| 1. |
- Tesi, Bianca, et al.
(författare)
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Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms
- 2017
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:16, s. 2266-2279
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Tidskriftsartikel (refereegranskat)abstract
- Several monogenic causes of familial myelodysplastic syndrome (MDS) have recently been identified. We studied 2 families with cytopenia, predisposition to MDS with chromosome 7 aberrations, immunodeficiency, and progressive cerebellar dysfunction. Genetic studies uncovered heterozygous missense mutations in SAMD9L, a tumor suppressor gene located on chromosome arm 7q. Consistent with a gain-of-function effect, ectopic expression of the 2 identified SAMD9L mutants decreased cell proliferation relative to wild-type protein. Of the 10 individuals identified who were heterozygous for either SAMD9L mutation, 3 developed MDS upon loss of the mutated SAMD9L allele following intracellular infections associated with myeloid, B-, and natural killer (NK)-cell deficiency. Five other individuals, 3 with spontaneously resolved cytopenic episodes in infancy, harbored hematopoietic revertant mosaicism by uniparental disomy of 7q, with loss of the mutated allele or additional in cis SAMD9L truncating mutations. Examination of 1 individual indicated that somatic reversions were postnatally selected. Somatic mutations were tracked to CD34 1 hematopoietic progenitor cell populations, being further enriched in B and NK cells. Stimulation of these cell types with interferon (IFN)-alpha or IFN-gamma induced SAMD9L expression. Clinically, revertant mosaicism was associated with milder disease, yet neurological manifestations persisted in 3 individuals. Two carriers also harbored a rare, in trans germ line SAMD9L missense loss-of-function variant, potentially counteracting the SAMD9L mutation. Our results demonstrate that gain-of-function mutations in the tumor suppressor SAMD9L cause cytopenia, immunodeficiency, variable neurological presentation, and predisposition to MDS with 27/del(7q), whereas hematopoietic revertant mosaicism commonly ameliorated clinical manifestations. The findings suggest a role for SAMD9L in regulating IFN-driven, demand-adapted hematopoiesis.
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| 2. |
- Davidsson, Kent, 1967, et al.
(författare)
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Potassium, chlorine, and sulfur in ash, particles, deposits, and corrosion during wood combustion in a circulating fluidized-bed boiler
- 2007
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 1520-5029 .- 0887-0624. ; 21:1, s. 71-81
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the addition of chlorine and/or sulfur to the fuel on fly ash composition, deposit formation, and superheater corrosion has been studied during biomass combustion in a circulating fluidized-bed boiler. The chlorine (HCl (aq)) and sulfur (SO2 (g)) were added in proportions of relevance for the potassium chemistry. The composition of the bottom and the fly ashes was analyzed. Gas and particle measurements were performed downstream of the cyclone before the convection pass and the flue gas composition was recorded in the stack with a series of standard instruments and an FTIR analyzer. At the position downstream of the cyclone, a deposit probe was situated, simulating a superheater tube. Deposits on the probe and initial corrosion were examined. It is concluded that addition of sulfur and chlorine increases the formation of submicron particles leading to deposition of potassium sulfate and chloride. The results compare well with earlier work based on laboratory-scale experiments concerning effects of chlorine and sulfur on potassium chemistry.
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| 3. |
- Johansson, Linda C, 1983, et al.
(författare)
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Structure of a photosynthetic reaction centre determined by serial femtosecond crystallography.
- 2013
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography is an X-ray free-electron-laser-based method with considerable potential to have an impact on challenging problems in structural biology. Here we present X-ray diffraction data recorded from microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8Å resolution and determine its serial femtosecond crystallography structure to 3.5Å resolution. Although every microcrystal is exposed to a dose of 33MGy, no signs of X-ray-induced radiation damage are visible in this integral membrane protein structure.
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| 4. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 5. |
- Andersson, Magnus, et al.
(författare)
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A proposed time-resolved X-ray scattering approach to track local and global conformational changes in membrane transport proteins
- 2008
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 16:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved X-ray scattering has emerged as a powerful technique for studying the rapid structural dynamics of small molecules in solution. Membrane-protein-catalyzed transport processes frequently couple large-scale conformational changes of the transporter with local structural changes perturbing the uptake and release of the transported substrate. Using light-driven halide ion transport catalyzed by halorhodopsin as a model system, we combine molecular dynamics simulations with X-ray scattering calculations to demonstrate how small-molecule time-resolved X-ray scattering can be extended to the study of membrane transport processes. In particular, by introducing strongly scattering atoms to label specific positions within the protein and substrate, the technique of time-resolved wide-angle X-ray scattering can reveal both local and global conformational changes. This approach simultaneously enables the direct visualization of global rearrangements and substrate movement, crucial concepts that underpin the alternating access paradigm for membrane transport proteins.
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| 6. |
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| 7. |
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| 8. |
- Andersson, Magnus, et al.
(författare)
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Structural Dynamics of Light-Driven Proton Pumps
- 2009
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 17:9, s. 1265-1275
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Tidskriftsartikel (refereegranskat)abstract
- Bacteriorhodopsin and proteorhodopsin are simple heptahelical proton pumps containing a retinal chromophore covalently bound to helix G via a protonated Schiff base. Following the absorption of a photon, all-trans retinal is isomerized to a 13-cis conformation, initiating a sequence of conformational changes driving vectorial proton transport. In this study we apply time-resolved wide-angle X-ray scattering to visualize in real time the helical motions associated with proton pumping by bacteriorhodopsin and proteorhodopsin. Our results establish that three conformational states are required to describe their photocycles. Significant motions of the cytoplasmic half of helix F and the extracellular half of helix C are observed prior to the primary proton transfer event, which increase in amplitude following proton transfer. These results both simplify the structural description to emerge from intermediate trapping studies of bacteriorhodopsin and reveal shared dynamical principles for proton pumping.
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| 9. |
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| 10. |
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| 11. |
- Andersson, S., et al.
(författare)
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Sulfur recirculation for increased electricity production in Waste-to-Energy plants
- 2014
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Ingår i: Waste Management. - : Elsevier BV. - 0956-053X .- 1879-2456. ; 34:1, s. 67-78
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Tidskriftsartikel (refereegranskat)abstract
- Sulfur recirculation is a new technology for reducing boiler corrosion and dioxin formation. It was demonstrated in full-scale tests at a Waste to Energy plant in Goteborg (Sweden) during nearly two months of operation. Sulfur was recirculated as sulfuric acid from the flue gas cleaning back to the boiler, thus creating a sulfur loop. The new technology was evaluated by extensive measurement campaigns during operation under normal conditions (reference case) and operation with sulfur recirculation. The chlorine content of both fly ash and boiler ash decreased and the sulfur content increased during the sulfur recirculation tests. The deposit growth and the particle concentration decreased with sulfur recirculation and the dioxin concentration (I-TEQ) of the flue gas was reduced by approximately 25%. Sulfuric acid dew point measurements showed that the sulfuric acid dosage did not lead to elevated SO3 concentrations, which may otherwise induce low temperature corrosion. In the sulfur recirculation corrosion probe exposures, the corrosion rate decreased for all tested materials (16Mo3, Sanicro 28 and Inconel 625) and material temperatures (450 degrees C and 525 degrees C) compared to the reference exposure. The corrosion rates were reduced by 60-90%. Sulfur recirculation prevented the formation of transition metal chlorides at the metal/oxide interface, formation of chromate and reduced the presence of zinc in the corrosion products. Furthermore, measured corrosion rates at 525 degrees C with sulfur recirculation in operation were similar or lower compared to those measured at 450 degrees C material temperature in reference conditions, which corresponds to normal operation at normal steam temperatures. This implies that sulfur recirculation allows for higher steam data and electricity production without increasing corrosion.
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| 12. |
- Aquila, Andrew, et al.
(författare)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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| 13. |
- Arnlund, David, et al.
(författare)
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Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:9, s. 923-926
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Tidskriftsartikel (refereegranskat)abstract
- We describe a method to measure ultrafast protein structural changes using time-resolved wide-angle X-ray scattering at an X-ray free-electron laser. We demonstrated this approach using multiphoton excitation of the Blastochloris viridis photosynthetic reaction center, observing an ultrafast global conformational change that arises within picoseconds and precedes the propagation of heat through the protein. This provides direct structural evidence for a 'protein quake': the hypothesis that proteins rapidly dissipate energy through quake-like structural motions.
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| 14. |
- Barty, A., et al.
(författare)
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Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
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Ingår i: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
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| 15. |
- Bergkvist, Markus, et al.
(författare)
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A Hybrid Micro-Simulator for Determining the Effects of Governmental Control Policies on Transport Chains
- 2005
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Ingår i: Multi-Agent and Multi-Agent Based Simulation. - New York City : Springer.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- A simulation-based tool is described which will be used to investigate how the actors in a transport chain are expected to act when different types of governmental control policies are applied, such as, fuel taxes, road tolls, vehicle taxes and requirements on vehicles. The simulator is composed of two layers, one layer simulating the physical activities taking place in the transport chain, e.g., production, storage, and transports of goods, and another layer simulating the different actors’ decision making processes. The decision layer is implemented by a multi-agent system where each agent corresponds to a particular actor and models the way it acts in different situations. The simulator will be used for analyzing the costs and environmental effects, and will in this way provide guidance in decision making regarding control policies. In addition, it will be possible for companies to use the simulator in order to determine cost-effective strategies given different (future) scenarios.
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| 16. |
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| 17. |
- Birch Tyrberg, Rasmus, et al.
(författare)
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Students’ and teachers’ attitudes towards PBL-curriculum components in a medical programme : a follow-up study
- 2021
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Ingår i: MedEdPublish. - : Association for Medical Education in Europe. - 2312-7996. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to explore students' and teachers' attitudes towards horizontal and vertical integration and other components of the curriculum, and to compare these results with data from a study at our medical school published in 2002.Methods: A questionnaire with 17 questions regarding different components of our curriculum was sent to students and staff at our medical school. They were asked to rate the importance of different components on a Likert scale from 1-6. We compared the answers between the two groups, and also compared them with the results from 2002.Results: Horizontal and vertical integration were rated as very important components (Teachers (n=283) median 5 and 5, Students (n=596) 6 and 5 respectively). Students valued lectures and clinical rotations more highly than teachers. Teachers considered laboratory training, training in searching scientific literature, scientific projects, basic education in ethics, reading and discussion of fictional literature, interprofessional components and examinations as significantly more important than the students did.Conclusions: Attitudes have remained positive towards horizontal and vertical integration despite major changes in the curriculum. The majority of the components of our curriculum were well appreciated, indicating that our curriculum is robust, but some components warrant inspection and possible revision.
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| 18. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 19. |
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| 20. |
- Borg, O Anders, et al.
(författare)
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Photochemistry of bromofluorobenzenes.
- 2006
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Ingår i: J Phys Chem A Mol Spectrosc Kinet Environ Gen Theory. - 1089-5639. ; 110, s. 7045-
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Tidskriftsartikel (refereegranskat)
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| 21. |
- Borg, O. Anders, et al.
(författare)
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Predissociation of Chlorobenzene, beyond the pseudo-diatomic model
- 2008
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 456:4-6, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of chlorobenzene via the lowest singlet excited state has been investigated by means of pump-probe femtosecond spectroscopy and spin-orbit corrected ab initio quantum chemistry. We have found that the so far accepted model with a (1)pi pi* -> (3)pi/n sigma* reaction mechanism has to be amended. We suggest that the mechanism goes via a transition from (1)pi pi* to a pi sigma* state that is to 90% a singlet. Further, three nuclear degrees of freedom required to describe the dissociation have been defined.
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| 22. |
- Borgström, Magnus, 1973-
(författare)
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Controlling Charge and Energy Transfer Processes in Artificial Photosynthesis : From Picosecond to Millisecond Dynamics
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes an interdisciplinary project, where the aim is to mimic the initial reactions in photosynthesis. In photosynthesis, the absorption of light is followed by the formation of charge-separated states. The energy stored in these charge-separated states is further used for the oxidation of water and reduction of carbon dioxide. In this thesis the photo-induced processes in a range of supramolecular complexes have been investigated with time resolved spectroscopic techniques. The complexes studied consist of three types of units; photosensitizers (P) capable of absorbing light, electron acceptors (A) that are easily reduced and electron donors (D) that are easily oxidised. Our results are important for the future design of artificial photosystems, where the goal is to produce hydrogen from light and water. Two molecular triads with a D-P-A architecture are presented. In the first one, a photo-induced charge-separated state was formed in an unusually high yield (φ>90%). In the second triad, photo-irradiation led to the formation of an extremely long-lived charge-separated state (τ = 500 ms at 140K). This is also the first synthetically made triad containing a dinuclear manganese unit as electron donor.Further, two sets of P-A dyads are presented. In both, the expected photo-induced reduction of the electron acceptor is diminished due to competing energy transfer to the triplet state of the acceptor.Finally, a P-P-A complex containing two separate photosensitizers is described. The idea is to produce high-energy charge-separated states by using the energy from two photons.
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| 23. |
- Brackmann, Christian, et al.
(författare)
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Optical and mass spectrometric study of the pyrolysis gas of wood particles
- 2003
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Ingår i: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 57:2, s. 216-222
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Tidskriftsartikel (refereegranskat)abstract
- A detailed experimental investigation has been made of the pyrolysis-the first step in biomass combustion-of single birchwood particles. In addition to mass spectrometric and gravimetric analysis, the pyrolysis volatiles were characterized by different optical techniques. Absorption measurements showed a nearly featureless absorption in the ultraviolet spectral region with a continuously stronger absorption for shorter wavelengths. Using different excitation wavelengths, laser-induced fluorescence measurements revealed generally broad spectra in the spectral region from 300-500 nm, which are characteristic spectral signatures for larger hydrocarbons. The optical data were monitored at different times in the pyrolysis process of the particles and compared with the results from the mass spectrometric and gravimetric analysis. The sensitivity of the optical techniques for differentiation between specific molecules was rather low, although formaldehyde could be observed both in absorption and fluorescence spectra. Laser-induced fluorescence measurements were also made for two-dimensional visualization of the pyrolysis volatiles; emitted from heated birchwood particles, indicating much higher flows along the fiber direction than across.
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| 24. |
- Carlsson, Bengt, et al.
(författare)
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Security Aspects on Inter-Organizational Cooperation Using Wrapper Agents
- 2005
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Konferensbidrag (refereegranskat)abstract
- The significance of electronic information exchange in interorganizational cooperation is well-known. We will here focus on the particular requirements of SMEs. We describe a general “wrapper agent” solution based on open source freeware that makes it possible (in principle) for any business system to exchange information with any other business system. It has been successfully applied in a pilot study involving two companies in a transport chain using different business systems. We also suggest further improvements by addressing security and privacy issues as well as an extended, possibly dynamic, set of involved companies and higher levels of cooperation.
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| 25. |
- Carlsson, Bengt, et al.
(författare)
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Security aspects on inter-organizational cooperation using wrapper agents
- 2009
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Konferensbidrag (refereegranskat)abstract
- The significance of electronic information exchange in inter-organizational cooperation is well-known. We will here focus on the particular requirements of SMEs. We describe a general wrapper agent solution based on open source freeware that makes it possible (in principle) for any business system to exchange information with any other business system. It has been successfully applied in a pilot study involving two companies in a transport chain using different business systems. We also suggest further improvements by addressing security issues as well as an extended, possibly dynamic, set of involved companies and higher levels of cooperation.
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