| 1. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 2. |
- Carstensen, Jacob, et al.
(författare)
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Factors regulating the coastal nutrient filter in the Baltic Sea
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:6, s. 1194-1210
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Tidskriftsartikel (refereegranskat)abstract
- The coastal zone of the Baltic Sea is diverse with strong regional differences in the physico-chemical setting. This diversity is also reflected in the importance of different biogeochemical processes altering nutrient and organic matter fluxes on the passage from land to sea. This review investigates the most important processes for removal of nutrients and organic matter, and the factors that regulate the efficiency of the coastal filter. Nitrogen removal through denitrification is high in lagoons receiving large inputs of nitrate and organic matter. Phosphorus burial is high in archipelagos with substantial sedimentation, but the stability of different burial forms varies across the Baltic Sea. Organic matter processes are tightly linked to the nitrogen and phosphorus cycles. Moreover, these processes are strongly modulated depending on composition of vegetation and fauna. Managing coastal ecosystems to improve the effectiveness of the coastal filter can reduce eutrophication in the open Baltic Sea.
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| 3. |
- Andersson, Isabelle, et al.
(författare)
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The IT Phenomenon in the Multinational Enterprise
- 2012
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Annan publikation (populärvet., debatt m.m.)abstract
- ForewordIn the last ten years (that I have been doing research and teaching at Mälardalen University) I have studied how information technology has become increasingly important in companies’ activities – in their daily business as well as in its implications for firms in general. What occurs to me is that, when the issue becomes a topic of academic research, information technology is studied from different perspectives in different areas of research – sometimes it is treated as a topic in itself, and sometimes as part of a business strategy or marketing activity. I have often asked myself when information technology will become regarded as an aspect of the business administration taught at universities. To some extent I think it already is, although it is not yet formally considered to be an aspect of business administration.As a lecturer, I have focused mainly on international business. In many of the seminars that I have lead, the issue of information technology has been discussed as something that the students believe will change the way that multinational enterprises can and do coordinate and control their organisations and acquire the information they need concerning their markets. (The use of information technology states that that is the case). The issue of how and to what end multinational enterprises use information technology has often been raised, but it seems that the literature comes up short in providing a holistic view of this matter. There are many studies on different aspects, and some of them present empirical data, but it seems there is a lack of major contemporary studies showing general results on the phenomenon of information technology in multinational enterprises. This is no surprise, since a study of this kind would cost a great deal of resources in terms of time as well as professors and doctoral candidates.This book is a work that partly fills the gap in the literature. It discusses and assembles literature on information technology as a feature of the multinational enterprise, but to some extent it also theorises on the role of IT in multinational enterprises. The students behind this work have carried out extensive literature reviews in many of the fields that encompass information technology in business in general and in large international companies in particular. They have arranged the literature and present it in a way they think is suitable in order to provide an overall picture of information technology in multinational enterprises. The study of the literature has thrown up questions, which have been asked of representatives of multinational companies and so “cases” are presented, i.e.Iexamples demonstrating the use of information technology. As a whole, this book fulfils its aim, which is to present the use of information technology in multinational companies in theory and in practice and to show that information technology as used by companies is a part of business administration as we know it. Of course there are questions that remain unanswered. Some of them are stated as topics for further research at the end of this work.I feel content to use this book as a textbook on undergraduate courses dealing with the management of multinational enterprises, since the use of information technology is an important part of these. I feel proud that it is my students who (may I add, without much help from my part) have produced this work.Cecilia Lindh, supervisor
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| 4. |
- Angove, Charlotte, et al.
(författare)
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Assessing the efficiencies and challenges for nutrient uptake by aquatic plants
- 2018
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Ingår i: Journal of Experimental Marine Biology and Ecology. - : Elsevier BV. - 0022-0981 .- 1879-1697. ; 507, s. 23-30
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Tidskriftsartikel (refereegranskat)abstract
- Aquatic plant meadows are valuable components to the 'coastal filter' and it is important to understand the processes that drive their ability to cycle nutrients. However, at present, the field-based evidence for understanding the drivers of nutrient uptake by plants is lacking. This study aimed to investigate how well individual shoots of aquatic plants could meet their nitrogen demands using the sediment nutrient pool (porewater ammonium) and to explore which traits helped to facilitate such uptake. Several species were investigated in shallow, submerged (2-4 m) mixed-species communities in the northern Baltic Sea using incubation experiments with enriched ammonium. After a 3.5 h incubation time, individuals were collected and analysed for nitrogen (% DW) and N-15 (at-%) concentrations. Uptake by plants was calculated per unit nitrogen in response to the N-15 labelled source and to overall nitrogen availability. Background porewater ammonium availability was highly variable between individual plants. Species identity did not significantly affect uptake metrics and the effect of ambient porewater availability was weak. As biomass increased there were significant logarithmic declines in the 95th quantiles of nutrient uptake rates, ambient porewater nutrient availability and aboveground nitrogen tissue concentrations (% DW). Such findings suggested that uptake rates of plants were significantly demand driven and the nutrient conditions of the porewater were significantly driven by the demands of the plant. Findings parameterised the unfulfilled potential for some aquatic plants to cycle nutrients more efficiently and highlighted the potential importance of access to new nutrient sources as a way of enhancing nutrient cycling by aquatic plants. Plant traits and community properties such as the activity of infauna could facilitate such an access and are likely important for nutrient uptake.
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| 5. |
- Angove, Charlotte, et al.
(författare)
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The Fight to Capture Light : Functional Diversity Is Related to Aquatic Plant Community Productivity Likely by Enhancing Light Capture
- 2020
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Functional diversity (FD) experiments are highly effective for investigating how a community interacts with its environment. However, such experiments using morphological and chemical traits have not been conducted for submerged aquatic plants and their insights would be highly valuable for understanding the ecology of these communities. We conducted a 15-week field experiment in the Baltic Sea where we manipulated the species composition of aquatic plant communities to investigate functional diversity. We constructed artificial triculture communities with different species compositions to change the Community Weighted Means (CWMs) and variability of traits. We measured nine plant traits and tested how community productivity (CP) was related to FD, trait CWMs and community trait ranges. CP varied by more than four times across treatments and functional richness was significantly related to CP. Functional evenness and functional divergence were not significantly related to CR Height, leaf area and delta C-13 were significantly related to CP. Leaf delta C-13 trends with CP suggested that the carbon supply is not replete, yet species composition was partly responsible for the relationship. Plant height likely had multifaceted benefits to CP because there was evidence of a competitive height interaction between the tallest and 2 nd tallest species, therefore the effects of plant height to CP would have been disproportionally large. The height of the tallest species significantly drove the variability of the community height range, which was significantly related to CP and it had a relatively large influence on the calculation of FD indices. Leaf area, which was strongly correlated to plant height, was also significantly related to CR The significant relationship between functional richness and CP was most likely driven by the presence of taller plants. FD likely enhanced CP, by selecting for extreme trait values which enhanced production (selection effect), while niche complementarity effects were not observed. This study provides experimental evidence and mechanistic insights into the role of FD and specific traits for CP in submerged aquatic plant communities. To conclude, FD was significantly related to CP of temperate aquatic plant communities likely by selecting for traits which enhanced light capture, with consequences for carbon supply.
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| 6. |
- Asmala, Eero, et al.
(författare)
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Role of Eelgrass in the Coastal Filter of Contrasting Baltic Sea Environments
- 2019
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Ingår i: Estuaries and Coasts. - : Springer Science and Business Media LLC. - 1559-2723 .- 1559-2731. ; 42:7, s. 1882-1895
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Tidskriftsartikel (refereegranskat)abstract
- Coastal ecosystems act as filters of nutrients from land to the open sea. We investigated the role of eelgrass (Zostera marina) metabolism in the coastal filter transforming nitrogen, phosphorus, and organic carbon. Field campaigns following identical methodologies were carried out at two contrasting coastal locations: the mesohaline and nutrient-rich Roskilde Fjord, Denmark, and the mesotrophic brackish Tvarminne archipelago, Finland. Over the 24-h in situ benthic incubations, we measured oxygen concentrations continuously and assessed changes in DOM characteristics and net fluxes of carbon, nitrogen, and phosphorus. Ecosystem metabolism modeled on the basis of the O-2 data showed that the systems were either net heterotrophic (Roskilde Fjord; - 1.6 and - 2.4 g O-2 m(-2) day(-1) in eelgrass meadow and bare sand, respectively) or had balanced primary production and respiration (Tvarminne; 0.0 and 0.2 g O-2 m(-2) day(-1)). Overall, initial nutrient stoichiometry was a key factor determining benthic-pelagic fluxes of nutrients, which exacerbated the deviations from Redfield ratios of N and P, indicating an efficient use of the limiting nutrient. A net diel uptake of dissolved inorganic N was observed at both locations (- 2.3 mu mol l(-1) day(-1) in Roskilde Fjord and - 0.1 mu mol l(-1) day(-1) in Tvarminne). Despite minor changes in dissolved organic carbon concentrations during the incubations, a marked increase of fluorescent DOM was observed at both locations, suggesting rapid heterotrophic processing of the DOM pool. Our results underline that the biogeochemical role of eelgrass in the coastal filter is not inherent, but strongly dependent on the environmental conditions.
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| 7. |
- Backman, Ellen, 1981-, et al.
(författare)
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Metoder för att stimulera språk och kommunikation hos barn, ungdomar och vuxna inom habiliteringen
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Språkliga och kommunikativa begränsningar är vanligt förekommande vid ett flertal av de diagnoser och tillstånd som återfinns hos personer inom habiliteringsverksamheter i Sverige och förutsätter en tvärprofessionell och långvarig insats. Syftet med föreliggande arbete är att systematiskt beskriva bästa tillgängliga evidens avseende interventioner fokuserade på språklig och kommunikativ förmåga för personer med medfödda funktionsnedsättningar från sex års ålder och uppåt inom habiliteringsverksamhet. Arbetet kan ses som en fortsättning på EBH-rapporten ”Tidiga kommunikations- och språkinsatser till förskolebarn”.Internationellt publicerade interventionsstudier från de senaste 15 åren med fokus på språkliga och kommunikativa förmågor vid typiskt förekommande diagnoser inom habiliteringsverksamhet granskades och sammanfattades. Initialt inkluderades endast översiktsartiklar och metaanalyser, men då dessa till största delen hade fokus på autism och/eller Alternativ och Kompletterande Kommunikation (AKK) utökades sökningen till att även inkludera ett antal primärstudier med annat fokus. Rapporten omfattar 67 studier.Resultatet visar att ”stark rekommendation att använda” (enligt GRADE) endast förekommer i begränsad utsträckning, och när det förekommer är det vid insatser relaterade till autism och/eller AKK. ”Stark rekommendation att inte använda” finns vid insatser relaterade till akupunktur/akupressur och faciliterad kommunikation. Det kan konstateras att det finns en stor brist på studier avseende vuxna personer respektive intellektuell funktionsnedsättning.Detta arbete tillför ytterligare kunskap till området för evidensbaserade insatser vid svårigheter när det gäller kommunikation och språk, och visar att evidens i strikt bemärkelse är svår att erhålla bland annat beroende på de små och heterogena patientgrupperna och, som en konsekvens av detta, en brist på stora randomiserade studier.
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| 8. |
- Baden, Susanne P., 1952, et al.
(författare)
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Effects of depth and overgrowth of ephemeral macroalgae on a remote subtidal NE Atlantic eelgrass (Zostera marina) community
- 2022
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Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a short-term field sampling complemented with time integrating stable isotope analysis to ho- listically investigate status and ecological interactions in a remote NE Atlantic Zostera marina meadow. We found high nutrient water concentrations, large biomass of fast-growing, ephemeral macroalgae, low abundance, and biodiversity of epifauna and a food web with thornback ray (Raja clavata) as intermediate and cod (Gadus morhua) as top predator. We observed no variation with increasing depth (3.5–11 m) except for decreasing shoot density and biomass of Zostera and macroalgae. Our results indicate that the Finnøya Zostera ecosystem is eutrophicated. During the past three to four decades, nutrients from aquaculture have steadily increased to reach 75% of anthropogenic input while the coastal top predator cod has decreased by 50%. We conclude that bottom-up regulation is a predominant driver of change since top-down regulation is generally weak in low density and exposed Zostera ecosystems such as Finnøya.
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| 9. |
- Berglund, Camilla, 1970-
(författare)
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Närheter och avstånd i ett nordvärmländskt skogslandskap : Praktiker och betydelser i nya tidsrumsliga sammanhang
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the contemporary forest landscape of northern Värmland in Sweden in terms of practices, meanings and time-space relations. The increasing urbanization worldwide also affects the countryside landscape to produce what is generally referred to as “new ruralities”, which are the result of changed conditions for livelihood and leisure. What does the concept new ruralities mean in relation to the sparsely populated forest landscape of northern Värmland, Sweden?The thesis adopts a relational approach to landscape, which means that landscape entails and forms relations between the material, the immaterial, and the human. Landscapes stretches out in time and space, which means that they rests on and progresses from layers of earlier and contemporary activities. Landscape practices and meanings are therefore important for understanding changes as well as continuities in the context of new ruralities. Inspired by the Heideggerian basic assumption about dwelling the thesis methodologically draws on phenomenology, but also on ethnography to clarify the relation between the individual and the society. Interviews, field studies and participant observations with special focus on the settlement, community engagement, and forest and hunting were conducted in four parishes in northern Värmland.Proximity and distance turn out to be the common denominators in the meanings of the forest landscape that emerge from the study, but attention is also clearly drawn to the problems of depopulation, changing social relations, and the tension between the private and the common good. The new ruralities of the northern Värmland forest landscape seem to rest on the tension between flow and fixity, between change and continuity, as traditional practices are performed with new meanings and extended time-space relations.
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| 10. |
- Bergqvist, Jonas, et al.
(författare)
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Sub-glass transition annealing enhances polymer solar cell performance
- 2014
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488. ; 2:17, s. 6146-6152
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Tidskriftsartikel (refereegranskat)abstract
- Thermal annealing of non-crystalline polymer: fullerene blends typically results in a drastic decrease in solar cell performance. In particular aggressive annealing above the glass transition temperature results in a detrimental coarsening of the blend nanostructure. We demonstrate that mild annealing below the glass transition temperature is a viable avenue to control the nanostructure of a non-crystalline thiophene-quinoxaline copolymer: fullerene blend. Direct imaging methods indicate that coarsening of the blend nanostructure can be avoided. However, a combination of absorption and luminescence spectroscopy reveals that local changes in the polymer conformation as well as limited fullerene aggregation are permitted to occur. As a result, we are able to optimise the solar cell performance evenly across different positions of the coated area, which is a necessary criterion for large-scale, high throughput production.
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