| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Brinkfeldt, Klas, et al.
(författare)
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Modeling of SiC power modules with double sided cooling
- 2014
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Ingår i: 2014 15th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems, EuroSimE 2014. - : IEEE Computer Society. - 9781479947904
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Konferensbidrag (refereegranskat)abstract
- Silicon Carbide (SiC) based transistor devices have demonstrated higher efficiency switching operation compared to silicon-based, state-of-the-art solutions due to the superior electrical and thermal properties of the SiC material. The improved current density and thermal conductivity allows SiC-based power modules to be smaller than their silicon counterparts for comparable current densities. The active chip area can be reduced further by effectively cooling the devices. In this work, a new power module including SiC bipolar junction transistors (BJT) and diodes and integrated double sided cooling will be introduced. The target application of these modules is a new drive-train system for commercial electric vehicles.
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| 3. |
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| 4. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Lill, Christina M., et al.
(författare)
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The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
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Tidskriftsartikel (refereegranskat)abstract
- A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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| 7. |
- Ruggeri, Kai, et al.
(författare)
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The globalizability of temporal discounting
- 2022
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 6:10, s. 1386-1397
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Tidskriftsartikel (refereegranskat)abstract
- Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns. Ruggeri et al. find in a study of 61 countries that temporal discounting patterns are globally generalizable. Worse financial environments, greater inequality and high inflation are associated with extreme or inconsistent long-term decisions.
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| 8. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 9. |
- Andersson, Dag, et al.
(författare)
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COSIVU - Compact, smart and reliable drive unit for fully electric vehicles
- 2016
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Ingår i: 2016 Pan Pacific Microelectronics Symposium (Pan Pacific). - : Institute of Electrical and Electronics Engineers Inc.. - 9780988887398
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Konferensbidrag (refereegranskat)abstract
- COSIVU is a three year collaborative research project that ended in September 2015 and which has been funded within the European Green Car Initiative (now the European Green Vehicle Initiative). COSIVU addresses one of the most critical technical parts in fully electrical vehicles (FEV) besides the energy storage system: the mechatronic drive-train unit. The COSIVU project has delivered a new system architecture for multiple wheel drive-trains by a smart, compact and durable single-wheel drive unit with integrated electric motor, full silicon carbide (SiC) power electronics (switches and diodes), a novel control and health monitoring module with wireless communication, and an advanced ultra-compact cooling solution. DfR utilizing FEM simulations ensures first time right solutions. This paper presents the main results including the architecture of the drive train solution as well as the modular design of the inverter based on Inverter Building Blocks, one per phase. Performance tests are presented here for the first time for both the heavy duty commercial vehicle solution performed in a test rig by Volvo, and the tests of the COSIVU solution adapted to a passenger car done by Elaphe.
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| 10. |
- 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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| 11. |
- Brenner, David, et al.
(författare)
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Hot-spot KIF5A mutations cause familial ALS
- 2018
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 141, s. 688-697
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de novo frame-shift mutations in the C-terminal domain of KIF5A are associated with neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings, together with the observation that many of the disease genes associated with amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular transport, led us to hypothesize that mutations in KIF5A are also a cause of amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare variant analysis of 426 patients with familial amyotrophic lateral sclerosis and 6137 control subjects, we detected an enrichment of KIF5A splice-site mutations in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 x 10-3), both located in a hot-spot in the C-terminus of the protein and predicted to affect splicing exon 27. We additionally show co-segregation with amyotrophic lateral sclerosis of two canonical splice-site mutations in two families. Investigation of lymphoblast cell lines from patients with KIF5A splice-site mutations revealed the loss of mutant RNA expression and suggested haploinsufficiency as the most probable underlying molecular mechanism. Furthermore, mRNA sequencing of a rare non-synonymous missense mutation (predicting p. Arg1007Gly) located in the C-terminus of the protein shortly upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA splicing in respective patient-derived cell lines owing to abrogation of the donor site. Finally, the non-synonymous single nucleotide variant rs113247976 (minor allele frequency = 1.00% in controls, n = 6137), also located in the C-terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%; P = 1.28 x 10-7). Our study demonstrates that mutations located specifically in a C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis phenotype, and underline the involvement of intracellular transport processes in amyotrophic lateral sclerosis pathogenesis.
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| 12. |
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| 13. |
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| 14. |
- Brinkfeldt, Klas, et al.
(författare)
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Design and Fabrication of a SiC-Based Power Module with Double-Sided Cooling for Automotive Applications
- 2016
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Ingår i: Lecture Notes in Mobility. - Cham : Springer International Publishing. - 2196-5544 .- 2196-5552. ; , s. 157-171, s. 157-172
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The electrification of drive trains combined with special requirements of the automotive and heavy construction equipment applications drives the development of small, highly integrated and reliable power inverters. To minimize the volume and increase the reliability of the power switching devices a module consisting of SiC devices with double sided cooling capability has been developed. There are several benefits related to cooling the power devices on both sides. The major improvement is the ability to increase the power density, and thereby reduce the number of active switching devices required which in turn reduces costs. Other expected benefits of more efficient cooling are reductions in volume and mass per power ratio. Alternatively, improved reliability margins due to lower temperature swings during operation are can be expected. Removing the wire bonds on the top side of the devices is expected to improve the reliability regardless, since wire bonds are known to be one of the main limitations in power switching devices. In addition, it is possible to design the package with substantially lower inductance, which can allow faster switching of the devices. In this paper the design, simulations and fabrication process of a double sided SiC-based power module are presented.
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| 15. |
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| 16. |
- 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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| 17. |
- Brinkfeldt, Klas, et al.
(författare)
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Thermo-Mechanical Simulations of SiC Power Modules with Single and Double Sided Cooling
- 2015
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Ingår i: 16th International Conference on Thermal, Mechanical and Multi-Physics Simulation and Experiments in Microelectronics and Microsystems (EuroSimE), 2015. - : Institute of Electrical and Electronics Engineers Inc.. - 9781479999491 - 9781479999507 ; , s. 1 - 7
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Konferensbidrag (refereegranskat)abstract
- Effectively removing dissipated heat from the switching devices enables a higher current carrying capability per chip area ratio, thus leading to smaller or fewer devices for a given power requirement specification. Further, the use of SiC based devices has proven to increase the efficiency of the system thereby reducing the dissipated heat. Thermal models have been used to compare SiC power modules. Single and double sided cooling have been simulated. The simulated maximum temperatures were 141 °C for the single sided version and 119.7 °C for the double sided version. In addition, the reliability of a single sided module and thermally induced plastic strains of a double sided module have been investigated. A local model of the wire bond interface to the transistor metallization shows a 30/00 maximum increase in plastic strain during the power cycle. Simulations of the creep strain rates in the die attach solder layer for a power cycling loads also shows a 30/00 increase in creep strain per cycle.
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| 18. |
- Brunnsåker, Daniel, 1992, et al.
(författare)
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High-throughput metabolomics for the design and validation of a diauxic shift model
- 2023
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Ingår i: NPJ systems biology and applications. - : Springer Nature. - 2056-7189. ; 9:1, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is a very well studied organism, yet ∼20% of its proteins remain poorly characterized. Moreover, recent studies seem to indicate that the pace of functional discovery is slow. Previous work has implied that the most probable path forward is via not only automation but fully autonomous systems in which active learning is applied to guide high-throughput experimentation. Development of tools and methods for these types of systems is of paramount importance. In this study we use constrained dynamical flux balance analysis (dFBA) to select ten regulatory deletant strains that are likely to have previously unexplored connections to the diauxic shift. We then analyzed these deletant strains using untargeted metabolomics, generating profiles which were then subsequently investigated to better understand the consequences of the gene deletions in the metabolic reconfiguration of the diauxic shift. We show that metabolic profiles can be utilised to not only gaining insight into cellular transformations such as the diauxic shift, but also on regulatory roles and biological consequences of regulatory gene deletion. We also conclude that untargeted metabolomics is a useful tool for guidance in high-throughput model improvement, and is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of genes. Moreover, it is well-suited for automated approaches due to relative simplicity of processing and the potential to make massively high-throughput.
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| 19. |
- Bussy, Aurélie, et al.
(författare)
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Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
- 2023
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 44:7, s. 2684-2700
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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| 20. |
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| 21. |
- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 22. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 23. |
- Festari, Cristina, et al.
(författare)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 24. |
- Freischmidt, Axel, et al.
(författare)
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Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia
- 2015
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 18:5, s. 631-
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative syndrome hallmarked by adult-onset loss of motor neurons. We performed exome sequencing of 252 familial ALS (fALS) and 827 control individuals. Gene-based rare variant analysis identified an exome-wide significant enrichment of eight loss-of-function (LoF) mutations in TBK1 (encoding TANK-binding kinase 1) in 13 fALS pedigrees. No enrichment of LoF mutations was observed in a targeted mutation screen of 1,010 sporadic ALS and 650 additional control individuals. Linkage analysis in four families gave an aggregate LOD score of 4.6. In vitro experiments confirmed the loss of expression of TBK1 LoF mutant alleles, or loss of interaction of the C-terminal TBK1 coiled-coil domain (CCD2) mutants with the TBK1 adaptor protein optineurin, which has been shown to be involved in ALS pathogenesis. We conclude that haploinsufficiency of TBK1 causes ALS and fronto-temporal dementia.
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| 25. |
- Freischmidt, Axel, et al.
(författare)
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Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
- 2014
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 137:11, s. 2938-2950
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
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| 26. |
- Frisoni, Giovanni B., et al.
(författare)
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European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
- 2024
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 23:3, s. 302-312
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Forskningsöversikt (refereegranskat)abstract
- The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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| 27. |
- 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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| 28. |
- Honk, Ludwig, et al.
(författare)
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Longitudinal associations between psychedelic use and psychotic symptoms in the United States and the United Kingdom
- 2024
-
Ingår i: Journal of Affective Disorders. - 0165-0327 .- 1573-2517. ; 351, s. 194-201
-
Tidskriftsartikel (refereegranskat)abstract
- It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology.
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| 29. |
- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 30. |
- Jungclaus, Johann H., et al.
(författare)
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The PMIP4 contribution to CMIP6 - Part 3 : The last millennium, scientific objective, and experimental design for the PMIP4 past1000 simulations
- 2017
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:11, s. 4005-4033
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Tidskriftsartikel (refereegranskat)abstract
- The pre-industrial millennium is among the periods selected by the Paleoclimate Model Intercomparison Project (PMIP) for experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6) and the fourth phase of the PMIP (PMIP4). The past1000 transient simulations serve to investigate the response to (mainly) natural forcing under background conditions not too different from today, and to discriminate between forced and internally generated variability on interannual to centennial timescales. This paper describes the motivation and the experimental set-ups for the PMIP4-CMIP6 past1000 simulations, and discusses the forcing agents orbital, solar, volcanic, and land use/land cover changes, and variations in greenhouse gas concentrations. The past1000 simulations covering the pre-industrial millennium from 850 Common Era (CE) to 1849 CE have to be complemented by historical simulations (1850 to 2014 CE) following the CMIP6 protocol. The external forcings for the past1000 experiments have been adapted to provide a seamless transition across these time periods. Protocols for the past1000 simulations have been divided into three tiers. A default forcing data set has been defined for the Tier 1 (the CMIP6 past1000) experiment. However, the PMIP community has maintained the flexibility to conduct coordinated sensitivity experiments to explore uncertainty in forcing reconstructions as well as parameter uncertainty in dedicated Tier 2 simulations. Additional experiments (Tier 3) are defined to foster collaborative model experiments focusing on the early instrumental period and to extend the temporal range and the scope of the simulations. This paper outlines current and future research foci and common analyses for collaborative work between the PMIP and the observational communities (reconstructions, instrumental data).
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| 31. |
- Kmezik, Cathleen, 1991, et al.
(författare)
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A polysaccharide utilization locus from the gut bacterium Dysgonomonas mossii encodes functionally distinct carbohydrate esterases.
- 2021
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Ingår i: The Journal of biological chemistry. - : Elsevier BV. - 1083-351X .- 0021-9258. ; 296
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota plays a central role in human health by enzymatically degrading dietary fiber and concomitantly excreting short chain fatty acids that are associated with manifold health benefits. The polysaccharide xylan is abundant in dietary fiber but non-carbohydrate decorations hinder efficient cleavage by glycoside hydrolases (GHs) and need to be addressed by carbohydrate esterases (CEs). Enzymes from carbohydrate esterase families 1 and 6 (CE1 & 6) perform key roles in xylan degradation by removing feruloyl and acetate decorations, yet little is known about these enzyme families especially with regards to their diversity in activity. Bacteroidetes bacteria are dominant members of the microbiota and often encode their carbohydrate-active enzymes in multi-gene polysaccharide utilization loci (PULs). Here we present the characterization of three CEs found in a PUL encoded by the gut Bacteroidete Dysgonomonas mossii. We demonstrate that the CEs are functionally distinct, with one highly efficient CE6 acetyl esterase and two CE1 enzymes with feruloyl esterase activities. One multidomain CE1 enzyme contains two CE1 domains: an N-terminal domain feruloyl esterase, and a C-terminal domain with minimal activity on model substrates. We present the structure of the C-terminal CE1 domain with the carbohydrate binding module that bridges the two CE1 domains, as well as a complex of the same protein fragment with methyl ferulate. The investment of D. mossii in producing multiple CEs suggests that improved accessibility of xylan for GHs as well as cleavage of covalent polysaccharide-polysaccharide and lignin-polysaccharide bonds are important enzyme activities in the gut environment.
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| 32. |
- Lewczuk, Piotr, et al.
(författare)
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.
- 2018
-
Ingår i: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. - : Informa UK Limited. - 1814-1412. ; 19:4, s. 244-328
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Tidskriftsartikel (refereegranskat)abstract
- In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.
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| 33. |
- Linnemann, Christoph, et al.
(författare)
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NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study
- 2024
-
Ingår i: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - 0022-3050 .- 1468-330X.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundBlood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites.MethodsComparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72, GRN or MAPT; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer.ResultsNfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12 +/- 1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model.ConclusionsOur results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.
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| 34. |
- Lu, Zhonghai, et al.
(författare)
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RUL Estimation for Power Electronic Devices Based on LESIT Equation
- 2023
-
Ingår i: 2023 PROGNOSTICS AND HEALTH MANAGEMENT CONFERENCE, PHM. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 47-54
-
Konferensbidrag (refereegranskat)abstract
- The LESIT equation is a well-known model to estimate the lifetime of power electronic devices. However, the equation is a static lifetime model that can estimate the total lifetime but not the dynamic lifetime over time and the Remaining Useful Lifetime (RUL), because the equation is not related to time or cycle count. In the paper, we first introduce the concept of dynamic lifetime, i.e., lifetime over time, and include time into the equation to allow it to calculate dynamic lifetime, and then propose a simple equation to conduct the RUL estimation assuming linear damage accumulation. In our experiments using aggregated aging tests, we show that the proposed RUL estimation method can fully capture the general linear decreasing trend of RUL, and in most cases, it gives very accurate estimates, where the deviation depends on the accuracy of the original LESIT estimation.
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| 35. |
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| 36. |
- Lundgren, Peter, et al.
(författare)
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Field torso-warming modalities : a comparative study using a human model
- 2009
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Ingår i: Prehospital Emergency Care. - : Informa Healthcare. - 1090-3127 .- 1545-0066. ; 13:3, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare four field-appropriate torso warming modalities, that do not require AC electrical power, using a human model of non-shivering hypothermia. Methods: Five subjects, serving as their own controls, were cooled four times in 8ºC water, for 10-30 minutes. Shivering was inhibited by Buspirone (30 mg) taken orally prior to cooling and IV Meperidine (1.25 mg/kg) at the end of immersion. Subjects were hoisted out of the water, dried, insulated and then underwent 120 min of either: spontaneous warming only; a charcoal heater on the chest; two flexible hot water bags (total4 liters of water at55°C, replenished every 20 minutes) applied to the chest and upper back; or two chemical heat pads applied to the chest and upper back. Supplemental meperidine (maximum cumulative dose of 3.5 mg/kg) was administered as required to inhibit shivering. Results: Post-cooling afterdrop was compared to spontaneous warming (2.2°C) less for chemical heat pads (1.5°C) and hot water bags (1.6°C, p < 0.05), and was1.8°C with the charcoal heater. Subsequent core rewarming rates, the hot water bags (0.7°C/h) and the charcoal heater (0.6°C/h), tended to be higher than chemical heat pads (0.2°C/h, p = 0.055) and was significantly greater than spontaneous warming (0.1°C/h, p < 0.05). Conclusion: In subjects with shivering suppressed, greater sources of external heat were effective in attenuating core temperature afterdrop whereas sustained sources of external heat effectively established core rewarming. Depending on scenario and available resources, we advice to use charcoal heaters, chemical heat pads or hot water bags as effective means for treating cold patients in the field or during transport to definitive care.
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| 37. |
- Mueller, Kathrin, et al.
(författare)
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Comprehensive analysis of the mutation spectrum in 301 German ALS families
- 2018
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 89:8, s. 817-827
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Recent advances in amyotrophic lateral sclerosis (ALS) genetics have revealed that mutations in any of more than 25 genes can cause ALS, mostly as an autosomal-dominant Mendelian trait. Detailed knowledge about the genetic architecture of ALS in a specific population will be important for genetic counselling but also for genotype-specific therapeutic interventions.Methods Here we combined fragment length analysis, repeat-primed PCR, Southern blotting, Sanger sequencing and whole exome sequencing to obtain a comprehensive profile of genetic variants in ALS disease genes in 301 German pedigrees with familial ALS. We report C9orf72 mutations as well as variants in consensus splice sites and non-synonymous variants in protein-coding regions of ALS genes. We furthermore estimate their pathogenicity by taking into account type and frequency of the respective variant as well as segregation within the families.Results 49% of our German ALS families carried a likely pathogenic variant in at least one of the earlier identified ALS genes. In 45% of the ALS families, likely pathogenic variants were detected in C9orf72, SOD1, FUS, TARDBP or TBK1, whereas the relative contribution of the other ALS genes in this familial ALS cohort was 4%. We identified several previously unreported rare variants and demonstrated the absence of likely pathogenic variants in some of the recently described ALS disease genes.Conclusions We here present a comprehensive genetic characterisation of German familial ALS. The present findings are of importance for genetic counselling in clinical practice, for molecular research and for the design of diagnostic gene panels or genotype-specific therapeutic interventions in Europe.
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| 38. |
- Oeckl, Patrick, et al.
(författare)
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Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase
- 2019
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 90:1, s. 4-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.Methods: The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.Results: CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).Conclusion: Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.
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| 39. |
- Otto, Annika, et al.
(författare)
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Between pace-making and pace-taking : Urban cycle logistics in an accelerated polity
- 2023
-
Ingår i: Cities. - : Elsevier. - 0264-2751 .- 1873-6084. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to explore the concept of social acceleration by examining how cities are trying to speed up, maintain or slow down the pace of societal change. Through studies of cycle logistics policies and actions in cities in Denmark, Norway, the UK, the Netherlands, and Germany, we show how these balance between acting as pace-makers and pace-takers, as well as what the consequences of this balancing act are for enacting cycle logistics. By using acceleration as an overall theoretical concept, we show how transport planners, mobility policy advisors, and digitalization and innovation strategists understand and position themselves when setting the pace for cycle logistics as part of a broader transition toward sustainable transport. We conclude by discussing the implications of this for the general understanding of acceleration in transformations to urban sustainability.
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| 40. |
- Otto, Alexander, et al.
(författare)
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Reliability investigation on SiC BJT power module
- 2016
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Ingår i: PCIM Europe 2016. - : Institute of Electrical and Electronics Engineers Inc.. - 9783800741861 ; , s. 1063-1071
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Konferensbidrag (refereegranskat)abstract
- In this paper reliability investigation results for a power module fully based on silicon carbide (SiC) devices are presented. The module comprises four SiC bipolar junction transistors (BJT) and four SiC diodes in half-bridge configuration and is part of a newly developed 3-phase inverter for construction vehicles as well as for passenger car applications. The reliability investigations include electro-thermal and thermo-mechanical finite element simulations as well as power cycling tests with subsequent failure analyses. Furthermore, a double-sided cooling approach for the SiC BJT power module will be described and its thermal performance compared to the single-sided cooling version.
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| 41. |
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| 42. |
- Otto, Mathias, et al.
(författare)
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2011 IEEE Visualization Contest Winner: Visualizing Unsteady Vortical Behavior of a Centrifugal Pump
- 2012
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Ingår i: IEEE Computer Graphics and Applications. - Providence, USA : Institute of Electrical and Electronics Engineers (IEEE). - 0272-1716 .- 1558-1756. ; 32:5, s. 12-19
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Tidskriftsartikel (refereegranskat)abstract
- In the 2011 IEEE Visualization Contest, the dataset represented a high-resolution simulation of a centrifugal pump operating below optimal speed. The goal was to find suitable visualization techniques to identify regions of rotating stall that impede the pump's effectiveness. The winning entry split analysis of the pump into three parts based on the pump's functional behavior. It then applied local and integration-based methods to communicate the unsteady flow behavior in different regions of the dataset. This research formed the basis for a comparison of common vortex extractors and more recent methods. In particular, integration-based methods (separation measures, accumulated scalar fields, particle path lines, and advection textures) are well suited to capture the complex time-dependent flow behavior. This video (http://youtu.be/oD7QuabY0oU) shows simulations of unsteady flow in a centrifugal pump.
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| 43. |
- Otto, Markus, et al.
(författare)
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Roadmap and standard operating procedures for biobanking and discovery of neurochemical markers in ALS
- 2012
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Ingår i: Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders. - : Informa UK Limited. - 1466-0822 .- 1743-4483. ; 13:1, s. 1-10
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Forskningsöversikt (refereegranskat)abstract
- Despite major advances in deciphering the neuropathological hallmarks of amyotrophic lateral sclerosis (ALS), validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis, defining prognosis and unlocking key pathophysiological pathways are lacking. Although several candidate biomarkers exist, translation into clinical application is hindered by small sample numbers, especially longitudinal, for independent verification. This review considers the potential routes to the discovery of neurochemical markers in ALS, and provides a consensus statement on standard operating procedures that will facilitate multicenter collaboration, validation and ultimately clinical translation.
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| 44. |
- Otto, Mathias, et al.
(författare)
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Visualizing Dynamic Flow Transport of a Centrifugal Pump
- 2012
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Konferensbidrag (refereegranskat)abstract
- In this work we present our results for applying specially designed time-dependent flow visualization methods to a simulation of a centrifugal pump. The simulation has been performed on a high-resolution grid (Figure 1) for 80 time steps using three turbulence methods (SAS, DES, SST [1]) with special focus on the analysis of the so called rotational stall phenomenon. This causes large areas of recirculation and significantly affects the efficiency and life time of the device. We provide a comparative visual analysis using common local vortex detectors as λ2 and the Q criterion, and recent local methods as Sujudi & Haimes [2], and cores of swirling particle motion [3]. Local methods are shown to be insufficient to represent the functional impact and structural importance of the relevant features over time. To efficiently visualize stall cells we applied a set of global and time-dependent measures to convey size, spatial structure and temporal evolution of important transport effects and large-scale turbulent flow structures. Our analysis provides qualitative statements about the application of Lagrangian methods as FTLE [4], integral pressure, arc length of path lines and texture advection (Figure 1) revealing recirculation zones and blocked channels
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| 45. |
- Otto, Mathias, et al.
(författare)
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Visuelle Analysemethoden für das Durchströmungsverhalten einer zentrifugalen Pumpe
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Diese Arbeit beschreibt eine visuelle Funktionsanalyse einer zentrifugalen Pumpe (Abb. 1) [1], für welche sowohl etablierte als auch neu entwickelte Visualisierungstechniken eingesetzt werden. Eine solche Pumpe besteht aus einem Einströmbereich, einem Transportbereich, in dem ein Impeller das Fluid beschleunigt und in den Auslass drückt. Von der Pumpe sind drei simulierte Datensätze mit unterschiedlichen Turbolenzmodellen namens Scale-Adaptive Simulation (SAS), Detached Eddy Simulation (DES) und Shear Stress Transport (SST) gegeben. Jeder Datensatz beinhalte 80 Zeitschritte, die einer Umdrehung des Impellers entsprechen. Das zugrunde liegende Gitter besteht aus ca. 6.5 millionen hexahedralen Zellen und 6.7 millionen Datenpunkten.Wichtig für die Funktionsanalyse sind Wirbelablösungen an den Impellerblättern, die zu großen, stabilen Wirbeln führen können, sodass komplette Kanäle des Impellers blockiert werden, einen sogenannten Rotating Stall. Dieses Phänomen beeinträchtigt die Effizienz und die Lebensdauer der Pumpe.
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| 46. |
- Ovaskainen, Otso, et al.
(författare)
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Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA
- 2024
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Ingår i: Scientific Data. - 2052-4463. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
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| 47. |
- Rugbjerg, Peter, 1988, et al.
(författare)
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Short and long-read ultra-deep sequencing profiles emerging heterogeneity across five platform Escherichia coli strains
- 2021
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Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 65, s. 197-206
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Tidskriftsartikel (refereegranskat)abstract
- Reprogramming organisms for large-scale bioproduction counters their evolutionary objectives of fast growth and often leads to mutational collapse of the engineered production pathways during cultivation. Yet, the mutational susceptibility of academic and industrial Escherichia coli bioproduction host strains are poorly understood. In this study, we apply 2nd and 3rd generation deep sequencing to profile simultaneous modes of genetic heterogeneity that decimate engineered biosynthetic production in five popular E. coli hosts BL21(DE3), TOP10, MG1655, W, and W3110 producing 2,3-butanediol and mevalonic acid. Combining short-read and longread sequencing, we detect strain and sequence-specific mutational modes including single nucleotide polymorphism, inversion, and mobile element transposition, as well as complex structural variations that disrupt the integrity of the engineered biosynthetic pathway. Our analysis suggests that organism engineers should avoid chassis strains hosting active insertion sequence (IS) subfamilies such as IS1 and IS10 present in popular E. coli TOP10. We also recommend monitoring for increased mutagenicity in the pathway transcription initiation regions and recombinogenic repeats. Together, short and long sequencing reads identified latent low-frequency mutation events such as a short detrimental inversion within a pathway gene, driven by 8-bp short inverted repeats. This demonstrates the power of combining ultra-deep DNA sequencing technologies to profile genetic heterogeneities of engineered constructs and explore the markedly different mutational landscapes of common E. coli host strains. The observed multitude of evolving variants underlines the usefulness of early mutational profiling for new synthetic pathways designed to sustain in organisms over long cultivation scales.
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| 48. |
- Schwiegelshohn, Uwe, et al.
(författare)
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Perspectives on grid computing
- 2010
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Ingår i: Future generations computer systems. - : Elsevier BV. - 0167-739X .- 1872-7115. ; 26:8, s. 1104-1115
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Tidskriftsartikel (refereegranskat)abstract
- Grid computing has been the subject of many large national and international IT projects. However, not all goals of these projects have been achieved. In particular. the number of users lags behind the initial forecasts laid out by proponents of grid technologies. This underachievement may have led to claims that the grid concept as a whole is on its way to being replaced by Cloud computing and various X-as-a-Service approaches. In this paper, we try to analyze the current situation and to identify promising directions for future grid development. Although there are shortcomings in current grid systems, we are convinced that the concept as a whole remains valid and can benefit from new developments, including Cloud computing. Furthermore, we strongly believe that some future applications will require the grid approach and that, as a result, further research is required in order to turn this concept into reliable, efficient and user-friendly computing platforms. (c) 2010 Elsevier B.V. All rights reserved.
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| 49. |
- Sogorb-Esteve, Aitana, et al.
(författare)
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Differential impairment of cerebrospinal fluid synaptic biomarkers in the genetic forms of frontotemporal dementia.
- 2022
-
Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Approximately a third of frontotemporal dementia (FTD) is genetic with mutations in three genes accounting for most of the inheritance: C9orf72, GRN, and MAPT. Impaired synaptic health is a common mechanism in all three genetic variants, so developing fluid biomarkers of this process could be useful as a readout of cellular dysfunction within therapeutic trials.A total of 193 cerebrospinal fluid (CSF) samples from the GENetic FTD Initiative including 77 presymptomatic (31 C9orf72, 23 GRN, 23 MAPT) and 55 symptomatic (26 C9orf72, 17 GRN, 12 MAPT) mutation carriers as well as 61 mutation-negative controls were measured using a microflow LC PRM-MS set-up targeting 15 synaptic proteins: AP-2 complex subunit beta, complexin-2, beta-synuclein, gamma-synuclein, 14-3-3 proteins (eta, epsilon, zeta/delta), neurogranin, Rab GDP dissociation inhibitor alpha (Rab GDI alpha), syntaxin-1B, syntaxin-7, phosphatidylethanolamine-binding protein 1 (PEBP-1), neuronal pentraxin receptor (NPTXR), neuronal pentraxin 1 (NPTX1), and neuronal pentraxin 2 (NPTX2). Mutation carrier groups were compared to each other and to controls using a bootstrapped linear regression model, adjusting for age and sex.CSF levels of eight proteins were increased only in symptomatic MAPT mutation carriers (compared with controls) and not in symptomatic C9orf72 or GRN mutation carriers: beta-synuclein, gamma-synuclein, 14-3-3-eta, neurogranin, Rab GDI alpha, syntaxin-1B, syntaxin-7, and PEBP-1, with three other proteins increased in MAPT mutation carriers compared with the other genetic groups (AP-2 complex subunit beta, complexin-2, and 14-3-3 zeta/delta). In contrast, CSF NPTX1 and NPTX2 levels were affected in all three genetic groups (decreased compared with controls), with NPTXR concentrations being affected in C9orf72 and GRN mutation carriers only (decreased compared with controls). No changes were seen in the CSF levels of these proteins in presymptomatic mutation carriers. Concentrations of the neuronal pentraxins were correlated with brain volumes in the presymptomatic period for the C9orf72 and GRN groups, suggesting that they become abnormal in proximity to symptom onset.Differential synaptic impairment is seen in the genetic forms of FTD, with abnormalities in multiple measures in those with MAPT mutations, but only changes in neuronal pentraxins within the GRN and C9orf72 mutation groups. Such markers may be useful in future trials as measures of synaptic dysfunction, but further work is needed to understand how these markers change throughout the course of the disease.
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