| 141. |
- Piel, Sarah, et al.
(författare)
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Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF’s protective mechanisms and optimize its therapeutic application in post-arrest care.
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| 142. |
- Rader, Erika, et al.
(författare)
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Preferably Plinian and Pumaceous : Implications of Microbial Activity in Modern Volcanic Deposits at Askja Volcano, Iceland, and Relevancy for Mars Exploration
- 2020
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Ingår i: ACS Earth and Space Chemistry. - : American Chemical Society (ACS). - 2472-3452. ; 4:9, s. 1500-1514
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Tidskriftsartikel (refereegranskat)abstract
- To search more efficiently for a record of past life on Mars, it is critical to know where to look and thus maximize the likelihood of success. Large-scale site selection for the Mars 2020 mission has been completed, but small (meter to 10 cm)-scale relationships of microenvironments will not be known until the rover reaches the surface. Over a 2 m transect at a modern volcanic deposit on the flank of Askja volcano in the barren highlands of Iceland, we compared two biological indicators (ATP activity and 16SrRNA amplicon sequence composition) to physical characteristics including bulk chemical composition, spectral signatures of mineralogy, and grain size. Using analytical instrumentation analogous to those available on Mars rovers, we were able to characterize the geological setting of the deposits and link physical parameters to microbial abundance and diversity. In general, methanogenesis, methanotrophy/methylotrophy, and nitrate reduction were the functional traits most associated with microbial community shift along the transect. Core microbiome members tended to be associated with nitrate reduction, and relative abundance of core microbes was strongly related to free water in the deposit. Community compositional shift of the rare microbiome was related to microenvironmental changes such as change in grain size, geochemistry, and age of deposit. These correlations lead us to suggest a sampling strategy that accounts for Martian geology, looking for undisturbed (not remobilized) explosive volcanic ash below pumice that could maximize diversity and abundance of different bioindicators. Our study also illustrates the importance of studying the variability across microenvironments in low biomass settings on earth.
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| 143. |
- Roche, Dominique G., et al.
(författare)
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Behavioural lateralization in a detour test is not repeatable in fishes
- 2020
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Ingår i: Animal Behaviour. - : Elsevier BV. - 0003-3472 .- 1095-8282. ; 167, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural lateralization, the asymmetric expression of cognitive functions, is reported to enhance key fitness-relevant traits such as group coordination, multitasking and predator escape. Therefore, studies reporting negative effects on lateralization in fish due to environmental stressors such as ocean acidification, hypoxia and pollutants are worrisome. However, such studies tend to use a detour test and focus on population level measures, without validating whether lateralization is consistent within individuals across time. We conducted a multispecies, international assessment of the repeatability (R) of lateralization in four previously studied fish species using a detour test (T-maze), a common method for testing lateralization. We also reanalysed a published data set on a fifth species using new statistical methods. We expected the three shoaling species to exhibit greater within-individual consistency in lateralization than their nonshoaling counterparts given previous reports of stronger lateralization in group-living fishes. Absolute and relative lateralization scores were highly nonrepeatable in all five species (0.01<R<0.08), irrespective of their shoaling status. We carefully reviewed 31 published studies in which the detour test was employed to examine lateralization in fish and identified statistical issues in all of them. We develop and propose new statistical analyses to test for population and individual level lateralization. The commonly used detour test does not appear to be appropriate for quantifying behavioural lateralization in fishes, calling into question functional inferences drawn by many published studies, including our own. Potential fitness benefits of lateralization and anthropogenic effects on lateralization as a proxy for adaptive brain functioning need to be assessed with alternative paradigms.
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| 144. |
- Roels, Juliette, et al.
(författare)
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Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia
- 2020
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Ingår i: Blood cancer discovery. - : American Association for Cancer Research. - 2643-3249. ; 1:3, s. 274-289
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Tidskriftsartikel (refereegranskat)abstract
- Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.
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| 145. |
- Schlosser, Pascal, et al.
(författare)
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Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine
- 2023
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Ingår i: Nature Genetics. - 1546-1718. ; 55:6, s. 995-1008
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Tidskriftsartikel (refereegranskat)abstract
- The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite-disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.
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| 146. |
- Schulze, Steve, et al.
(författare)
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The Palomar Transient Factory Core-collapse Supernova Host-galaxy Sample. I. Host-galaxy Distribution Functions and Environment Dependence of Core-collapse Supernovae
- 2021
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 255:2
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Tidskriftsartikel (refereegranskat)abstract
- Several thousand core-collapse supernovae (CCSNe) of different flavors have been discovered so far. However, identifying their progenitors has remained an outstanding open question in astrophysics. Studies of SN host galaxies have proven to be powerful in providing constraints on the progenitor populations. In this paper, we present all CCSNe detected between 2009 and 2017 by the Palomar Transient Factory. This sample includes 888 SNe of 12 distinct classes out to redshift z approximate to 1. We present the photometric properties of their host galaxies from the far-ultraviolet to the mid-infrared and model the host-galaxy spectral energy distributions to derive physical properties. The galaxy mass function of Type Ic, Ib, IIb, II, and IIn SNe ranges from 10(5) to 10(11.5) M (circle dot), probing the entire mass range of star-forming galaxies down to the least-massive star-forming galaxies known. Moreover, the galaxy mass distributions are consistent with models of star-formation-weighted mass functions. Regular CCSNe are hence direct tracers of star formation. Small but notable differences exist between some of the SN classes. Type Ib/c SNe prefer galaxies with slightly higher masses (i.e., higher metallicities) and star formation rates than Type IIb and II SNe. These differences are less pronounced than previously thought. H-poor superluminous supernovae (SLSNe) and SNe Ic-BL are scarce in galaxies above 10(10) M (circle dot). Their progenitors require environments with metallicities of < 0.4 and < 1 solar, respectively. In addition, the hosts of H-poor SLSNe are dominated by a younger stellar population than all other classes of CCSNe. Our findings corroborate the notion that low metallicity and young age play an important role in the formation of SLSN progenitors.
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| 147. |
- Shpak, Oleksandr, et al.
(författare)
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A Method to Test the Information Quality of Technical Documentation on Websites
- 2014
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Ingår i: 14th International Conference on Quality Software (QSIC). - : IEEE Press. - 9781479971978 ; , s. 296-304
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Konferensbidrag (refereegranskat)abstract
- In software engineering, testing is one of the corner-stones of quality assurance. The idea of software testing can be applied to information quality as well. Technical documentation has a set of intended uses that correspond to use cases in a software system. Documentation is, in many cases, presented via software systems, e.g., web servers and browsers, and contains software, e.g., Javascript for user interaction, animation, and customization, etc. This makes it difficult to find a clear-cut distinction between a software system and technical documentation. However, we can assume that each use case of a technical documentation involves retrieval of some sort of information that helps a user answer a specific questions. To assess information testing as a method, we implemented QAnalytics, a tool to assess the information quality of documentation that is provided by a website. The tool is web-based and allows test managers and site owners to define test cases and success criteria, disseminate the test cases to testers, and to analyze the test results. This way, information testing is easily manageable even for non-technical stakeholders. We applied our testing method and tool in a case study. According to common perception, the website of Linnaeus University needs to be re-engineered. Our method and tool helped the stakeholders identify what information is presented well and which parts of the website that need to change. The test results allowed the design and development effort to prioritize actual quality issues and potentially save time and resources.
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| 148. |
- Sikström, Fredrik, et al.
(författare)
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Evaluation of non-contact methods for joint tracking in a laser beam welding application
- 2016
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Ingår i: The 7th International Swedish Production Symposium, Conference Proceedings. - Lund : Swedish Production Symposium. ; , s. 1-6
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Konferensbidrag (refereegranskat)abstract
- The use of automated laser welding is a key enabler for resource efficient manufacturing in several industrial sectors. One disadvantage with laser welding is the narrow tolerance requirements in the joint fit-up. This is the main reason for the importance of joint tracking systems. This paper describes anevaluation of four non-contact measurement methods to measure the position, gap width and misalignment between superalloy plates. The evaluation was carried out for increased knowledge about the possibilities and limitations with the different methods. The methods are vision-, laser-line-,thermography- and inductive probe systems which are compared in an experimental setup representing a relevant industrial application. Vision is based on a CMOS camera, where the image information is used directly for the measurements. Laser-line is based on triangulation between a camera and a projected laserline. Thermography detects the heat increase in the gap width due to external heat excitation. Inductive probe uses two eddy current coils, and by a complex response method possibilities to narrow gap measurement is achieved. The results, evaluated by comparing the data from the different systems, clearly highlights possibilities and limitations with respective method and serves as a guide in the development of laser beam welding.
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| 149. |
- Stanaway, Jeffrey D., et al.
(författare)
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Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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| 150. |
- Stein, Robert, et al.
(författare)
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Neutrino follow-up with the Zwicky transient facility : results from the first 24 campaigns
- 2023
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 521:4, s. 5046-5063
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Tidskriftsartikel (refereegranskat)abstract
- The Zwicky Transient Facility (ZTF) performs a systematic neutrino follow-up programme, searching for optical counterparts to high-energy neutrinos with dedicated Target-of-Opportunity (ToO) observations. Since first light in March 2018, ZTF has taken prompt observations for 24 high-quality neutrino alerts from the IceCube Neutrino Observatory, with a median latency of 12.2 h from initial neutrino detection. From two of these campaigns, we have already reported tidal disruption event (TDE) AT 2019dsg and likely TDE AT 2019fdr as probable counterparts, suggesting that TDEs contribute >7.8 per cent of the astrophysical neutrino flux. We here present the full results of our programme through to December 2021. No additional candidate neutrino sources were identified by our programme, allowing us to place the first constraints on the underlying optical luminosity function of astrophysical neutrino sources. Transients with optical absolutes magnitudes brighter that -21 can contribute no more than 87 per cent of the total, while transients brighter than -22 can contribute no more than 58 per cent of the total, neglecting the effect of extinction and assuming they follow the star formation rate. These are the first observational constraints on the neutrino emission of bright populations such as superluminous supernovae. None of the neutrinos were coincident with bright optical AGN flares comparable to that observed for TXS 0506+056/IC170922A, with such optical blazar flares producing no more than 26 per cent of the total neutrino flux. We highlight the outlook for electromagnetic neutrino follow-up programmes, including the expected potential for the Rubin Observatory.
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