| 1. |
- Nilsson, Hans, et al.
(författare)
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Birth of a comet magnetosphere : A spring of water ions
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6220
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Tidskriftsartikel (refereegranskat)abstract
- The Rosetta mission shall accompany comet 67P/Churyumov-Gerasimenko from a heliocentric distance of >3.6 astronomical units through perihelion passage at 1.25 astronomical units, spanning low and maximum activity levels. Initially, the solar wind permeates the thin comet atmosphere formed from sublimation, until the size and plasma pressure of the ionized atmosphere define its boundaries: A magnetosphere is born. Using the Rosetta Plasma Consortium ion composition analyzer, we trace the evolution from the first detection of water ions to when the atmosphere begins repelling the solar wind (~3.3 astronomical units), and we report the spatial structure of this early interaction. The near-comet water population comprises accelerated ions (
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| 2. |
- Alalam, Hanna, et al.
(författare)
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A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
- 2020
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Ingår i: mSystems. - 2379-5077. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.
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| 3. |
- Alalam, Hanna, et al.
(författare)
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Conjugation factors controlling F-plasmid antibiotic resistance transmission
- 2018
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Ingår i: BioRxiv. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The rapid horizontal transmission of many antibiotic resistance genes between bacterial host cells on conjugative plasmids is a major cause of the accelerating antibiotic resistance crisis. Preventing understanding and targeting conjugation, there currently are no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation. We introduce a novel experimental framework to screen for conjugation based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high throughput. We then mix the resistance plasmid carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explored chromosomal genes controlling F plasmid donation within E. coli populations, by screening the Keio deletion collection at high replication. We recover all six known chromosomal gene mutants affecting conjugation and identify >50 novel factors, all of which diminish antibiotic resistance transmission. We verify 10 of the novel genes' effects in a liquid mating assay. The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improves the longevity of current and future antibiotics.
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| 4. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 5. |
- Sonesson, Ulf, et al.
(författare)
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Paths to a sustainable food sector: integrated design and LCA of future food supply chains : the case of pork production in Sweden
- 2016
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Ingår i: The International Journal of Life Cycle Assessment. - : Springer Ferlag. - 0948-3349 .- 1614-7502. ; 21:5, s. 664-676
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To describe a more sustainable food sector, a supply chain approach is needed. Changing a supply chain inevitably means that various attributes of the product and its system will change. This project assumed this challenge and delivered detailed descriptions, life cycle assessment (LCA) evaluations, and consequence assessments of the supply chains of six commodities, i.e., milk, cheese, beef, pork, chicken, and bread, from a Swedish region. This paper presents results for the pork supply chain. Methods: In the project setup, experts on production along supply chains designed three scenarios for environmentally improved systems. These scenarios, i.e., the ecosystem, plant nutrients, and climate scenarios, were intended to address different clusters of environmental goals. The next step was to challenge these scenarios by considering their possible consequences for products and systems from the food safety, sensory quality, animal welfare, consumer appreciation, and (for primary production only) cost perspectives. This led to changes in production system design to prevent negative consequences. The final supply chains were quantified using LCA and were again assessed from the three perspectives. Results and discussion: The scenario design approach worked well, thoroughly and credibly describing the production systems. Assessment of consequences bolstered the credibility and quality of the systems and results. The LCA of pig production and smoked ham identified large potentials for improvement by implementing available knowledge: global warming potential (GWP) could be reduced 21–54 % and marine eutrophication by 14–45 %. The main reason for these improvements was improved productivity (approaching the best producers’ current performance), though dedicated measures were also important, resulting in increased nitrogen efficiency, more varied crop rotations for crop production and better production management, and improved animal health and manure management for animal production. Reduced post-farm wastage contributed as did reduced emissions from fertilizer production. Conclusions: The working approach applied was successful in integrating LCA research with food system production expertise to deliver results relevant to supply chain decision-makers. The consequence assessments brought considerable value to the project, giving its results greater credibility. By introducing constraints in the form of “no negative consequences and no increased costs,” the work was “guided” so that the scenario design avoided being hampered by too many opportunities.
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| 6. |
- Arnell, Henrik, et al.
(författare)
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The genetics of primary nocturnal enuresis: inheritance and suggestion of a second major gene on chromosome 12q
- 1997
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 34:5, s. 360-5
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Tidskriftsartikel (refereegranskat)abstract
- Primary nocturnal enuresis (PNE), or bedwetting at night, affects approximately 10% of 6 year old children. Genetic components contribute to the pathogenesis and recently one locus was assigned to chromosome 13q. We evaluated the genetic factors and the pattern of inheritance for PNE in 392 families. Dominant transmission was observed in 43% and an apparent recessive mode of inheritance was observed in 9% of the families. Among the 392 probands the ratio of males to females was 3:1 indicating sex linked or sex influenced factors. Linkage to candidate regions was tested in 16 larger families segregating for autosomal dominant PNE. A gene for PNE was excluded from chromosome 13q in 11 families, whereas linkage to the interval D13S263-D13S291 was suggested (Zmax = 2.1) in three families. Further linkage analyses excluded about 1/3 of the genome at a 10 cM resolution except the region around D12S80 on chromosome 12q that showed a positive two point lod score in six of the families (Zmax = 4.2). This locus remains suggestive because the material was not sufficiently large to give evidence for heterogeneity. Our pedigree analysis indicates that major genes are involved in a large proportion of PNE families and the linkage results suggest that such a gene is located on chromosome 12q.
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| 7. |
- Austrell, Per Erik, et al.
(författare)
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Survey of Design Methods and Material Characteristics in Rubber Engineering
- 1999
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The unique properties of elastomeric materials are taken advantage of in many engineering applications. Elastomeric units are used as couplings or mountings between stiff structures. Examples of these are shock absorbers, vibration insulators, flexible joints, seals and suspensions.The development of computers and of analysis programs in this area has given engineers a new tool for the design of elastomeric components. Computer simulation by finite element analysis has become increasingly important, allowing the mechanical behavior of products with for complex geometries, as well as loading cases of different kinds to be evaluated. Computer simulations enable both static and dynamic aspects to be analyzed. These matters have been recognized by the manufacturers of rubber products and by their customers. The benefits are shorter time for product development and also quality improvements.However, the possibilities available for finding less complicated technical solutions at lower cost with the use of elastomers, has not been fully utilized. Rubber components could be employed more frequently in design if engineers were more familiar with materials of this sort.Part of the problem lies in education and in the dissemination of information. Engineers working in the design area tend to not be very familiar with elastomeric materials and their properties. The offerings of courses on the mechanics of polymers at schools and universities are very limited. Skillful engineers in this field have usually acquired their knowledge through many years of experience and not formal education.Moreover, the complicated nature of the material behavior involved makes it difficult to devise general design rules and design tools. Only recently have computers and analysis programs become powerful enough for the analysis of nonlinear elastic problems involving large strains.It is essential, if one is to become competitive in high-tech applications, to possess a thorough knowledge of computer methods, material models and test methods available.There has likewise been a lack of relevant data for the computer analysis of elastomeric materials. The design tools employed rely on the material models available and on the test data required for the calibration of these models. In many cases, the only information available for analysis is a value for the hardness of the rubber in question. The wide variety of rubber compounds is also a problem. The characterization of different materials is costly and time-consuming. There is thus a need for simple and reliable methods to characterize the different vulcanizates.
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| 8. |
- Bergman, Sofia, 1991-, et al.
(författare)
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Ion bulk speeds and temperatures in the diamagnetic cavity of comet 67P from RPC-ICA measurements
- 2021
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 503:2, s. 2733-2745
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Tidskriftsartikel (refereegranskat)abstract
- Y Comets are constantly interacting with the solar wind. When the comet activity is high enough, this leads to the creation of a magnetic field free region around the nucleus known as the diamagnetic cavity. It has been suggested that the ion-neutral drag force is balancing the magnetic pressure at the cavity boundary, but after the visit of Rosetta to comet 67P/Churyumov-Gerasimenko the coupling between ions and neutrals inside the cavity has been debated, at least for moderately active comets. In this study, we use data from the ion composition analyser to determine the bulk speeds and temperatures of the low-energy ions in the diamagnetic cavity of comet 67P. The low-energy ions are affected by the negative spacecraft potential, and we use the Spacecraft Plasma Interaction Software to model the resulting influence on the detected energy spectra. We find bulk speeds of 5-10 km s(-1) with a most probable speed of 7 km s(-1), significantly above the velocity of the neutral particles. This indicates that the collisional coupling between ions and neutrals is not strong enough to keep the ions at the same speed as the neutrals inside the cavity. The temperatures are in the range 0.7-1.6 eV, with a peak probability at 1.0 eV. We attribute the major part of the temperature to the fact that ions are born at different locations in the coma, and hence are accelerated over different distances before reaching the spacecraft.
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| 9. |
- Bergman, Sofia, 1991-
(författare)
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Low-energy ions around comet 67P/Churyumov-Gerasimenko
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low-energy ions play important roles in the formation of the plasma environment around a comet. Reliable ways of measuring these ions are therefore of high importance to fully understand the processes and dynamics of this environment. Unfortunately, low-energy ions are infamously difficult to detect. A spacecraft interacts with the surrounding environment, which leads to an accumulation of charge on the spacecraft surface. As a result, the surface acquires an electrostatic potential with respect to the surrounding plasma, which can be either positive or negative. Low-energy ions are then attracted to or repelled from the charged surface before being detected by the instrument on board, resulting in an energy shift and change of travel direction of the ions. The Rosetta mission studied comet 67P/Churyumov-Gerasimenko during the years 2014-2016, and provided the most detailed observations of a comet and its environment to date. The Ion Composition Analyzer of the Rosetta Plasma Consortium (RPC-ICA) measured positive ions in the cometary environment with energies down to just a few eV. The low-energy part of the data is, however, difficult to interpret due to the distortions caused by the spacecraft potential. In this thesis, the Spacecraft Plasma Interaction Software (SPIS) is used to correct the low-energy ion measurements made by RPC-ICA for the effects introduced by the spacecraft potential. The distortion of the effective field of view is modelled for different ion energies and plasma environments, and the results are used to correct the flow direction of low-energy ions around the comet. The FOV distortion can be considered insignificant when the energy of the ions (in eV) is twice the value of the spacecraft potential (in volts). The FOV distortion at lower energies is geometry dependent, and varies substantially between different pixels of the instrument. The FOV distortion is furthermore dependent on the Debye length of the surrounding plasma. The knowledge obtained from the simulations is subsequently used to study the flow direction of low-energy ions in and around the diamagnetic cavity, a region where the magnetic field is essentially zero and low-energy ions are important for the dynamics. Evidence of counter-streaming ions are found, with ions flowing both radially away from and back towards the nucleus. SPIS is also used to model the influence of the spacecraft potential on the energy spectrum of the ions, and from this the bulk speed and temperature of the low-energy ions in the diamagnetic cavity were determined to 5-10 km/s and 0.7-1.6 eV, respectively. The bulk speed is significantly above the speed of the neutral particles, indicating a weak coupling between ions and neutrals in the diamagnetic cavity.
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| 10. |
- Bergman, Sofia, 1991-
(författare)
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The effect of spacecraft charging on low-energy ion measurements around comet 67P/Churyumov-Gerasimenko
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A spacecraft in space interacts with the surrounding environment and aqcuires an electrostatic potential. Charged particles are constantly bombarding the surface of the spacecraft, and at the same time solar EUV radiation induces photoemission, causing electrons to be emitted from the surface. The result is a transfer of charge between the environment and the spacecraft surface, and the surface charges to a positive or negative potential. The charged surface can cause interferences with scientific instruments on board. In this thesis, we investigate how spacecraft charging affects low-energy ion measurements. The Rosetta spacecraft visited comet 67P/Churyumov-Gerasimenko between the years 2014-2016. On board the spacecraft, the Ion Composition Analyzer (ICA) was measuring positive ions in the environment around the comet with the aim of investigating the interaction between cometary particles and the solar wind. Important for this interaction is ions with a low energy. Measuring these ions is, however, difficult due to the charged spacecraft surface. Rosetta was commonly charged to a negative potential, and consequently the measured positive ions were accelerated toward the surface before detection, affecting both their energy and travel direction. In this thesis, we study how the changed travel directions affected the effective field of view (FOV) of the instrument. We use the Spacecraft Plasma Interaction Software (SPIS) to simulate the spacecraft plasma interactions and the ion trajectories around the spacecraft. The results show that the FOV of ICA is severely distorted at low ion energies, but the distortion varies between different viewing directions of the instrument and is dependent on the properties of the surrounding plasma.
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