| 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. |
- Falster, Daniel, et al.
(författare)
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AusTraits, a curated plant trait database for the Australian flora
- 2021
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Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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| 3. |
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| 4. |
- Bateman, Randall J, et al.
(författare)
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Gantenerumab: an anti-amyloid monoclonal antibody with potential disease-modifying effects in early Alzheimer's disease.
- 2022
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal antibody as the first potential disease-modifying therapy for AD, signaled the value of more than 20 years of drug development, adding to the available therapies the first nominal success since cholinesterase inhibitors and memantine were approved. BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. Key learnings from the field were incorporated into the gantenerumab phase 3 program, including confirmed amyloid positivity as an entry criterion, an enriched clinical trial population to ensure measurable clinical decline, data-driven exposure-response models to inform a safe and efficacious dosing regimen, and the use of several blood-based biomarkers. Subcutaneous formulation for more pragmatic implementation was prioritized as a key feature from the beginning of the gantenerumab development program.The results from the gantenerumab phase 3 programs are expected by the end of 2022 and will add critical information to the collective knowledge on the search for effective AD treatments.
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| 5. |
- Bateman, Randall J., et al.
(författare)
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Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease
- 2023
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 389:20, s. 1862-1876
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease. Methods: We conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116. Results: A total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval [CI], -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aβ42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%. Conclusions: Among persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline.
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| 6. |
- Della Bruna, Lorenza, et al.
(författare)
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Studying the ISM at ∼10 pc scale in NGC 7793 with MUSEII : Constraints on the oxygen abundance and ionising radiation escape (Corrigendum)
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 663
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Tidskriftsartikel (refereegranskat)abstract
- Table 3 in the original paper reports inaccurate values of Q0exp;YSC and Q0obs(and hence of the related quantities Qexp;tot, Qexptot=Qobs, and fesc). The error in Q0exp;YSC results from a mistake in the sampling of the cluster probability distribution functions (PDFs), whereas Q0obswas mistakenly computed from non-dereddened values of L(Hα). In Table 1 we provide a revised version of the original Table 3, and in Figs. 1 and 2 we show revised versions of the original Figs. 10 and 11. The revised values do not change any of the conclusions stated in the original paper. In the following we provide revised text for the affected sections. (Figure Presented).
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| 7. |
- Della Bruna, Lorenza, et al.
(författare)
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Studying the ISM at similar to 10 pc scale in NGC 7793 with MUSE : II. Constraints on the oxygen abundance and ionising radiation escape
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 650
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Tidskriftsartikel (refereegranskat)abstract
- Context. Feedback from massive stars a ffects the interstellar medium (ISM) from the immediate surroundings of the stars (parsec scales) to galactic (kiloparsec) scales. High-spatial resolution studies of H ii regions are critical to investigate how this mechanism operates.Aims. We study the ionised ISM in NGC7793 with the MUSE instrument at ESO Very Large Telescope (VLT), over a field of view (FoV) of similar to 2 kpc2 and at a spatial resolution of similar to 10 pc. The aim is to link the physical conditions of the ionised gas (reddening, ionisation status, abundance measurements) within the spatially resolved H ii regions to the properties of the stellar populations producing Lyman continuum photons.Methods. The analysis of the MUSE dataset, which provides a map of the ionised gas and a census of Wolf Rayet stars, is complemented with a sample of young star clusters (YSCs) and O star candidates observed with the Hubble Space Telescope (HST) and of giant molecular clouds traced in CO(2-1) emission with the Atacama Large Millimeter /submillimeter Array (ALMA). We estimated the oxygen abundance using a temperature-independent strong-line method. We determined the observed total amount of ionising photons ( Q(H0)) from the extinction corrected H ff luminosity. This estimate was then compared to the expected Q(H0) obtained by summing the contributions of YSCs and massive stars. The ratio of the two values gives an estimate for the escape fraction ( fesc) of photons in the region of interest. We used the [S ii] /[O iii] ratio as a proxy for the optical depth of the gas and classified H ii regions into ionisation bounded, or as featuring channels of optically thin gas. We compared the resulting ionisation structure with the computed fesc. We also investigated the dependence of fesc on the age spanned by the stellar population in each region.Results. We find a median oxygen abundance of 12 + log (O =H) similar to 8 :37, with a scatter of 0.25 dex, which is in agreement with previous estimates for our target. We furthermore observe that the abundance map of H ii regions is rich in substructures, surrounding clusters and massive stars, although clear degeneracies with photoionisation are also observed. From the population synthesis analysis, we find that YSCs located in H ii regions have a higher probability of being younger and less massive as well as of emitting a higher number of ionising photons than clusters in the rest of the field. Overall, we find fesc;H ii = 0:67+0:08 0:12 for the population of H ii regions. We also conclude that the sources of ionisation observed within the FoV are more than su fficient to explain the amount of di ffuse ionised gas (DIG) observed in this region of the galaxy. We do not observe a systematic trend between the visual appearance of H ii regions and fesc, pointing to the e ffect of 3D geometry in the small sample probed.
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| 8. |
- Docherty, Anna R, et al.
(författare)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Tidskriftsartikel (refereegranskat)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 9. |
- Fatimah, Yuti A., et al.
(författare)
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Multi-level actor-network : Case of Peatland programs in a Riau Village, Indonesia (1974–2020)
- 2023
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Ingår i: Geoforum. - : Elsevier. - 0016-7185 .- 1872-9398. ; 145
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Tidskriftsartikel (refereegranskat)abstract
- This paper studies the survivability of peatland-related programs in Indonesia. Despite an increase in the global and national programs for peatland restoration, many of these programs fail to survive in the long-term. To understand this low survivability, this paper examines how peatland-related programs re-arrange the relationship between the local community and peatland across time and how the new actor-network contributes to the survivability of peatland programs. We develop a multi-level actor-network framework that combines the multi-level perspective from transition studies to capture the stability of actors’ relationships and power from actor-network theory to investigate how activities mobilise human and non-human actors to comply with a specific program. Our research shows that non-human actors such as peat, paddy, Acacia, and fire shape peatland-related programs by resisting non-suitable crops, by re-shaping the program, by mobilizing human actors, and by creating pressure to the existing regime. We highlight that the survivability of peatland restoration programs is strongly influenced by how they are adjusted to the materiality of these non-human actors. Given the importance of peatland restoration programs, our study provides an approach in which human and non-human come together to generate plural voices to ensure the survival of peatland restoration programs.
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| 10. |
- Finn, Molly K., et al.
(författare)
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ALMA-LEGUS. I. The Influence of Galaxy Morphology on Molecular Cloud Properties
- 2024
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 964:1
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Tidskriftsartikel (refereegranskat)abstract
- We present a comparative study of the molecular gas in two galaxies from the Legacy ExtraGalactic UV Survey (LEGUS) sample: barred spiral NGC 1313 and flocculent spiral NGC 7793. These two galaxies have similar masses, metallicities, and star formation rates, but NGC 1313 is forming significantly more massive star clusters than NGC 7793, especially young massive clusters (<10 Myr, >104M⊙). Using Atacama Large Millimeter/submillimeter Array (ALMA) CO(2–1) observations of the two galaxies with the same sensitivity and resolution (13 pc), we directly compare the molecular gas in these two similar galaxies to determine the physical conditions responsible for their large disparity in cluster formation. By fitting size–line width relations for the clouds in each galaxy, we find that NGC 1313 has a higher intercept than NGC 7793, implying that its clouds have higher kinetic energies at a given size scale. NGC 1313 also has more clouds near virial equilibrium than NGC 7793, which may be connected to its higher rate of massive cluster formation. However, these virially bound clouds do not show a stronger correlation with young clusters than with the general cloud population. We find surprisingly small differences between the distributions of molecular cloud populations in the two galaxies, though the largest of those differences is that NGC 1313 has higher surface densities and lower freefall times.
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