPARCOS parallax. The radius was compared to evolutionary tracks to infer a new independent age range for the system. We collected dual imaging data with IRDIS on VLT/SPHERE to sample the near-infrared (1.02-2.25 mu m) spectral energy distribution (SED) of the companion. The SED was compared to five independent grids of atmospheric models (petitCODE, Exo-REM, BT-SETTL, Morley et al., and ATMO) to infer the atmospheric parameters of GJ 504b and evaluate model-to-model systematic errors. In addition, we used a specific model grid exploring the effect of different C/O ratios. Contrast limits from 2011 to 2017 were combined with radial velocity data of the host star through the MESS2 tool to define upper limits on the mass of additional companions in the system from 0.01 to 100 au. We used an MCMC fitting tool to constrain the companion's orbital parameters based on the measured astrometry, and dedicated formation models to investigate its origin. Results. We report a radius of 1.35 +/- 0.04 R-circle dot for GJ504A. The radius yields isochronal ages of 21 +/- 2 Myr or 4.0 +/- 1.8 Gyr for the system and line-of-sight stellar rotation axis inclination of 162.4(-4.3)(+3.8) degrees or 18.6(-3.8)(+4.3) degrees. We re-detect the companion in the Y2, Y3, J3, H2, and K1 dual-band images. The complete 1-4 mu m SED shape of GJ504b is best reproduced by T8-T9.5 objects with intermediate ages (<= 1.5Gyr), and/or unusual dusty atmospheres and/or super-solar metallicities. All atmospheric models yield T-eff = 550 +/- 50 K for GJ504b and point toward a low surface gravity (3.5-4.0 dex). The accuracy on the metallicity value is limited by model-to-model systematics; it is not degenerate with the C/O ratio. We derive log L/L-circle dot = 6.15 +/- 0.15 dex for the companion from the empirical analysis and spectral synthesis. The luminosity and T-eff yield masses of M = 1.3(-0.3)(+0.6) M-Jup and M = 23(-9)(+10) M-Jup for the young and old age ranges, respectively. The semi-major axis (sma) is above 27.8 au and the eccentricity is lower than 0.55. The posterior on GJ 504b's orbital inclination suggests a misalignment with the rotation axis of GJ 504A. We exclude additional objects (90% prob.) more massive than 2.5 and 30 M-Jup with semi-major axes in the range 0.01-80 au for the young and old isochronal ages, respectively. Conclusions. The mass and semi-major axis of GJ 504b are marginally compatible with a formation by disk-instability if the system is 4 Gyr old. The companion is in the envelope of the population of planets synthesized with our core-accretion model. Additional deep imaging and spectroscopic data with SPHERE and JWST should help to confirm the possible spin-orbit misalignment and refine the estimates on the companion temperature, luminosity, and atmospheric composition.
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| 8. |
- Chauvin, G., et al.
(författare)
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Discovery of a warm, dusty giant planet around HIP 65426
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The SHINE program is a high-contrast near-infrared survey of 600 young, nearby stars aimed at searching for and characterizing new planetary systems using VLT/SPHERE's unprecedented high-contrast and high-angular-resolution imaging capabilities. It is also intended to place statistical constraints on the rate, mass and orbital distributions of the giant planet population at large orbits as a function of the stellar host mass and age to test planet-formation theories.Methods. We used the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-contrast coronagraphic differential near-infrared images and spectra of the young A2 star HIP 65426. It is a member of the similar to 17 Myr old Lower Centaurus-Crux association. Results. At a separation of 830 mas (92 au projected) from the star, we detect a faint red companion. Multi-epoch observations confirm that it shares common proper motion with HIP 65426. Spectro-photometric measurements extracted with IFS and IRDIS between 0.95 and 2.2 mu m indicate a warm, dusty atmosphere characteristic of young low-surface-gravity L5-L7 dwarfs. Hot-start evolutionary models predict a luminosity consistent with a 6-12 M-Jup, T-eff = 1300-1600K and R = 1.5 +/- 0.1 R-Jup giant planet. Finally, the comparison with Exo-REM and PHOENIX BT-Settl synthetic atmosphere models gives consistent effective temperatures but with slightly higher surface gravity solutions of log(g) = 4.0-5.0 with smaller radii (1.0-1.3 R-Jup).Conclusions. Given its physical and spectral properties, HIP 65426 b occupies a rather unique placement in terms of age, mass, and spectral-type among the currently known imaged planets. It represents a particularly interesting case to study the presence of clouds as a function of particle size, composition, and location in the atmosphere, to search for signatures of non-equilibrium chemistry, and finally to test the theory of planet formation and evolution.
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| 9. |
- Cheetham, A., et al.
(författare)
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Discovery of a brown dwarf companion to the star HIP 64892
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a bright, brown dwarf companion to the star HIP 64892, imaged with VLT/SPHERE during the SHINE exoplanet survey. The host is a B9.5V member of the Lower-Centaurus-Crux subgroup of the Scorpius Centaurus OB association. The measured angular separation of the companion (1.2705 +/- 0.0023) corresponds to a projected distance of 159 +/- 12AU. We observed the target with the dual-band imaging and long-slit spectroscopy modes of the IRDIS imager to obtain its spectral energy distribution (SED) and astrometry. In addition, we reprocessed archival NACO L-band data, from which we also recover the companion. Its SED is consistent with a young (<30 Myr), low surface gravity object with a spectral type of M9 gamma +/- 1. From comparison with the BT-Settl atmospheric models we estimate an effective temperature of T-eff = 2600 +/- 100 K, and comparison of the companion photometry to the COND evolutionary models yields a mass of similar to 29-37 M-J at the estimated age of 16(-7)(+15) Myr for the system. The star HIP 64892 is a rare example of an extreme-mass ratio system (q similar to 0.01) and will be useful for testing models relating to the formation and evolution of such low-mass objects.
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| 10. |
- Heffeter, P., et al.
(författare)
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Ribonucleotide Reductase as One Important Target of [Tris(1,10- phenanthroline)lanthanum(III)] Trithiocyanate (KP772)
- 2009
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Ingår i: Current Cancer Drug Targets. - : Bentham Science Publishers Ltd.. - 1568-0096 .- 1873-5576. ; 9:5, s. 595-607
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Tidskriftsartikel (refereegranskat)abstract
- KP772 is a new lanthanum complex containing three 1,10-phenathroline molecules. Recently, we have demonstrated that the promising in vitro and in vivo anticancer properties of KP772 are based on p53-independent G(0)G(1) arrest and apoptosis induction. A National Cancer Institute (NCI) screen revealed significant correlation of KP772 activity with that of the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU). Consequently, this study aimed to investigate whether KP772 targets DNA synthesis in tumor cells by RR inhibition. Indeed, KP772 treatment led to significant reduction of cytidine incorporation paralleled by a decrease of deoxynucleoside triphosphate (dNTP) pools. This strongly indicates disruption of RR activity. Moreover, KP772 protected against oxidative stress, suggesting that this drug might interfere with RR by interaction with the tyrosyl radical in subunit R2. Additionally, several observations (e.g. increase of transferrin receptor expression and protective effect of iron preloading) indicate that KP772 interferes with cellular iron homeostasis. Accordingly, co-incubation of Fe(II) with KP772 led to generation of a coloured iron complex (Fe-KP772) in cell free systems. In electron paramagnetic resonance (EPR) measurements of mouse R2 subunits, KP772 disrupted the tyrosyl radical while Fe-KP772 had no significant effects. Moreover, coincubation of KP772 with iron-loaded R2 led to formation of Fe-KP772 suggesting chelation of RR-bound Fe(II). Summarizing, our data prove that KP772 inhibits RR by targeting the iron centre of the R2 subunit. As also Fe-KP772 as well as free lanthanum exert significant -though less pronounced- cytotoxic/static activities, additional mechanisms are likely to synergise with RR inhibition in the promising anticancer activity of KP772.
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