| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Morris, Simon, et al.
(författare)
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The ELT-MOS (MOSAIC) : towards the construction phase
- 2018
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Ingår i: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY VII. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510619586 ; 10702
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Konferensbidrag (refereegranskat)abstract
- When combined with the huge collecting area of the ELT, MOSAIC will be the most effective and flexible Multi-Object Spectrograph (MOS) facility in the world, having both a high multiplex and a multi-Integral Field Unit (Multi-IFU) capability. It will be the fastest way to spectroscopically follow-up the faintest sources, probing the reionisation epoch, as well as evaluating the evolution of the dwarf mass function over most of the age of the Universe. MOSAIC will be world-leading in generating an inventory of both the dark matter (from realistic rotation curves with MOAO fed NIR IFUs) and the cool to warm-hot gas phases in z=3.5 galactic haloes (with visible wavelenth IFUs). Galactic archaeology and the first massive black holes are additional targets for which MOSAIC will also be revolutionary. MOAO and accurate sky subtraction with fibres have now been demonstrated on sky, removing all low Technical Readiness Level (TRL) items from the instrument. A prompt implementation of MOSAIC is feasible, and indeed could increase the robustness and reduce risk on the ELT, since it does not require diffraction limited adaptive optics performance. Science programmes and survey strategies are currently being investigated by the Consortium, which is also hoping to welcome a few new partners in the next two years.
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| 3. |
- Repsilber, Dirk, 1971-, et al.
(författare)
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Data rotation improves genomotyping efficiency
- 2005
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Ingår i: Biometrical Journal. - Berlin, Germany : Wiley. - 0323-3847 .- 1521-4036. ; 47:4, s. 585-598
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Tidskriftsartikel (refereegranskat)abstract
- Unsequenced bacterial strains can be characterized by comparing their genomic DNA to a sequenced reference genome of the same species. This comparative genomic approach, also called genomotyping, is leading to an increased understanding of bacterial evolution and pathogenesis. It is efficiently accomplished by comparative genomic hybridization on custom-designed cDNA microarrays. The microarray experiment results in fluorescence intensities for reference and sample genome for each gene. The logratio of these intensities is usually compared to a cut-off, classifying each gene of the sample genome as a candidate for an absent or present gene with respect to the reference genome. Reducing the usually high rate of false positives in the list of candidates for absent genes is decisive for both time and costs of the experiment. We propose a novel method to improve efficiency of genomotyping experiments in this sense, by rotating the normalized intensity data before setting up the list of candidate genes. We analyze simulated genomotyping data and also re-analyze an experimental data set for comparison and illustration. We approximately halve the proportion of false positives in the list of candidate absent genes for the example comparative genomic hybridization experiment as well as for the simulation experiments.
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| 4. |
- Dong, Shuo, et al.
(författare)
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Observation of ultrafast interfacial Meitner-Auger energy transfer in a Van der Waals heterostructure
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Atomically thin layered van der Waals heterostructures feature exotic and emergent optoelectronic properties. With growing interest in these novel quantum materials, the microscopic understanding of fundamental interfacial coupling mechanisms is of capital importance. Here, using multidimensional photoemission spectroscopy, we provide a layer- and momentum-resolved view on ultrafast interlayer electron and energy transfer in a monolayer-WSe2/graphene heterostructure. Depending on the nature of the optically prepared state, we find the different dominating transfer mechanisms: while electron injection from graphene to WSe2 is observed after photoexcitation of quasi-free hot carriers in the graphene layer, we establish an interfacial Meitner-Auger energy transfer process following the excitation of excitons in WSe2. By analysing the time-energy-momentum distributions of excited-state carriers with a rate-equation model, we distinguish these two types of interfacial dynamics and identify the ultrafast conversion of excitons in WSe2 to valence band transitions in graphene. Microscopic calculations find interfacial dipole-monopole coupling underlying the Meitner-Auger energy transfer to dominate over conventional Förster- and Dexter-type interactions, in agreement with the experimental observations. The energy transfer mechanism revealed here might enable new hot-carrier-based device concepts with van der Waals heterostructures.
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| 5. |
- Emanuelsson, Andreas, et al.
(författare)
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Accounting for overfishing in life cycle assessment: new impact categories for biotic resource use
- 2014
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Ingår i: International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 19:5, s. 1156-1168
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Tidskriftsartikel (refereegranskat)abstract
- Overfishing is a relevant issue to include in all life cycle assessments (LCAs) involving wild caught fish, as overfishing of fish stocks clearly targets the LCA safeguard objects of natural resources and natural ecosystems. Yet no robust method for assessing overfishing has been available. We propose lost potential yield (LPY) as a midpoint impact category to quantify overfishing, comparing the outcome of current with target fisheries management. This category primarily reflects the impact on biotic resource availability, but also serves as a proxy for ecosystem impacts within each stock. LPY represents average lost catches owing to ongoing overfishing, assessed by simplified biomass projections covering different fishing mortality scenarios. It is based on the maximum sustainable yield concept and complemented by two alternative methods, overfishing though fishing mortality (OF) and overfishedness of biomass (OB), that are less data-demanding. Characterization factors are provided for 31 European commercial fish stocks in 2010, representing 74 % of European and 7 % of global landings. However, large spatial and temporal variations were observed, requiring novel approaches for the LCA practitioner. The methodology is considered compliant with the International Reference Life Cycle Data System (ILCD) standard in most relevant aspects, although harmonization through normalization and endpoint characterization is only briefly discussed. Seafood LCAs including any of the three approaches can be a powerful communicative tool for the food industry, seafood certification programmes, and for fisheries management.
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| 6. |
- Jacobsen, Marc, et al.
(författare)
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Candidate biomarkers for discrimination between infection and disease caused by Mycobacterium tuberculosis
- 2007
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Ingår i: Journal of Molecular Medicine. - New York, USA : Springer. - 0946-2716 .- 1432-1440. ; 85:6, s. 613-21
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Tidskriftsartikel (refereegranskat)abstract
- Infection with Mycobacterium tuberculosis is controlled by an efficacious immune response in about 90% of infected individuals who do not develop disease. Although essential mediators of protection, e.g., interferon-gamma, have been identified, these factors are insufficient to predict the outcome of M. tuberculosis infection. As a first step to determine additional biomarkers, we compared gene expression profiles of peripheral blood mononuclear cells from tuberculosis patients and M. tuberculosis-infected healthy donors by microarray analysis. Differentially expressed candidate genes were predominantly derived from monocytes and comprised molecules involved in the antimicrobial defense, inflammation, chemotaxis, and intracellular trafficking. We verified differential expression for alpha-defensin 1, alpha-defensin 4, lactoferrin, Fcgamma receptor 1A (cluster of differentiation 64 [CD64]), bactericidal permeability-increasing protein, and formyl peptide receptor 1 by quantitative polymerase chain reaction analysis. Moreover, we identified increased protein expression of CD64 on monocytes from tuberculosis patients. Candidate biomarkers were then assessed for optimal study group discrimination. Using a linear discriminant analysis, a minimal group of genes comprising lactoferrin, CD64, and the Ras-associated GTPase 33A was sufficient for classification of (1) tuberculosis patients, (2) M. tuberculosis-infected healthy donors, and (3) noninfected healthy donors.
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| 7. |
- Jacobsen, Marc, et al.
(författare)
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Deconfounding microarray analysis : independent measurements of cell type proportions used in a regression model to resolve tissue heterogeneity bias
- 2006
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Ingår i: Methods of Information in Medicine. - Stuttgart, Germany : Schattauer Gmbh. - 0026-1270 .- 2511-705X. ; 45:5, s. 557-63
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Microarray analysis requires standardized specimens and evaluation procedures to achieve acceptable results. A major limitation of this method is caused by heterogeneity in the cellular composition of tissue specimens, which frequently confounds data analysis. We introduce a linear model to deconfound gene expression data from tissue heterogeneity for genes exclusively expressed by a single cell type.Methods: Gene expression data are deconfounded from tissue heterogeneity effects by analyzing them using an appropriate linear regression model. In our illustrating data set tissue heterogeneity is being measured using flow cytometry. Gene expression data are determined in parallel by real time quantitative polymerase chain reaction (qPCR) and microarray analyses. Verification of deconfounding is enabled using protein quantification for the respective marker genes.Results: For our illustrating dataset, quantification of cell type proportions for peripheral blood mononuclear cells (PBMC) from tuberculosis patients and controls revealed differences in B cell and monocyte proportions between both study groups, and thus heterogeneity for the tissue under investigation. Gene expression analyses reflected these differences in celltype distribution. Fitting an appropriate linear model allowed us to deconfound measured transcriptome levels from tissue heterogeneity effects. In the case of monocytes, additional differential expression on the single cell level could be proposed. Protein quantification verified these deconfounded results.Conclusions: Deconfounding of transcriptome analyses for cellular heterogeneity greatly improves interpretability, and hence the validity of transcriptome profiling results.
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| 8. |
- Jacobsen, Marc, et al.
(författare)
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Ras-associated small GTPase 33A, a novel T cell factor, is down-regulated in patients with tuberculosis
- 2005
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Ingår i: Journal of Infectious Diseases. - Chicago, USA : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 192:7, s. 1211-8
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Tidskriftsartikel (refereegranskat)abstract
- Ras-associated small GTPases (Rabs) are specific regulators of intracellular vesicle trafficking. Interference with host cell vesicular transport is a hallmark of many intracellular pathogens, including the notable example Mycobacterium tuberculosis. We performed, by quantitative polymerase chain reaction, gene-expression analyses for selected Rab molecules in peripheral-blood mononuclear cells from patients with tuberculosis (TB) and healthy control subjects, to identify candidate genes that are critically involved in the host immune response. Comparison revealed significant differences in the expression of genes for Rab13, Rab24, and Rab33A. Rab33A gene expression was down-regulated in patients with TB and was predominantly expressed in CD8+ T cells. We excluded possible influences of differences in T cell percentages between the 2 study groups, demonstrating that Rab33A gene expression changes on the single-cell level. In vitro, Rab33A RNA expression was induced in T cells on activation and by dendritic cells infected with M. tuberculosis. Our findings identify Rab33A as a T cell regulatory molecule in TB and suggest its involvement in disease processes.
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| 9. |
- Laraia, Luca, et al.
(författare)
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The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis
- 2019
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 15:7, s. 710-720
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis. Using target-agnostic, high-content, image-based identification of indicative phenotypic changes induced by small molecules, we have identified autogramins as a new class of autophagy inhibitor. Autogramins selectively target the recently discovered cholesterol transfer protein GRAM domain-containing protein 1A (GRAMD1A, which had not previously been implicated in autophagy), and directly compete with cholesterol binding to the GRAMD1A StART domain. GRAMD1A accumulates at sites of autophagosome initiation, affects cholesterol distribution in response to starvation and is required for autophagosome biogenesis. These findings identify a new biological function of GRAMD1A and a new role for cholesterol in autophagy.
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| 10. |
- Lüscher, Bernhard, et al.
(författare)
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ADP-ribosyltransferases, an update on function and nomenclature
- 2022
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Ingår i: The FEBS Journal. - : John Wiley & Sons. - 1742-464X .- 1742-4658. ; 289:23, s. 7399-7410
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Tidskriftsartikel (refereegranskat)abstract
- ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD+ onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases. Importantly, inhibitors of ARTs are approved or are being developed for clinical use. Moreover, ADP-ribosylhydrolases are being assessed as therapeutic targets, foremost as antiviral drugs and for oncological indications. Due to the development of novel reagents and major technological advances that allow the study of ADP-ribosylation in unprecedented detail, an increasing number of cellular processes and pathways are being identified that are regulated by ADP-ribosylation. In addition, characterization of biochemical and structural aspects of the ARTs and their catalytic activities have expanded our understanding of this protein family. This increased knowledge requires that a common nomenclature be used to describe the relevant enzymes. Therefore, in this viewpoint, we propose an updated and broadly supported nomenclature for mammalian ARTs that will facilitate future discussions when addressing the biochemistry and biology of ADP-ribosylation. This is combined with a brief description of the main functions of mammalian ARTs to illustrate the increasing diversity of mono- and poly-ADP-ribose mediated cellular processes.
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