| 1. |
- Bremer, Johan, 1991, et al.
(författare)
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Analysis of Lateral Thermal Coupling for GaN MMIC Technologies
- 2018
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 66:10, s. 4430-4438
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a study of the lateral heat propagation in an aluminum gallium nitride/gallium nitride (AlGaN/GaN) heterostructure grown on a silicon carbide substrate. The study is enabled by the design of a temperature sensor that utilizes the temperature-dependent I-V characteristic of a semiconductor resistor, making it suitable for integration in GaN monolithic microwave integrated circuit technologies. Using the sensor, we are able to characterize the thermal transient response and extract lateral thermal time constants from the measurements. Time constants in the range from 25 mu s to 1.2 ms are identified. Furthermore, the heat propagation properties are characterized for heat source-to-sensor distances of 86-484 mu m, resulting in delay times from 3.5 to 111 mu s. It is shown that both the time constants and propagation delay increase with temperature. An empirical model of the sensor current versus temperature and voltage is proposed and used to predict the junction temperature of the sensor. The study provides knowledge for heat management design and proposes an integrated temperature measurement solution for future highly integrated GaN applications.
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| 2. |
- Berglund, Sara, et al.
(författare)
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Cardiorenal function and survival in in-hospital cardiac arrest : A nationwide study of 22,819 cases
- 2022
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 172, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- Background: We studied the association between cardiorenal function and survival, neurological outcome and trends in survival after in-hospital Methods: We included cases aged 18 years in the Swedish Cardiopulmonary Resuscitation Registry during 2008 to 2020. The CKD-EPI equation was used to calculate estimated glomerular filtration rate (eGFR). A history of heart failure was defined according to contemporary guideline criteria. Logistic regression was used to study survival. Neurological outcome was assessed using cerebral performance category (CPC). Results: We studied 22,819 patients with IHCA. The 30-day survival was 19.3%, 16.6%, 22.5%, 28.8%, 39.3%, 44.8% and 38.4% in cases with eGFR < 15, 15-29, 30-44, 45-59, 60-89, 90-130 and 130-150 ml/min/1.73 m2, respectively. All eGFR levels below and above 90 ml/min/1.73 m2 were associated with increased mortality. Probability of survival at 30 days was 62% lower in cases with eGFR < 15 ml/min/1.73 m2, compared with normal kidney function. At every level of eGFR, presence of heart failure increased mortality markedly; patients without heart failure displayed higher mortality only at eGFR below 30 ml/min/1.73 m2. Among survivors with eGFR < 15 ml/min/1.73 m2, good neurological outcome was noted in 87.2%. Survival increased in most groups over time, but most for those with eGFR < 15 ml/min/1.73 m2, and least for those with normal eGFR. Conclusions: All eGFR levels below and above normal range are associated with increased mortality and this association is modified by the presence of heart failure. Neurological outcome is good in the majority of cases, across kidney function levels and survival is increasing.
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| 3. |
- Chen, Yu, 1990, et al.
(författare)
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Reconstruction, simulation and analysis of enzyme-constrained metabolic models using GECKO Toolbox 3.0
- 2024
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Ingår i: Nature Protocols. - 1754-2189 .- 1750-2799. ; 19:3, s. 629-667
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are computational representations that enable mathematical exploration of metabolic behaviors within cellular and environmental constraints. Despite their wide usage in biotechnology, biomedicine and fundamental studies, there are many phenotypes that GEMs are unable to correctly predict. GECKO is a method to improve the predictive power of a GEM by incorporating enzymatic constraints using kinetic and omics data. GECKO has enabled reconstruction of enzyme-constrained metabolic models (ecModels) for diverse organisms, which show better predictive performance than conventional GEMs. In this protocol, we describe how to use the latest version GECKO 3.0; the procedure has five stages: (1) expansion from a starting metabolic model to an ecModel structure, (2) integration of enzyme turnover numbers into the ecModel structure, (3) model tuning, (4) integration of proteomics data into the ecModel and (5) simulation and analysis of ecModels. GECKO 3.0 incorporates deep learning-predicted enzyme kinetics, paving the way for improved metabolic models for virtually any organism and cell line in the absence of experimental data. The time of running the whole protocol is organism dependent, e.g., ~5 h for yeast.
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| 4. |
- Dejby, Ellen, et al.
(författare)
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Left-sided valvular heart disease and survival in out-of-hospital cardiac arrest: a nationwide registry-based study.
- 2023
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Ingår i: Scientific reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Survival in left-sided valvular heart disease (VHD; aortic stenosis [AS], aortic regurgitation [AR], mitral stenosis [MS], mitral regurgitation [MR]) in out-of-hospital cardiac arrest (OHCA) is unknown. We studied all cases of OHCA in the Swedish Registry for Cardiopulmonary Resuscitation. All degrees of VHD, diagnosed prior to OHCA, were included. Association between VHD and survival was studied using logistic regression, gradient boosting and Cox regression. We studied time to cardiac arrest, comorbidities, survival, and cerebral performance category (CPC) score. We included 55,615 patients; 1948 with AS (3,5%), 384 AR (0,7%), 17 MS (0,03%), and 704 with MR (1,3%). Patients with MS were not described due to low case number. Time from VHD diagnosis to cardiac arrest was 3.7years in AS, 4.5years in AR and 4.1years in MR. ROSC occurred in 28% with AS, 33% with AR, 36% with MR and 35% without VHD. Survival at 30days was 5.2%, 10.4%, 9.2%, 11.4% in AS, AR, MR and without VHD, respectively. There were no survivors in people with AS presenting with asystole or PEA. CPC scores did not differ in those with VHD compared with no VHD. Odds ratio (OR) for MR and AR showed no difference in survival, while AS displayed OR 0.58 (95% CI 0.46-0.72), vs no VHD. AS is associated with halved survival in OHCA, while AR and MR do not affect survival. Survivors with AS have neurological outcomes comparable to patients without VHD.
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| 5. |
- Gustafsson, Johan, 1991-
(författare)
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Exposure and effects of naturally produced hydroxylated polybrominated diphenyl ethers in fish : Implications for Baltic Sea wildlife
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate if naturally produced hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are causing negative health effects for Baltic Sea wildlife. In the laboratory, OH-PBDEs have shown to be potent disrupters of energy metabolism as well as endocrine disruptors and neurotoxins. OH-PBDEs are naturally produced, for example, by filamentous macroalgae in the Baltic Sea but are also metabolites of the flame retardants polybrominated diphenyl ethers (PBDEs). High concentrations of OH-PBDEs have been detected in several species in the Baltic Sea, including the European perch (Perca fluviatilis). The concentrations of OH-PBDEs in perch, and some other species from the Baltic Sea, are within reported toxicological effect concentrations.In this thesis, perch were sampled approximately once a week during an exposure peak of OH-PBDEs between May and October in 2018. In Paper I, correlations between OH-PBDEs and several health biomarkers in perch were studied. A higher OH-PBDE concentration correlated with increased ethoxyresorufin-O-deethylase (EROD) activity, increased plasma lactate concentration, increased plasma glucose concentration, decreased lipid percentage in muscle, and decreased liver somatic index. These correlations indicate that OH-PBDEs might cause negative health effects in perch from the Baltic Sea.Many aquatic species in the Baltic Sea have been reported to suffer from thiamine (vitamin B1) deficiency. Thiamine deficiency could be a confounding factor when assessing potential in vivo effects of OH-PBDEs. Hence, in Paper II, the thiamine status of perch was investigated. Perch were found to have sufficient thiamine, thus thiamine deficiency is not a confounding factor when assessing potential effects of OH-PBDEs in perch from the Baltic Sea.In Paper III, metabolomics was performed on zebrafish (Danio rerio) embryos exposed to OH-PBDEs. The aim was to study the toxicity of OH-PBDEs at the metabolome level and to identify selective and sensitive biomarker(s) for energy disruption of OH-PBDEs. OH-PBDEs were found to cause diverse metabolic effects at environmentally relevant concentrations. Accumulation of succinic acid, a key metabolite for energy production and regulation of the immune system, was suggested as a potential biomarker for energy disruption due to OH-PBDEs. In Paper IV, lipids and 19 polar metabolites, including metabolites observed to be affected by OH-PBDEs in Paper III, were analysed in perch from the Baltic Sea. Among other findings, a correlation between increased OH-PBDE exposure and increased concentration of succinic acid was observed. The correlations observed in the perch to a large extent agreed with the metabolic effects seen in zebrafish embryos exposed to OH-PBDEs (Paper III), indicating potential causality between exposure to OH-PBDEs and effects in perch from the Baltic Sea.The correlations observed in this thesis between OH-PBDEs and biomarkers in perch should be interpreted with caution as the correlations could be spurious, for example caused by underlying environmental factors. However, taken together, the results support the hypothesis that naturally produced OH-PBDEs could cause negative health effects in perch from the Baltic Sea.
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| 6. |
- Hjort, Filip, 1991, et al.
(författare)
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Optical microprism cavities based on dislocation-free GaN
- 2020
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 117:23
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional growth of nanostructures can be used to reduce the threading dislocation density that degrades III-nitride laser performance. Here, nanowire-based hexagonal GaN microprisms with flat top and bottom c-facets are embedded between two dielectric distributed Bragg reflectors to create dislocation-free vertical optical cavities. The cavities are electron beam pumped, and the quality (Q) factor is deduced from the cavity-filtered yellow luminescence. The Q factor is similar to 500 for a 1000nm wide prism cavity and only similar to 60 for a 600nm wide cavity, showing the strong decrease in Q factor when diffraction losses become dominant. Measured Q factors are in good agreement with those obtained from quasi-3D finite element frequency-domain method and 3D beam propagation method simulations. Simulations further predict that a prism cavity with a 1000nm width will have a Q factor of around 2000 in the blue spectral regime, which would be the target regime for real devices. These results demonstrate the potential of GaN prisms as a scalable platform for realizing small footprint lasers with low threshold currents.
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| 7. |
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| 8. |
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| 9. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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| 10. |
- Otto, Maximilian, 1991, et al.
(författare)
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Expansion of the Yeast Modular Cloning Toolkit for CRISPR-Based Applications, Genomic Integrations and Combinatorial Libraries
- 2021
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Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 10:12, s. 3461-3474
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Tidskriftsartikel (refereegranskat)abstract
- Standardisation of genetic parts has become a topic of increasing interest over the last decades. The promise of simplifying molecular cloning procedures, while at the same time making them more predictable and reproducible has led to the design of several biological standards, one of which is modular cloning (MoClo). The Yeast MoClo toolkit provides a large library of characterised genetic parts combined with a comprehensive and flexible assembly strategy. Here we aimed to (1) simplify the adoption of the standard by providing a simple design tool for including new parts in the MoClo library, (2) characterise the toolkit further by demonstrating the impact of a BglII site in promoter parts on protein expression, and (3) expand the toolkit to enable efficient construction of gRNA arrays, marker-less integration cassettes and combinatorial libraries. These additions make the toolkit more applicable for common engineering tasks and will further promote its adoption in the yeast biological engineering community.
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