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Sökning: WFRF:(Koch Eric)

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2.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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3.
  • 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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  • Babbin, Brian A., et al. (författare)
  • Annexin A1 regulates intestinal mucosal injury, inflammation, and repair
  • 2008
  • Ingår i: Journal of Immunology. - Bethesda, United States : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 181:7, s. 5035-5044
  • Tidskriftsartikel (refereegranskat)abstract
    • During mucosal inflammation, a complex array of proinflammatory and protective mechanisms regulates inflammation and severity of injury. Secretion of anti-inflammatory mediators is a mechanism that is critical in controlling inflammatory responses and promoting epithelial restitution and barrier recovery. AnxA1 is a potent anti-inflammatory protein that has been implicated to play a critical immune regulatory role in models of inflammation. Although AnxA1 has been shown to be secreted in intestinal mucosal tissues during inflammation, its potential role in modulating the injury/inflammatory response is not understood. In this study, we demonstrate that AnxA1-deficient animals exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis with greater clinical morbidity and histopathologic mucosal injury. Furthermore, impaired recovery following withdrawal of DSS administration was observed in AnxA1 (-/-) animals compared with wild-type (WT) control mice that was independent of inflammatory cell infiltration. Since AnxA1 exerts its anti-inflammatory properties through stimulation of ALX/FPRL-1, we explored the role of this receptor-ligand interaction in regulating DSS-induced colitis. Interestingly, treatment with an ALX/FPRL-1 agonist, 15-epi-lipoxin A4 reversed the enhanced sensitivity of AnxA1 (-/-) mice to DSS colitis. In contrast, 15-epi-lipoxin A4 did not significantly improve the severity of disease in WT animals. Additionally, differential expression of ALX/FPLR-1 in control and DSS-treated WT and AnxA1-deficient animals suggested a potential role for AnxA1 in regulating ALX/FPRL-1 expression under pathophysiological conditions. Together, these results support a role of endogenous AnxA1 in the protective and reparative properties of the intestinal mucosal epithelium.
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6.
  • Henshaw, Jonathan D., et al. (författare)
  • Ubiquitous velocity fluctuations throughout the molecular interstellar medium
  • 2020
  • Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 4:11, s. 1064-1071
  • Tidskriftsartikel (refereegranskat)abstract
    • The density structure of the interstellar medium determines where stars form and release energy, momentum and heavy elements, driving galaxy evolution1–4. Density variations are seeded and amplified by gas motion, but the exact nature of this motion is unknown across spatial scales and galactic environments5. Although dense star-forming gas probably emerges from a combination of instabilities6,7, convergent flows8 and turbulence9, establishing the precise origin is challenging because it requires gas motion to be quantified over many orders of magnitude in spatial scale. Here we measure10–12 the motion of molecular gas in the Milky Way and in nearby galaxy NGC 4321, assembling observations that span a spatial dynamic range 10−1–103 pc. We detect ubiquitous velocity fluctuations across all spatial scales and galactic environments. Statistical analysis of these fluctuations indicates how star-forming gas is assembled. We discover oscillatory gas flows with wavelengths ranging from 0.3–400 pc. These flows are coupled to regularly spaced density enhancements that probably form via gravitational instabilities13,14. We also identify stochastic and scale-free velocity and density fluctuations, consistent with the structure generated in turbulent flows9. Our results demonstrate that the structure of the interstellar medium cannot be considered in isolation. Instead, its formation and evolution are controlled by nested, interdependent flows of matter covering many orders of magnitude in spatial scale.
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7.
  • Koch, Daniel, et al. (författare)
  • 2,2 '-Biindolyl Reactions with Aldehydes
  • 2016
  • Ingår i: European Journal of Organic Chemistry. - : Wiley-VCH Verlag. - 1434-193X .- 1099-0690. ; :7, s. 1389-1396
  • Tidskriftsartikel (refereegranskat)abstract
    • 2,2'-Biindolyl has been condensed with aromatic and aliphatic aldehydes and products featuring 10-membered rings have been obtained. Thus, benzaldehyde gave compound 24a as the primary product, which readily underwent transannular oxidative coupling to 25a. The structures of both compounds were confirmed by X-ray crystallography. The product from 2,2'-biindolyl and formaldehyde under strongly acidic conditions was slightly different leading to compound 11, whose structure also was confirmed by X-ray crystallography. In this case, two molecules of 2,2'-biindolyl reacted with six molecules of formaldehyde.
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8.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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9.
  • Thilker, David A., et al. (författare)
  • PHANGS–JWST First Results : The Dust Filament Network of NGC 628 and Its Relation to Star Formation Activity
  • 2023
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:2
  • Tidskriftsartikel (refereegranskat)abstract
    • PHANGS–JWST mid-infrared (MIR) imaging of nearby spiral galaxies has revealed ubiquitous filaments of dust emission in intricate detail. We present a pilot study to systematically map the dust filament network (DFN) at multiple scales between 25 and 400 pc in NGC 628. MIRI images at 7.7, 10, 11.3, and 21 μm of NGC 628 are used to generate maps of the filaments in emission, while PHANGS–HST B-band imaging yields maps of dust attenuation features. We quantify the correspondence between filaments traced by MIR thermal continuum/polycyclic aromatic hydrocarbon (PAH) emission and filaments detected via extinction/scattering of visible light; the fraction of MIR flux contained in the DFN; and the fraction of H ii regions, young star clusters, and associations within the DFN. We examine the dependence of these quantities on the physical scale at which the DFN is extracted. With our highest-resolution DFN maps (25 pc filament width), we find that filaments in emission and attenuation are cospatial in 40% of sight lines, often exhibiting detailed morphological agreement; that ∼30% of the MIR flux is associated with the DFN; and that 75%–80% of the star formation in H ii regions and 60% of the mass in star clusters younger than 5 Myr are contained within the DFN. However, the DFN at this scale is anticorrelated with looser associations of stars younger than 5 Myr identified using PHANGS–HST near-UV imaging. We discuss the impact of these findings on studies of star formation and the interstellar medium, and the broad range of new investigations enabled by multiscale maps of the DFN.
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  • Albrecht, Stefano V., et al. (författare)
  • Reports on the 2015 AAAI Workshop Series
  • 2015
  • Ingår i: The AI Magazine. - : Wiley. - 0738-4602 .- 2371-9621. ; 36:2, s. 90-101
  • Tidskriftsartikel (refereegranskat)abstract
    • AAAI's 2015 Workshop Program was held Sunday and Monday, January 25-26, 2015, at the Hyatt Regency Austin Hotel in Austin, Texas, USA. The AAAI-15 workshop program included 16 workshops covering a wide range of topics in artificial intelligence. Most workshops were held on a single day. The titles of the workshops included Algorithm Configuration; Artificial Intelligence and Ethics; Artificial Intelligence Applied to Assistive Technologies and Smart Environments; Artificial Intelligence for Cities; Artificial Intelligence for Transportation: Advice, Inter-activity, and Actor Modeling; Beyond the Turing Test; Computational Sustainability; Computer Poker and Imperfect Information; Incentive and Trust in E-Communities; Knowledge, Skill, and Behavior Transfer in Autonomous Robots; Learning for General Competency in Video Games; Multiagent Interaction without Prior Coordination; Planning, Search, and Optimization; Scholarly Big Data: AI Perspectives, Challenges, and Ideas; Trajectory-Based Behaviour Analytics; and World Wide Web and Public Health Intelligence.
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12.
  • Bertoft, Eric, et al. (författare)
  • Building block organisation of clusters in amylopectin from different structural types
  • 2012
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 50, s. 1212-1223
  • Tidskriftsartikel (refereegranskat)abstract
    • Clusters of chains consisting of tightly branched units of building blocks were isolated from 10 amylopectin samples possessing the 4 types of amylopectin with different internal unit chain profiles previously described. It was shown that clusters in types 1 and 2 amylopectins are larger than in types 3 and 4, but the average cluster size did not correspond to the ratio of short to long chains of the amylopectins. The size-distribution of the building blocks, having one or several branches, possessed generally only small differences between samples. However, the length of the interblock segments followed the type of amylopectin structure, so that type 1 amylopectins had shortest and type 4 the longest segments. The chains in the clusters were divided into characteristic groups probably being involved in the interconnection of two, three, and four - or more - building blocks. Long chains were typically found in high amounts in clusters from type 4 amylopectins, however, all cluster samples contained long chains. The results are discussed in terms of the building block structure of amylopectin, in which the blocks together with the interblock segments participate in a branched backbone building up the amorphous lamellae inside growth rings of the starch granules. In such a model, amylopectins with proportionally less long chains (types 1 and 2) possess a more extensively branched backbone compared to those with more long chains (types 3 and 4). (C) 2012 Elsevier B.V. All rights reserved.
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13.
  • Bertoft, Eric, et al. (författare)
  • The building block structure of barley amylopectin
  • 2011
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 49, s. 900-909
  • Tidskriftsartikel (refereegranskat)
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15.
  • Brandstedt, Eric, et al. (författare)
  • The Concept of Sustainable Welfare
  • 2016
  • Ingår i: Sustainability and the Political Economy of Welfare. - 9781138925281 - 9781315683850 ; 42, s. 15-28
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)
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20.
  • Crosby, Jacy, et al. (författare)
  • Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
  • 2014
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 371:1, s. 22-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)
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21.
  • de Jong, Roelof S., et al. (författare)
  • 4MOST-4-metre Multi-Object Spectroscopic Telescope
  • 2014
  • Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147
  • Konferensbidrag (refereegranskat)abstract
    • 4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with similar to 2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; similar to 1600 fibres go to two spectrographs with resolution R> 5000 (lambda similar to 390-930 nm) and similar to 800 fibres to a spectrograph with R> 18,000 (lambda similar to 392-437 nm & 515-572 nm & 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].
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22.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • 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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23.
  • Hendriks, Kasper P., et al. (författare)
  • Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
  • 2023
  • Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
  • Tidskriftsartikel (refereegranskat)abstract
    • The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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24.
  • Hinton, Jennifer B., 1982- (författare)
  • Relationship-to-Profit : A Theory of Business, Markets, and Profit for Social Ecological Economics
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • How does the relationship between business and profit affect social and ecological sustainability? Many sustainability scholars have identified competition for profit in the market as a key driver of social exploitation and environmental destruction. Yet, studies rarely question whether businesses and markets have to be profit-seeking. The widespread existence of not-for-profit forms of business, which approach profit as a means to achieving social benefit, suggests that there are other ways of organizing business and markets that might be more sustainable.In this thesis, I use a critical institutional economics lens and systems thinking to synthesize existing theory and knowledge about how business, markets, and profit affect sustainability outcomes, in order to explain how alternative approaches to these institutions might produce different outcomes. The result is a new theory about how relationship-to-profit (the legal difference between for-profit and not-for-profit forms of business) plays a key role in the sustainability of an economy, due to the ways in which it guides and constrains actors’ behavior, and drives larger market dynamics.In Paper 1, I develop a conceptual framework for understanding the tradeoffs and synergies between profit and social-ecological sustainability. I show how profit-seeking strategies can be examined to assess whether they derive profit from: efficiency gains; willing and informed contributions from social stakeholders; or exploitation of social or ecological stakeholders. These bounded sources of profit imply limits to profit. Therefore, in order for businesses and markets to be sustainable, they should treat profit as a means rather than an end in itself. In Paper 2, I explain that whether profit is treated as a means or an end manifests through both voluntary objectives (i.e., if a business explicitly pursues profit as a goal) and financial rights (i.e., the right or obligation to distribute profit to private owners). Some forms of business encourage profit-as-an-end more than others. In Paper 3, I outline ideal types of for-profit and not-for-profit economies, and describe the expected dynamics of these systems based on the regulative aspects of relationship-to-profit. The legal purpose, ownership (i.e., private financial rights), and corresponding investment structures of for-profit forms of business all encourage firms to treat profit as an end. The pursuit of unlimited financial gain and the private distribution of the surplus by for-profit businesses tend to drive the growth of consumerism, environmental degradation, inequality, market concentration, and political capture. In a not-for-profit type of economy, businesses do not have a financial gain purpose or private financial rights. Profit in such a system is used as a means to achieve social benefit. This results in higher levels of equality and opens up the space for more effective sustainability interventions.Yet, relationship-to-profit is only one dimension of business that is important for sustainability. In Paper 4, I develop a framework to structure analyses and wider discussions of post-growth business around five key dimensions of business: (1) relationship-to-profit, (2) incorporation structure, (3) governance, (4) strategy, and (5) size and geographical scope. The theory developed in this thesis offers an explanation of how key institutional elements of business and markets drive social and ecological sustainability outcomes.
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25.
  • Khounlotham, Manirath, et al. (författare)
  • Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis
  • 2012
  • Ingår i: Immunity. - Cambridge, United States : Cell Press. - 1074-7613 .- 1097-4180. ; 37:3, s. 563-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Mice lacking junctional adhesion molecule A (JAM-A, encoded by F11r) exhibit enhanced intestinal epithelial permeability, bacterial translocation, and elevated colonic lymphocyte numbers, yet do not develop colitis. To investigate the contribution of adaptive immune compensation in response to increased intestinal epithelial permeability, we examined the susceptibility of F11r(-/-)Rag1(-/-) mice to acute colitis. Although negligible contributions of adaptive immunity in F11r(+/+)Rag1(-/-) mice were observed, F11r(-/-)Rag1(-/-) mice exhibited increased microflora-dependent colitis. Elimination of T cell subsets and cytokine analyses revealed a protective role for TGF-beta-producing CD4(+) T cells in F11r(-/-) mice. Additionally, loss of JAM-A resulted in elevated mucosal and serum IgA that was dependent upon CD4(+) T cells and TGF-beta. Absence of IgA in F11r(+/+)Igha(-/-) mice did not affect disease, whereas F11r(-/-)Igha(-/-) mice displayed markedly increased susceptibility to acute injury-induced colitis. These data establish a role for adaptive immune-mediated protection from acute colitis under conditions of intestinal epithelial barrier compromise.
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26.
  • Koch, Kristine, et al. (författare)
  • Structure of building blocks in amylopectins
  • 2012
  • Ingår i: Carbohydrate Research. - : Elsevier BV. - 0008-6215 .- 1873-426X. ; 361, s. 105-113
  • Tidskriftsartikel (refereegranskat)abstract
    • Building blocks represent the smallest, branched units found inside clusters of amylopectins. The building blocks from clusters of 10 different amylopectins, representing a wide variety of plants, were isolated and size-fractionated. The unit chain compositions were then analysed. It was found that the number of chains in building blocks increased in proportion to their size similarly in all samples regardless plant source. The smallest blocks (DP 5-9) consisted of 2 chains and the largest blocks (DP >= 45), of which generally only little existed, possessed >= 10 chains. Generally, the degree of branching increased with building block size, but the organisation of chains inside the blocks was unique for each sample. Nevertheless, compared to other plants, amylopectins from cereals (represented by rye, oats, rice and waxy maize) possessing elevated number of the shortest internal B-chains (DP 3-7), tended to have blocks with a lower ratio of A: B-chains, indicative of a preferred Haworth type of structure as opposed to the Staudinger configuration. (C) 2012 Elsevier Ltd. All rights reserved.
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27.
  • Koch, Pierre-Henri, 1988- (författare)
  • Computational methods and strategies for geometallurgy
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • At the interface of geology and mineral processing, geometallurgy is a powerful tool for enhancingresource efficiency. A spatial model that represents the ore body in terms ofmineralogyand physical properties is combined with a process model that describes the concentrationprocess. The performance of a given ore in the process is computed in terms of gradeand recovery of the mineral of interest in the concentrate, but also the presence of potentialpenalty elements and energy costs. The inclusion of ore performance indicators in a blockmodel yields a geometallurgical model that considers the variations in an ore body.Progress has been made in recent years to list and study different processing options interms of data requirements and implementation costs. While providing useful data, littleadvance was made to guide decision-making and to handle uncertainty. The objective has,therefore, been to develop, choose and validate computational methods that suggest optimaldecisions in the scope of geometallurgical strategies for an iron ore and a porphyry copperdeposit.The selected approach is based on an analysis of structure and regularity fromthe ore blockdown to the mineral grains. By selecting the appropriate mathematical tool for each scale,the dimension of the data is reduced and the different scales are then taken into account inmaking decisions. Methods introduced for dimension reduction include machine learningmodels, statistical models and spectral descriptors. The decision models rely on stochasticmulti-armed bandits which are a form of reinforcement learning. The presentation of thedifferent models proceeds by zooming in from coarse scale to fine scale then taking a stepback and analyze the implications. Data that was collected during sampling campaigns andindustrial plant surveys is used to design and verify the proposedmodels.iWith regard to the dimension reduction problem, results showed the method’s ability toclassify mineral textures and identify mineral phases with more than 90 percent accuracy onthe selected data sets of optical images and incorporate different physical properties into ageometallurgical ore type classification. Decision results showed that strategies in the case ofa feed grade control or when different ore types were identified, resulted in a twofold increaseof a reward function which is either Boolean (the product fulfills quality requirements ornot), or continuous (an economic objective). The cumulative value of the reward functionmeasured the optimality of a processing strategy. Quantitative methods were introduced toevaluate ore classification as well as geometallurgical strategies.The achieved results suggest the introduction of these computationalmethods in the practiceof geometallurgy. The increased knowledge of different ore type performances and appropriatemodels lead to optimal decisions for improved resource efficiency along the ore valuechain. This is achieved by bothmaximizing profit and decreasing environmental impact, forexample by choosing processing routes that minimize energy consumption.
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28.
  • Koch, Pierre-Henri, et al. (författare)
  • Textural Variants of Iron Ore from Malmberget : Characterisation, Comminution and Mineral Liberation
  • 2013
  • Ingår i: Exploration, Resource & Mining Geology Conference 2013. - Cardiff, Wales, UK : The Australian Institute of Mining and Metallurgy.
  • Konferensbidrag (refereegranskat)abstract
    • The Geometallurgy combines geology and mineralogy, processing techniques and metallurgy into spatially-based predictive model and is useful tool that can be used in production management of a mineral processing plant. This work presents characterisation of different textural variants of the breccia iron ore from Malmberget, Northern Sweden, an iron mine operated by Luossavaara-Kiirunavaara Aktiebolag (LKAB). Experimental work includes point load tests, compressive tests, and laboratory grinding and liberation measurements of the products. The motivation of this work is based on the need of the industry to predict the throughput, particle size distribution, modal mineralogy, mineral textures and specific energy of the material.Around Magnetite orebodies, a wide range of feldspar-rich iron ore breccia has been described and classified by Lund, Lamberg (2013a) into eight different classes according to their feldspar content. The two end-members exhibit, respectively, a high iron grade (low feldspar content) and low iron grade (high feldspar content). A definition for the micro texture (micro fabrics) used in this study has been developed by Lund, Lamberg and Lindberg (2013b): two sample are texturally different if their modally refined liberation distribution is different in a given particle size. The hypothesis of the study is that it should be possible to quantitatively describe the textures of Malmberget feldspar type with two textural archetypes: high-graded massive and low-graded disseminated. The sample used were named after the earlier classification from CF1 (low iron grade) to CF8 (high iron grade) and compared per class. After simple rock mechanics tests, the second step involved comminution with a jaw crusher with 5 mm opening followed by 20 minutes in a ball mill with 1L of water for 1.2 kg of material. The 53 to 75 µm size fraction was selected for further characterisation and liberation analysis with x-ray fluorescence (XRF) and scanning electron microscope (SEM).The point load tests and compressive tests showed good agreement. When combined with specific gravity measurements, these properties allowed grouping of the eight classes into three clusters instead of the two end-members proposed initially. The jaw crusher and ball mill sieving curves further more supported this classification.The study with a SEM using INCA Mineral software and HSC Geo provided information on modal mineralogy, particles and degree of liberation in the 53 to 75 µm size fraction. Using these results, an association index (AI), describing how gangue minerals are associated with magnetite in the ore breccia, was calculated. Preliminary linear models predicting a relative work index for ball mill, the reduction ratio for jaw crusher and the degree of liberation of magnetite-based on modal mineralogy or mechanical properties were developed.While further work is required, this study shown the relevance and practical utility of the method used and indicates a relation between mechanical strength, iron ore grade, physical properties and textural information. The main hypothesis of two end-members had to be rejected and three classes were introduced instead, due to the large variability of breccia. Additional studies could include a higher number of samples, evaluate which mechanical tests are relevant in a context of geometallurgy, find a way to directly measure the AI and describe the effect of mixing different kinds of ore breccia before comminution in terms of particles, energy consumption and liberation
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29.
  • Koch, Sina, et al. (författare)
  • NRP1 Presented in trans to the Endothelium Arrests VEGFR2 Endocytosis, Preventing Angiogenic Signaling and Tumor Initiation
  • 2014
  • Ingår i: Developmental Cell. - : Elsevier BV. - 1534-5807 .- 1878-1551. ; 28:6, s. 633-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuropilin 1 (NRP1) modulates angiogenesis by binding vascular endothelial growth factor (VEGF) and its receptor, VEGFR2. We examined the consequences when VEGFR2 and NRP1 were expressed on the same cell (cis) or on different cells (trans). In cis, VEGF induced rapid VEGFR2/NRP1 complex formation and internalization. In trans, complex formation was delayed and phosphorylation of phospholipase C gamma (PLC gamma) and extracellular regulated kinase 2 (ERK2) was prolonged, whereas ERK1 phosphorylation was reduced. Trans complex formation suppressed initiation and vascularization of NRP1-expressing mouse fibrosarcoma and melanoma. Suppression in trans required high-affinity, steady-state binding of VEGF to NRP1, which was dependent on the NRP1 C-terminal domain. Compatible with a trans effect of NRP1, quiescent vasculature in the developing retina showed continuous high NRP1 expression, whereas angiogenic sprouting occurred where NRP1 levels fluctuated between adjacent endothelial cells. Therefore, through communication in trans, NRP1 can modulate VEGFR2 signaling and suppress angiogenesis.
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30.
  • Källman, Anna, et al. (författare)
  • On the interconnection of clusters and building blocks in barley amylopectin
  • 2013
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 55, s. 75-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Amylopectin is a highly branched starch component built up of a large number of clustered alpha-D-glucose chains. A single C-chain possesses the reducing end and carries the rest of the macromolecule. The aim of this study was to investigate the interconnection of clusters and domains (groups of clusters) in barley amylopectin by isolation of the units with a-amylolysis and subsequent labelling of the C-chain in the phi,beta-limit dextrins of these structural units with the fluorescent compound 2-aminopyridine. Because these C-chains were formed by alpha-amylolysis of B-chains in amylopectin, they were designated bc-chains to be distinguished from C-chains in amylopectin. Four barley samples were selected for the study, of which two had the amo1 genetic background. Longer bc-chains were found in domains suggesting their role in cluster interconnection. The average chain length of bc-chains was longer than the average chain length of B-chains and the size-distribution of the bc-chains was unimodal implying that the bc-chains comprise a unique category of chains. Extensive alpha-amylolysis of labelled amylopectin and clusters revealed the distribution of branched building blocks situated at the reducing end of these molecules. Any type of size group of building blocks can be situated at the reducing end, because the size-distribution of these blocks was similar to the distribution of all building blocks present in the sample. This suggested certain randomness in the distribution of the types of building blocks within the amylopectin macromolecule. (c) 2013 Elsevier B.V. All rights reserved.
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31.
  • Källman, Anna, et al. (författare)
  • Starch structure in developing barley endosperm
  • 2015
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 81, s. 730-735
  • Tidskriftsartikel (refereegranskat)abstract
    • Barley spikes of the cultivars/breeding lines Gustav, Karmose and SLU 7 were harvested at 9, 12 and 24 days after flowering in order to study starch structure in developing barley endosperm. Kernel dry weight, starch content and amylose content increased during development. Structural analysis was performed on whole starch and included the chain-length distribution of the whole starches and their beta-limit dextrins. Karmose, possessing the amo1 mutation, had higher amylose content and a lower proportion of long chains (DP >= 38) in the amylopectin component than SLU 7 and Gustay. Structural differences during endosperm development were seen as a decrease in molar proportion of chains of DP 22-37 in whole starch. In beta-limit dextrins, the proportion of B-fp-chains (DP 4-7) increased and the proportion of BSmajor-chains (DP 15-27) decreased during development, suggesting more frequent activity of starch branching enzymes at later stages of maturation, resulting in amylopectin with denser structure. (C) 2015 Elsevier B.V. All rights reserved.
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32.
  • Källman, Anna, et al. (författare)
  • Thermal properties of barley starch and its relation to starch characteristics
  • 2015
  • Ingår i: International Journal of Biological Macromolecules. - : Elsevier BV. - 0141-8130 .- 1879-0003. ; 81, s. 692-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Amylopectin fine structure and starch gelatinization and retrogradation were studied in 10 different barley cultivars/breeding lines. Clusters and building blocks were isolated from the amylopectin by alpha-amylase from Bacillus amyloliquefaciens and their structure was characterized. Gelatinization was studied at a starch:water ratio of 1:3, and retrogradation was studied oil gelatinized starch at starch:water ratio of 1:2, by differential scanning calorimetry. Three barley cultivars/breeding lines possessed the amo1 mutation, and they all had a lower molar proportion of chains of DP >= 38 and more of large building blocks. The amo1 mutation also resulted in a higher gelatinization temperature and a broader temperature interval during gelatinization. Overall, small clusters with a dense structure resulted in a higher gelatinization temperature while retrogradation was promoted by short chains in the amylopectin and many large building blocks. (C) 2015 Elsevier B.V. All rights reserved.
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33.
  • Lawrence, Maggie, et al. (författare)
  • Stroke secondary prevention, a non-surgical and non-pharmacological consensus definition: results of a Delphi study
  • 2019
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Evidence supporting lifestyle modification in vascular risk reduction is limited, drawn largely from primary prevention studies. To advance the evidence base for non-pharmacological and non-surgical stroke secondary prevention (SSP), empirical research is needed, informed by a consensus-derived definition of SSP. To date, no such definition has been published. We used Delphi methods to generate an evidence-based definition of non-pharmacological and non-surgical SSP. RESULTS: The 16 participants were members of INSsPiRE (International Network of Stroke Secondary Prevention Researchers), a multidisciplinary group of trialists, academics and clinicians. The Elicitation stage identified 49 key elements, grouped into 3 overarching domains: Risk factors, Education, and Theory before being subjected to iterative stages of elicitation, ranking, discussion, and anonymous voting. In the Action stage, following an experience-based engagement with key stakeholders, a consensus-derived definition, complementing current pharmacological and surgical SSP pathways, was finalised: Non-pharmacological and non-surgical stroke secondary prevention supports and improves long-term health and well-being in everyday life and reduces the risk of another stroke, by drawing from a spectrum of theoretically informed interventions and educational strategies. Interventions to self-manage modifiable lifestyle risk factors are contextualized and individualized to the capacities, needs, and personally meaningful priorities of individuals with stroke and their families.
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34.
  •  
35.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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36.
  • Plue, Jan, et al. (författare)
  • European soil seed bank communities across a climate and land-cover gradient
  • 2020
  • Annan publikationabstract
    • This is the data set used for the publication Buffering effects of soil seed banks on plant community composition in response to land use and climate, published in the journal Global Ecology and Biogeography.Aim.Climate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life-history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this.Location. EuropeTime period. 1978 – 2014Major taxa studied. Flowering plantsMethods.Using a space-for-time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient.Results.Soil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer.Main conclusions.High seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life-history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time-lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected.MethodsThis dataset is a collection of 41 published and 5 unpublished data sets, consisting of 2796 plots with corresponding seed bank and herb layer community data. Sampling effort varied across data sets, but involved sampling of the soil and subsequent germination trials in a greenhouse to determine seed bank composition. Herb layer communities were determined by the identification of plants in relevés. Please consult the readme file and published paper for further details.Usage NotesPlease contact database or individual data set authors for further information and collaboration when using the data set or any of its component parts. Please also note that some of these data sets have already been published alongside their orginal papers. Finally, please cite data and datasets according to community standards.
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37.
  • Qasem, Apan, et al. (författare)
  • Lightning Talks of EduHPC 2022
  • 2022
  • Ingår i: 2022 IEEE/ACM INTERNATIONAL WORKSHOP ON EDUCATION FOR HIGH PERFORMANCE COMPUTING (EDUHPC). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 42-49
  • Konferensbidrag (refereegranskat)abstract
    • The lightning talks at EduHPC provide an opportunity to share early results and insights on parallel and distributed computing (PDC) education and training efforts. The four lightning talks at EduHPC 2022 cover a range of topics in broadening PDC education: (i) curriculum development efforts for the European Masters in HPC program, (ii) bootcamps for CI professionals who support the running of AI workloads on HPC systems, (iii) a GPU programming course following the Carpentries model and (iv) peer-review assignments to help students write efficient parallel algorithms within sustainable software libraries.
  •  
38.
  • Zhang, Fan, et al. (författare)
  • VEGF-B is dispensable for blood vessel growth but critical for their survival, and VEGF-B targeting inhibits pathological angiogenesis
  • 2009
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:15, s. 6152-6157
  • Tidskriftsartikel (refereegranskat)abstract
    • VEGF-B, a homolog of VEGF discovered a long time ago, has not been considered an important target in antiangiogenic therapy. Instead, it has received little attention from the field. In this study, using different animal models and multiple types of vascular cells, we revealed that although VEGF-B is dispensable for blood vessel growth, it is critical for their survival. Importantly, the survival effect of VEGF-B is not only on vascular endothelial cells, but also on pericytes, smooth muscle cells, and vascular stem/progenitor cells. In vivo, VEGF-B targeting inhibited both choroidal and retinal neovascularization. Mechanistically, we found that the vascular survival effect of VEGF-B is achieved by regulating the expression of many vascular prosurvival genes via both NP-1 and VEGFR-1. Our work thus indicates that the function of VEGF-B in the vascular system is to act as a "survival," rather than an "angiogenic" factor and that VEGF-B inhibition may offer new therapeutic opportunities to treat neovascular diseases.
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