| 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. |
- Cedervall, Johan, et al.
(författare)
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Magnetocaloric effect in Fe2 P: Magnetic and phonon degrees of freedom
- 2019
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Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 99:17
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Tidskriftsartikel (refereegranskat)abstract
- Devices based on magnetocaloric materials provide great hope for environmentally friendly and energy efficient cooling that does not rely on the use of harmful gasses. Fe2P based compounds are alloys that have shown great potential for magnetocaloric devices. The magnetic behavior in Fe2P is characterized by a strong magnetocaloric effect that coexists with a first-order magnetic transition (FOMT). Neutron diffraction and inelastic scattering, Mossbauer spectroscopy, and first-principles calculations have been used to determine the structural and magnetic state of Fe2P around the FOMT. The results reveal that ferromagnetic moments in the ordered phase are perturbed at the FOMT such that the moments cant away from the principle direction within a small temperature region. The acoustic-phonon modes reveal a temperature-dependent nonzero energy gap in the magnetically ordered phase that falls to zero at the FOMT. The interplay between the FOMT and the phonon energy gap indicates hybridization between magnetic modes strongly affected by spin-orbit coupling and phonon modes leading to magnon-phonon quasiparticles that drive the magnetocaloric effect.
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| 3. |
- Andersson, Martin, 1988, et al.
(författare)
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Abatement cost of embodied emissions of a residential building in Sweden
- 2018
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Ingår i: Energy and Buildings. - : Elsevier BV. - 0378-7788. ; 158, s. 595-604
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Tidskriftsartikel (refereegranskat)abstract
- In 2010, the world’s buildings accounted for approximately 19% of all greenhouse gas emissions. These emissions stem from both the construction and operation of buildings. In recent years the carbon efficiency of energy sources and energy efficiency of new buildings has been improved in Sweden. Therefore, embodied emissions accounts for an increasing share of the life cycle emissions of new buildings. This study aims to asses the cost effectiveness in abatement of embodied emissions. This was done by assessing the embodied emissions of a case building and several conventional design measures along with the implication on production cost. It was found that many of the measures enabled cost effective carbon abatement. Embodied emissions could be reduced by 15% using cost neutral or nearly cost neutral measures. Abatements up to 18% were found cost effective in relation to abatement of carbon dioxide emissions in other sectors. Abatements up to 24% were possible with minor increases in total production cost (0.22%) even though some of the individual measures were found expensive in relation to abatement of carbon dioxide emissions in other sectors. Some measures entailed increased floor area that could potentially lead to economic gain where exterior area is a limiting factor. Acoustic requirements were found to be a limiting factor in abatement of embodied emissions.
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| 4. |
- Bergström, Göran, et al.
(författare)
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Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis : The Swedish CardioPulmonary BioImage Study
- 2024
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Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 5. |
- Tanyeli, Irem, 1988, et al.
(författare)
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Nanoplasmonic NO 2 Sensor with a Sub-10 Parts per Billion Limit of Detection in Urban Air
- 2022
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Ingår i: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 7:4, s. 1008-1018
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Tidskriftsartikel (refereegranskat)abstract
- Urban air pollution is a critical health problem in cities all around the world. Therefore, spatially highly resolved real-time monitoring of airborne pollutants, in general, and of nitrogen dioxide, NO2, in particular, is of utmost importance. However, highly accurate but fixed and bulky measurement stations or satellites are used for this purpose to date. This defines a need for miniaturized NO2 sensor solutions with detection limits in the low parts per billion range to finally enable indicative air quality monitoring at low cost that facilitates detection of highly local emission peaks and enables the implementation of direct local actions like traffic control, to immediately reduce local emissions. To address this challenge, we present a nanoplasmonic NO2 sensor based on arrays of Au nanoparticles coated with a thin layer of polycrystalline WO3, which displays a spectral redshift in the localized surface plasmon resonance in response to NO2. Sensor performance is characterized under (i) idealized laboratory conditions, (ii) conditions simulating humid urban air, and (iii) an outdoor field test in a miniaturized device benchmarked against a commercial NO2 sensor approved according to European and American standards. The limit of detection of the plasmonic solution is below 10 ppb in all conditions. The observed plasmonic response is attributed to a combination of charge transfer between the WO3 layer and the plasmonic Au nanoparticles, WO3 layer volume expansion, and changes in WO3 permittivity. The obtained results highlight the viability of nanoplasmonic gas sensors, in general, and their potential for practical application in indicative urban air monitoring, in particular.
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| 6. |
- Adiels, Martin, 1976, et al.
(författare)
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Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia
- 2019
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Ingår i: Diabetes, obesity and metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 21:8, s. 1861-1870
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Tidskriftsartikel (refereegranskat)abstract
- - Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics. Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- 2 H 3 ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy. Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes. Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions: The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III. © 2019 John Wiley & Sons Ltd
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| 7. |
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| 8. |
- ANDERSSON, MICHAEL, 1988, et al.
(författare)
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Feasibility of Ambient RF Energy Harvesting for Self-Sustainable M2M Communications Using Transparent and Flexible Graphene Antennas
- 2016
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 4, s. 5850-5857
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Tidskriftsartikel (refereegranskat)abstract
- Lifetime is a critical parameter in ubiquitous, battery-operated sensors for machine-to-machine (M2M) communication systems, an emerging part of the future Internet of Things. In this practical article, the performance of radio frequency (RF) to DC energy converters using transparent and flexible rectennas based on graphene in an ambient RF energyharvesting scenario is evaluated. Full-wave EM simulations of a dipole antenna assuming the reported state-of-the-art sheet resistance for few-layer, transparent graphene yields an estimated ohmic efficiency of 5 %. In the power budget calculation, the low efficiency of transparent graphene antennas is an issue because of the relatively low amount of available ambient RF energy in the frequency bands of interest, which together sets an upper limit on the harvested energy available for the RF-powered device. Using a commercial diode rectifier and an off-the-shelf wireless system for sensor communication, the graphene-based solution provides only a limited battery lifetime extension. However, for ultra-low-power technologies currently at the research stage, more advantageous ambient energy levels, or other use cases with infrequent data transmission, graphene-based solutions may be more feasible.
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| 9. |
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| 10. |
- Andersson, Martin, 1988-
(författare)
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How soldiers' women built early modern states : Stockholm 1544–1635
- 2021
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Ingår i: Bringing the People Back In : State Building from Below in the Nordic Countries ca. 1500-1800. - First edition. | New York : Routledge, 2021. | Series: Routledge research in early modern history : Routledge. - 9780367686963 - 9781003138662 ; , s. 162-180
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- To study soldiers' women forming military households as a form of state building is an attempt to expand ‘the below’-perspective beyond its inherited reliance upon studies of ‘the local.’ Early modern state building meant the creation of several new such socio-economic niches, of which soldier's woman was one. After some theoretical and methodological discussion, it first establishes when and how soldier's woman became a socio-economic niche in early modern Sweden, before exploring the characteristics of that niche and the women who lived in it. Compared to other urban settings, soldiers' women should thus be more common in Stockholm – which is why there is a sufficient volume of records available to be analysed to begin with. Viewing early modern military household formation as everyday politics of state building thus shows how its results could be unintended not just from below, but also from the very top.
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