| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Ollila, Hanna M., et al.
(författare)
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Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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| 4. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 5. |
- Aléx, Jonas, et al.
(författare)
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Being cold when injured in a cold environment : patients' experiences
- 2013
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Ingår i: International Emergency Nursing. - : Elsevier BV. - 1755-599X .- 1878-013X. ; 21:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients in prehospital care, irrespective of diseases or trauma might experience thermal discomfort because of a cold environment and are at risk for decreasing body temperature which can increase both morbidity and mortality.Objective: To explore patients' experiences of being cold when injured in a cold environment.Method: Twenty persons who had been injured in a cold environment in northern Sweden were interviewed. Active heat supply was given to 13 of them and seven had passive heat supply. The participants were asked to narrate their individual experience of cold and the pre- and post-injury event, until arrival at the emergency department. The interviews were transcribed verbatim, then analyzed with qualitative content analysis.Results: Patients described that they suffered more from the cold than because of the pain from the injury. Patients who received active heat supply experienced it in a positive way. Two categories were formulated: Enduring suffering and Relief of suffering.Conclusion: Thermal discomfort became the largest problem independent of the severity of the injuries. We recommend the use of active heat supply to reduce the negative experiences of thermal discomfort when a person is injured in a cold environment.
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| 6. |
- Brinkfeldt, Klas, et al.
(författare)
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Thermal Simulations and Experimental Verification of Power Modules Designed for Double Sided Cooling
- 2016
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Ingår i: Electronic Components and Technology. - : Institute of Electrical and Electronics Engineers Inc.. - 0569-5503. ; , s. 1415-1422
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Tidskriftsartikel (refereegranskat)abstract
- Cooling power modules on both sides of the active switching devices reduces the operational junction temperature compared to conventional single sided cooling. In this work, thermal simulations of power modules based on single sided cooling concepts are compared with double sided cooling counterparts. Expected junction temperatures, maximum temperatures and maximum current capability is analyzed. In addition, experimental verification in the form of comparisons with thermal characterization tests for both single-And double sided power modules based on SiC bipolar junction transistors is presented. Results from simulations show that cooling of both sides of the active switching devices can reduce the thermal resistance by more than 40 percent. This number depends on the heat transfer coefficient. From one example, simulating a worst case stall condition of the electric machine, the use of double sided cooling reduces the maximum junction temperature from 167 °C to 106 °C at a load current of 300 A using a heat transfer coefficient of 4 kW/m2K and 4 kHz switching frequency. Furthermore, the temperature decreases to 97°C if AlN-based DBC substrates are used instead of alumina DBCs. Results from the experimental comparison between double-And single sided cooling showed that the maximum temperature for a load current range of 15 A to 50 A was reduced by 18 percent to 55 percent by using double sided cooling. At a device temperature of 60 °C, the increased thermal capability of the double sided version allowed for a 20 A higher load current, which corresponded to operation under 50 percent higher power losses. Double sided cooling also increased the maximum current capability through a single SiC BJT by more than 20 percent beyond the maximum current capability through the single sided cooling version.
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| 7. |
- Hedin, Karl Alex, et al.
(författare)
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Cold Exposure and Oral Delivery of GLP-1R Agonists by an Engineered Probiotic Yeast Strain Have Antiobesity Effects in Mice
- 2023
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Ingår i: ACS Synthetic Biology. - 2161-5063. ; 12:11, s. 3433-3442
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Tidskriftsartikel (refereegranskat)abstract
- Advanced microbiome therapeutics (AMTs) holds promise in utilizing engineered microbes such as bacteria or yeasts for innovative therapeutic applications, including the in situ delivery of therapeutic peptides. Glucagon-like peptide-1 receptor agonists, such as Exendin-4, have emerged as potential treatments for type 2 diabetes and obesity. However, current administration methods face challenges with patient adherence and low oral bioavailability. To address these limitations, researchers are exploring improved oral delivery methods for Exendin-4, including utilizing AMTs. This study engineered the probiotic yeast Saccharomyces boulardii to produce Exendin-4 (Sb-Exe4) in the gastrointestinal tract of male C57BL/6 mice to combat diet-induced obesity. The biological efficiency of Exendin-4 secreted by S. boulardii was analyzed ex vivo on isolated pancreatic islets, demonstrating induced insulin secretion. The in vivo characterization of Sb-Exe4 revealed that when combined with cold exposure (8 °C), the Sb-Exe4 yeast strain successfully suppressed appetite by 25% and promoted a 4-fold higher weight loss. This proof of concept highlights the potential of AMTs to genetically modify S. boulardii for delivering active therapeutic peptides in a precise and targeted manner. Although challenges in efficacy and regulatory approval persist, AMTs may provide a transformative platform for personalized medicine. Further research in AMTs, particularly focusing on probiotic yeasts such as S. boulardii, holds great potential for novel therapeutic possibilities and enhancing treatment outcomes in diverse metabolic disorders.
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| 8. |
- Malmström, Erik, et al.
(författare)
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The Long Non-Coding Antisense RNA JHDM1D-AS1 Regulates Inflammatory Responses in Human Monocytes
- 2022
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Monocytes are key players in innate immunity, with their ability to regulate inflammatory responses and combat invading pathogens. There is a growing body of evidence indicating that long non-coding RNA (lncRNA) participate in various cellular biological processes, including the innate immune response. The immunoregulatory properties of numerous lncRNAs discovered in monocytes remain largely unexplored. Here, by RNA sequencing, we identified a lncRNA JHDM1D-AS1, which was upregulated in blood monocytes obtained from patients with sepsis relative to healthy controls. JHDM1D-AS1 expression was induced in primary human monocytes exposed to Toll-like receptor ligands, such as lipopolysaccharide (LPS), or bacteria. The inducibility of JHDM1D-AS1 expression in monocytes depended, at least in part, on nuclear factor–κB activation. JHDM1D-AS1 knockdown experiments in human monocyte-derived macrophages revealed significantly enhanced expression of inflammatory mediators, before and after exposure to LPS, relative to control cells. Specifically, genes involved in inflammatory responses were upregulated (e.g., CXCL2, CXCL8, IL1RN, TREM1, TNF, and IL6), whereas genes involved in anti-inflammatory pathways were downregulated (e.g., SOCS1 and IL10RA). JHDM1D-AS1 overexpression in a pro-monocytic cell line revealed diminished pro-inflammatory responses subsequent to LPS challenge. Collectively, these findings identify JHDM1D-AS1 as a potential anti-inflammatory mediator induced in response to inflammatory stimuli.
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| 9. |
- Otto, Ilona M., et al.
(författare)
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Social tipping dynamics for stabilizing Earth's climate by 2050
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : The National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:5, s. 2354-2365
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Tidskriftsartikel (refereegranskat)abstract
- Safely achieving the goals of the Paris Climate Agreement requires a worldwide transformation to carbon-neutral societies within the next 30 y. Accelerated technological progress and policy implementations are required to deliver emissions reductions at rates sufficiently fast to avoid crossing dangerous tipping points in the Earth's climate system. Here, we discuss and evaluate the potential of social tipping interventions (STIs) that can activate contagious processes of rapidly spreading technologies, behaviors, social norms, and structural reorganization within their functional domains that we refer to as social tipping elements (STE5). STE5 are subdomains of the planetary socioeconomic system where the required disruptive change may take place and lead to a sufficiently fast reduction in anthropogenic greenhouse gas emissions. The results are based on online expert elicitation, a subsequent expert workshop, and a literature review. The STIs that could trigger the tipping of STE subsystems include 1) removing fossil-fuel subsidies and incentivizing decentralized energy generation (STE1, energy production and storage systems), 2) building carbon-neutral cities (STE2, human settlements), 3) divesting from assets linked to fossil fuels (STE3, financial markets), 4) revealing the moral implications of fossil fuels (STE4, norms and value systems), 5) strengthening climate education and engagement (STE5, education system), and 6) disclosing information on greenhouse gas emissions (STE6, information feedbacks). Our research reveals important areas of focus for larger-scale empirical and modeling efforts to better understand the potentials of harnessing social tipping dynamics for climate change mitigation.
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| 10. |
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| 11. |
- Pontes, Gabriel M., et al.
(författare)
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Drier tropical and subtropical Southern Hemisphere in the mid-Pliocene Warm Period
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Thermodynamic arguments imply that global mean rainfall increases in a warmer atmosphere; however, dynamical effects may result in more significant diversity of regional precipitation change. Here we investigate rainfall changes in the mid-Pliocene Warm Period (similar to 3 Ma), a time when temperatures were 2-3 degrees C warmer than the pre-industrial era, using output from the Pliocene Model Intercomparison Projects phases 1 and 2 and sensitivity climate model experiments. In the Mid-Pliocene simulations, the higher rates of warming in the northern hemisphere create an interhemispheric temperature gradient that enhances the southward cross-equatorial energy flux by up to 48%. This intensified energy flux reorganizes the atmospheric circulation leading to a northward shift of the Inter-Tropical Convergence Zone and a weakened and poleward displaced Southern Hemisphere Subtropical Convergences Zones. These changes result in drier-than-normal Southern Hemisphere tropics and subtropics. The evaluation of the mid-Pliocene adds a constraint to possible future warmer scenarios associated with differing rates of warming between hemispheres.
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| 12. |
- Pontes, Gabriel M., et al.
(författare)
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Mid-Pliocene El Niño/Southern Oscillation suppressed by Pacific intertropical convergence zone shift
- 2022
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15:9, s. 726-734
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Tidskriftsartikel (refereegranskat)abstract
- The El Niño/Southern Oscillation (ENSO), the dominant driver of year-to-year climate variability in the equatorial Pacific Ocean, impacts climate pattern across the globe. However, the response of the ENSO system to past and potential future temperature increases is not fully understood. Here we investigate ENSO variability in the warmer climate of the mid-Pliocene (~3.0–3.3 Ma), when surface temperatures were ~2–3 °C above modern values, in a large ensemble of climate models—the Pliocene Model Intercomparison Project. We show that the ensemble consistently suggests a weakening of ENSO variability, with a mean reduction of 25% (±16%). We further show that shifts in the equatorial Pacific mean state cannot fully explain these changes. Instead, ENSO was suppressed by a series of off-equatorial processes triggered by a northward displacement of the Pacific intertropical convergence zone: weakened convective feedback and intensified Southern Hemisphere circulation, which inhibit various processes that initiate ENSO. The connection between the climatological intertropical convergence zone position and ENSO we find in the past is expected to operate in our warming world with important ramifications for ENSO variability.
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| 13. |
- Schell, Carl Otto, et al.
(författare)
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Essential Emergency and Critical Care : a consensus among global clinical experts.
- 2021
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 6:9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Globally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.METHODS: In a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.RESULTS: The 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.CONCLUSION: The study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide.
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| 14. |
- Abbafati, Cristiana, et al.
(författare)
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- 2020
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Tidskriftsartikel (refereegranskat)
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