| 1. |
- Carlsén, Stefan, et al.
(författare)
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Cartilage oligomeric matrix protein induction of chronic arthritis in mice
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:7, s. 2000-2011
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a new mouse model for arthritis using cartilage oligomeric matrix protein (COMP) and to study the role of major histocompatibility complex (MHC) and Ncf1 genes in COMP-induced arthritis (COMPIA). METHODS: Native (pentameric) and denatured (monomeric) COMP purified from a rat chondrosarcoma was injected into mice with Freund's adjuvant to induce arthritis. C3H.NB, C3H.Q, B10.P, B10.Q, (B10.Q x DBA/1)F1, (BALB/c x B10.Q)F1, Ncf1 mutated, H-2Aq, H-2Ap, and human DR4+-transgenic mice were used. Anti-COMP antibodies and COMP levels in the immune sera were analyzed, and passive transfer of arthritis with purified immune sera was tested. RESULTS: Immunization with rat COMP induced a severe, chronic, relapsing arthritis, with a female preponderance, in the mice. The disease developed in C3H.NB mice, but not in B10.P mice, although they share the same MHC haplotype. Both H-2q and H-2p MHC haplotypes allowed the initiation of COMPIA. Using H-2Aq-transgenic and H-2Ap-transgenic mice, we demonstrated a role of both the Aq and Ep class II molecules in this model. Interestingly, the introduction of a mutation in the Ncf1 gene, which is responsible for the reduced oxidative burst phenotype, into the COMPIA-resistant B10.Q mouse strain rendered them highly susceptible to arthritis. In addition, the transfer of anti-COMP serum was found to induce arthritis in naive mice. Mice transgenic for the rheumatoid arthritis (RA)-associated DR4 molecule were found to be highly susceptible to COMPIA. CONCLUSION: Using rat COMP, we have developed a new and unique mouse model of chronic arthritis that resembles RA. This model will be useful as an appropriate and alternative model for studying the pathogenesis of RA.
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| 2. |
- Chubarova, Elena, et al.
(författare)
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Platinum zone plates for hard X-ray applications
- 2011
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 88:10, s. 3123-3126
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Tidskriftsartikel (refereegranskat)abstract
- We describe the fabrication and evaluation of platinum zone plates for 5–12 kV X-ray imaging and focusing. These nano-scale circular periodic structures are fabricated by filling an e-beam generated mold with Pt in an electroplating process. The plating recipe is described. The resulting zone plates, having outer zone widths of 100 and 50 nm, show good uniformity and high aspect ratio. Their diffraction efficiencies are 50–70% of the theoretical, as measured at the European Synchrotron Radiation Facility. Platinum shows promise to become an attractive alternative to present hard X-ray zone plate materials due to its nano-structuring properties and the potential for zone-plate operation at higher temperatures.
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| 3. |
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| 4. |
- Derefeldt, G., et al.
(författare)
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Improvement of tactical situation awareness with colour-coded horizontal-situation displays in combat aircraft
- 1999
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Ingår i: Displays (Guildford). - 0141-9382 .- 1872-7387. ; 20:4, s. 171-184
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Tidskriftsartikel (refereegranskat)abstract
- In the multi-role combat aircraft Gripen, the monochrome head-down displays in the cockpit are to be upgraded in colour. In the present study, the effects of colour-coded displays on visual search and situation awareness (SA) were studied in a real-time simulation of an air-to-air mission with test pilots as subjects. Gripen's monochrome colour scheme was compared to two chromatic (dichrome, polychrome) colour schemes. A 3×2×2 factorial within subjects design was used; the three colour schemes each with two different background conditions (simple and complex) and two different symbol configurations. The pilot had two tasks during the simulation: (1) to track a manoeuvring aircraft within specified limits by using the head-up display (HUD), and (2) to detect the appearance of a priority target on the head-down horizontal-situation display (HSD). Deviations in flight path angle and reaction times for target detection were recorded. After the test runs, the pilot answered questions and ranked the colour schemes in different respects. The pilot also rated them for SA using a subjective rating technique on cognitive compatibility (CC-SART). The results show that colour is advantageous in comparison to the monochrome display: The ranks on situation awareness and preference ratings were higher for the chromatic schemes, and with the complex background, the reaction times were significantly lower for the polychrome colour code. In summary, the results indicate that colour can improve tactical SA in combat aircraft.
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| 5. |
- Dubbelboer, Ilse R, et al.
(författare)
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Gastrointestinal mucus in dog : Physiological characteristics, composition, and structural properties
- 2022
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 173, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog.Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology.GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure.In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.
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| 6. |
- Eklöf, Mats, et al.
(författare)
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Workplace intervention for improved risk perception and preventive activity among workers : using hand-held vibrating machines: a pilot study
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This article presents a pilot study of a 1-h workplace educational intervention implemented among ten construction workers who were highly exposed to hand–arm vibration. The intervention combined risk communication and normative expert advice intended to reinforce preventive behaviour related to vibration, noise, and biomechanical loads. Data for this study comprised intervention notes and interview data from interventionists, and pre- and post-intervention interview data from participating workers.The results suggested that the intervention was sensitive to disturbances and should be directed only to motivated workers possessing sufficient self-efficacy, and only in circumstances in which exposure may be controlled on the local workplace level and by locally implemented measures. Unless these conditions are present, the studied intervention may fail to influence preventive behaviour, and may instead cause cognitive dissonance and frustration among participants and interventionists.
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| 7. |
- Gelderman, Kyra, et al.
(författare)
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T cell surface redox levels determine T cell reactivity and arthritis susceptibility.
- 2006
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 103:34, s. 12831-12836
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Tidskriftsartikel (refereegranskat)abstract
- Rats and mice with a lower capacity to produce reactive oxygen species (ROS) because of allelic polymorphisms in the Ncf1 gene (which encodes neutrophil cytosolic factor 1) are more susceptible to develop severe arthritis. These data suggest that ROS are involved in regulating the immune response. We now show that the lower capacity to produce ROS is associated with an increased number of reduced thiol groups (-SH) on T cell membrane surfaces. Artificially increasing the number of reduced thiols on T cells from animals with arthritis-protective Ncf1 alleles by glutathione treatment lowered the threshold for T cell reactivity and enhanced proliferative responses in vitro and in vivo. Importantly, T cells from immunized congenic rats with an E3-derived Ncf1 allele (DA.Ncf1E3 rats) that cannot transfer arthritis to rats with an arthritis-associated Dark Agouti (DA)-derived mutated Ncf1 allele (DA.Ncf1DA rats) became arthritogenic after increasing cell surface thiol levels. This finding was confirmed by the reverse experiment, in which oxidized T cells from DA.Ncf1DA rats induced less severe arthritis compared with controls. Therefore, we conclude that ROS production as controlled by Ncf1 is important in regulating surface redox levels of T cells and thereby suppresses autoreactivity and arthritis development.
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| 8. |
- Helldin, Tove, et al.
(författare)
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The Applicability of Human-Centred Automation Guidelines in the Fighter Aircraft Domain
- 2011
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Ingår i: Proceedings of the 29th European Conference on Cognitive Ergonomics (ECCE´11). - New York, NY, USA : Association for Computing Machinery (ACM). - 9781450310291 ; , s. 67-74
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Konferensbidrag (refereegranskat)abstract
- Motivation – To guide the development of human-centred automation within the fighter aircraft domain.Research approach – Identified human-centred automation guidelines have been analysed in relation to existing fighter aircraft automated functions together with system developers at Saab Aeronautics.Findings/Design – The results show that the human-centred automation guidelines have been considered during the development process. From these results, implications for the design of guidelines and for the design of automated systems in the aircraft domain are drawn.Research limitations/Implications – Deeper analysis of how automated functions can support pilots in future fighter aircraft is needed since the proposed guidelines are too general for the military fighter aircraft domain. Thus, future work involves an evaluation of the guidelines together with fighter aircraft system developers and/or military strategists. Such analysis must be carried out with specific automated functions in mind.Originality/Value – By comparing with existing automated functions, the research makes contributions to HCA guidelines to be used in the fighter aircraft domain. Suggestions of human-centred automation improvements within the fighter aircraft domain are presented. The analysis has also identified differences between the proposed guidelines and parts of the studied implementation examples.Take away message – The HCA guidelines must be adapted according to the specific tasks that the automated functions are intended to assist the operators with. To adapt the automation according to the level of experience of the operators as well as to expand the cooperative automation functions between aircraft in a team have been identified as future directions for automation improvements within the fighter aircraft domain.
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| 9. |
- Hertz, Hans M., et al.
(författare)
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Table-top X-ray microscopy : Sources, optics and applications
- 2003
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Ingår i: Journal de Physique IV. - : EDP Sciences. - 1155-4339 .- 1764-7177. ; 104, s. 115-119
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Tidskriftsartikel (refereegranskat)abstract
- We have developed the first operative compact sub-visible-resolution x-ray microscope for the water-window region (lambda = 2.3 - 4.4 nm). The microscope is based on a 100 Hz liquid-jet-target laser-plasma x-ray source, normal-incidence multilayer condenser optics, diffractive zone plate optics and CCD detection. In the present article we emphasize the system's aspects and summarize the recent progress on the components, all aiming at the reduction of the exposure time of a few seconds, i.e., similar to bending-magnet based microscopes. This primarily includes improved laser-plasma source, improved condenser optics using Cr/Sc multilayers, and improved image handling capability using wavelet algorithms. Such compact short-exposure time microscopes would significantly increase the applicability of the technology.
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| 10. |
- Holmberg, H, et al.
(författare)
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Developmental adaptation of rat nociceptive withdrawal reflexes after neonatal tendon transfer
- 1997
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Ingår i: JNeurosci. - 1529-2401. ; 17:6, s. 2071-2078
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Tidskriftsartikel (refereegranskat)abstract
- Nociceptive withdrawal reflexes (NWRs) were studied in adult rats in which the movement patterns produced by single muscles had been altered by neonatal tendon transfer. NWRs evoked by cutaneous noxious mechanical and thermal (CO2-laser) stimulation were recorded using electromyography in a decerebrate spinal preparation. The sensitivity distribution within the receptive fields of the NWRs of the extensor digitorum longus and the peronei muscles exhibited changes corresponding to the altered movement patterns. No detectable change of NWRs was found in normal muscles whose receptive fields overlapped that of the modified muscle. Furthermore, NWRs of muscles that regained an essentially normal function after neonatal tendon transfer did not differ from normal. It is proposed that a developmental experience-dependent mechanism, which takes into account the hindlimb movement pattern caused by contraction of single muscles, underlies the functionally adapted organization of adult NWRs.
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| 11. |
- Holmberg, Hans, et al.
(författare)
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Developmental adaptation of withdrawal reflexes to early alteration of peripheral innervation in the rat
- 1996
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 495:2, s. 399-409
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Tidskriftsartikel (refereegranskat)abstract
- 1. In adult decerebrate spinal rats whose plantar nerves (PLN) had been transected at either postnatal day 1. (P1) or P21 the nociceptive withdrawal reflexes (NWR) of musculi extensor digitorum longus (EDL), peroneus longus (PER) and semitendinosus (ST) were characterized with respect to receptive field (RF) organization, magnitude and time course, using electromyography. Thermal (short CO2 laser pulses) and mechanical (calibrated pinch) stimulation were used. The innervation patterns in normal and lesioned adult rats mrere assessed by acute nerve lesions. 2. The spatial organization of the mean mechano- and thermonociceptive RFs of all the muscles studied was similar to normal in both P1- and P21-lesioned rats, although in some P21-lesioned rats atypical EDL RFs were encountered. 3. In P1-lesioned rats thermo-NWR of PER and EDL had normal magnitudes, while mechano-NWR were reduced. In P21-lesioned rats both thermo- and mechano-NWR of these muscles had reduced magnitudes. Except for thermo-NWR of ST in P1-lesioned rats, which were increased, NWR of ST had normal magnitudes in both P1- and P21-lesioned rats. The time course of thermonociceptive NWR of the muscles studied were near normal in both P1- and P21-lesioned rats. 4. Acute nerve lesions in adult P1-lesioned rats revealed an essentially abolished contribution to NWR from the PLN. Instead, the contribution to NWR from other hindpaw nerves, such as the superficial and deep peroneal nerves, was dramatically increased. By contrast, in P21 lesioned rats, the regenerated PLN contributed significantly to the NWR. 5. It is concluded that despite profound alterations of plantar hindpaw innervation induced by early PLN transection the cutaneous nociceptive input to NWR attained an essentially normal spatial organization. An experience-dependent mechanism is suggested to be instrumental in adapting the reflex connectivity to the peripheral innervation.
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| 12. |
- Holmberg, Hans, et al.
(författare)
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Postnatal development of the nociceptive withdrawal reflexes in the rat : A behavioural and electromyographic study
- 1996
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Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 493:1, s. 239-252
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Tidskriftsartikel (refereegranskat)abstract
- 1. The postnatal development of nociceptive withdrawal reflexes was studied. In awake intact rats, forelimb, hindlimb and tail reflexes were recorded on videotape. In decerebrate spinal rats, electromyography (EMG) was used to record nociceptive withdrawal reflexes in musculi extensor digitorum longus (EDL), peronei, gastrocnemius-soleus (G-S) and biceps posterior-semitendinosus (BP-ST). Thermal (short-lasting CO2 laser pulses) and mechanical stimulation were used. 2. In adults, nociceptive withdrawal reflexes were typically well directed and reflex pathways to single hindlimb muscles had functionally adapted receptive fields. By contrast, at postnatal day (P) 1-7, the nociceptive withdrawal reflexes were often inappropriate, sometimes producing movements towards the stimulation, and EMG recordings revealed unadapted variable receptive fields. With increasing age, the nociceptive withdrawal reflexes progressively became well directed, thus producing localized withdrawal. Both withdrawal movements and spatial organization of the receptive fields were adult-like at P20-25. 3. Up to P25, reflex thresholds were more or less constant in both intact awake rats and spinal decerebrate rats, except in G-S in which no nociceptive withdrawal reflexes were evoked from P20 on. After P25, mechanical, but not thermal, thresholds increased dramatically. 4. EMG recordings revealed that during the first three postnatal weeks, the latency of the CO2 laser-evoked nociceptive withdrawal reflexes decreased significantly in peronei and BP-ST, but not in EDL, and thereafter increased significantly in peronei, BP-ST and EDL. The magnitude of the nociceptive withdrawal reflexes in these muscles increased markedly between P7 and P20 and showed little change thereafter. 5. Possible mechanisms underlying the postnatal tuning of the nociceptive withdrawal reflexes are discussed.
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| 13. |
- Holmberg, Jens, et al.
(författare)
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Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat.
- 2006
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Ingår i: Journal of Immunology. - 1550-6606. ; 176:2, s. 1172-1179
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Tidskriftsartikel (refereegranskat)abstract
- Pristane-induced arthritis (PIA) in rats, a model for rheumatoid arthritis (RA), is a T cell-dependent disease. However, pristane itself is a lipid and unable to form a stable complex with a MHC class II molecule. Therefore, the specificity and function of the T cells in PIA are as unclear as in rheumatoid arthritis. In this study, we show that activated CD4+ alphabetaT cells, which target peripheral joints, transfer PIA. The pristane-primed T cells are of oligo or polyclonal origin as determined by their arthritogenicity after stimulation with several mitogenic anti-TCRVbeta and anti-TCRValpha mAbs. Arthritogenic cells secreted IFN-gamma and TNF-alpha (but not IL-4) when stimulated with Con A in vitro, and pretreatments of recipient rats with either anti-IFN-gamma or a recombinant TNF-alpha receptor before transfer ameliorated arthritis development. Most importantly, we show that these T cells are MHC class II restricted, because treatment with Abs against either DQ or DR molecules ameliorates arthritis development. The MHC class II restriction was confirmed by transferring donor T cells to irradiated recipients that were syngenic, semiallogenic, or allogenic to MHC class II molecules, in which only syngenic and semiallogenic recipients developed arthritis. These data suggest that the in vivo administration of a non-antigenic adjuvant, like pristane, activates CD4+ alphabetaT cells that are MHC class II restricted and arthritogenic.
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| 14. |
- Holmberg, Jens
(författare)
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Reduced ROS production triggers arthritis / The role of T cells in arthritis pathogenesis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis is to defend a novel mechanism that triggers arthritis susceptibility in both rats and mice through reduced production of reactive oxygen species (ROS), but also to introduce a novel model for chronic relapsing arthritis. Five papers are included, all of which employ animal models for rheumatoid arthritis and one that also uses animal models for multiple sclerosis. Paper I aimed at identifying strong dominant loci operating early in PIA by linkage analysis of a large F2 backcross. We identified eight dominant QTLs regulating arthritis traits, of which Pia4 was the strongest in suppressing arthritis. Paper II aimed at cloning the gene responsible for the strong arthritis-suppressive effect of Pia4. Ncf1 was positionally identified as the only gene within a minimal Pia4-fragment with polymorphisms inside the coding region that differed between parental strains. Paper III aimed at showing that the arthritis-regulatory effect of Ncf1 is not species-specific. We showed that Ncf1-mutant mice were more susceptible to arthritis as well as to MOG protein-induced EAE than heterozygous littermate controls. Paper IV aimed at characterizing the immune response in PIA. Through several cell transfer experiments, we could conclude that T cell antigens must be involved in PIA, since arthritis transferred by T cells was restricted by MHC class II DQ and DR molecules. Paper V aimed at characterizing the chronic relapsing arthritis induced by adoptive transfer of PIA. High levels of COMP, AGP and IgG2b in blood at the chronic phase suggested cartilage destruction, systemic inflammation and Th1-mediated antibody production, respectively. Also, Methotrexate, anti-IFN-? or anti-TNF-? treatment with Etanercept ameliorated arthritis severity at the chronic stage.
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| 15. |
- Holmberg, Stig C, et al.
(författare)
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Anticipatory knowledge syntegrity : A way of linking individual and organisational knowledge management
- 2003
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Ingår i: Systemist. - 0961-8309. ; 25, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge Management (KM) is in most cases taken synonymously as Organisational Knowledge Management, i.e. procedures and measures on the organisational level. However, KM is also a matter for each individual knowledge worker in such organisations. Hence, Individual Knowledge Management will likewise be of paramount importance for modern knowledge organisations. Further, Individual and Organisational Knowledge Management have to be integrated into a mutually supporting whole. This integration is here called Anticipatory Knowledge Management and will be achieved by an adjusted form of Team Syntegrity in combination with anticipatory knowledge intensification and continuously co-created web spaces in intelligent networks.
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| 16. |
- Holmdahl, Rikard, et al.
(författare)
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Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis
- 2001
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Ingår i: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 184
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Forskningsöversikt (refereegranskat)abstract
- Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
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| 17. |
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| 18. |
- Hultqvist, Malin, et al.
(författare)
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A new arthritis therapy with oxidative burst inducers
- 2006
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Ingår i: PLoS Medicine. - 1549-1676. ; 3:9, s. 1625-1636
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite recent successes with biological agents as therapy for autoimmune inflammatory diseases such as rheumatoid arthritis ( RA), many patients fail to respond adequately to these treatments, making a continued search for new therapies extremely important. Recently, the prevailing hypothesis that reactive oxygen species (ROS) promote inflammation was challenged when polymorphisms in Ncf1, that decrease oxidative burst, were shown to increase disease severity in mouse and rat arthritis models. Based on these findings we developed a new therapy for arthritis using oxidative burst-inducing substances. Methods and Findings Treatment of rats with phytol ( 3,7,11,15-tetramethyl-2-hexadecene-1-ol) increased oxidative burst in vivo and thereby corrected the effect of the genetic polymorphism in arthritis-prone Ncf1 DA rats. Importantly, phytol treatment also decreased the autoimmune response and ameliorated both the acute and chronic phases of arthritis. When compared to standard therapies for RA, anti-tumour necrosis factor-alpha and methotrexate, phytol showed equally good or better therapeutic properties. Finally, phytol mediated its effect within hours of administration and involved modulation of T cell activation, as injection prevented adoptive transfer of disease with arthritogenic T cells. Conclusions Treatment of arthritis with ROS-promoting substances such as phytol targets a newly discovered pathway leading to autoimmune inflammatory disease and introduces a novel class of therapeutics for treatment of RA and possibly other chronic inflammatory diseases.
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| 19. |
- Hultqvist, Malin, et al.
(författare)
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Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene.
- 2004
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 101:34, s. 12646-12651
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Tidskriftsartikel (refereegranskat)abstract
- The Ncf1 gene was recently identified as a strong regulator of severe arthritis in rat. This finding was surprising, because the disease-promoting allele mediated a lower level of reactive oxygen species in NADPH oxidase-expressing cells. We have now investigated a splice mutation of the Ncf1 gene in B10.Q mice, causing a truncated and nonfunctional Ncf1 protein. We found that the mutated Ncf1 led to a more severe and chronic relapsing collagen-induced arthritis. Enhanced IgG and delayed-type hypersensitivity responses against type II collagen were seen, indicating increased activity of autoreactive T cells. Interestingly, female Ncf1-mutated mice spontaneously developed severe arthritis during the postpartum period. The arthritis was accompanied by an increased antibody response to type II collagen, with the same fine specificity as in collagen-induced arthritis. The enhancing effect of the mutated Ncf1 could also be shown to be more general in that it enhanced myelin oligodendrocyte glycoprotein protein-induced experimental autoimmune encephalomyelitis, a model for multiple sclerosis. These results show that Ncf1, a gene important for oxidative burst, regulates the susceptibility and severity of both arthritis and encephalomyelitis and modulates, directly or indirectly, the level of T cell-dependent autoimmune responses.
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| 20. |
- Karlsson, Mikael, et al.
(författare)
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Experimental determination of the aero-acoustic properties of an in-duct flexible plate
- 2008
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Ingår i: 14th AIAA/CEAS Aeroacoustics Conference (29th AIAA Aeroacoustics Conference). - Reston, Virigina : American Institute of Aeronautics and Astronautics (AIAA).
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Konferensbidrag (refereegranskat)abstract
- The potential reduction of the aeroacoustic noise generated by an in duct plate, byallowing it to be flexible, is studied experimentally. The test object is a triangular plateinserted at an angle in a circular flow duct. Results are given for the active and passiveacoustic properties. In addition the flow field and the vibrations of the plate arecharacterized. It is found that an appropriately yielding plate reduces the flow generatednoise while keeping the mean flow field unaffected.
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| 21. |
- Levinsson, Anders, et al.
(författare)
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Developmental tuning in a spinal nociceptive system: effects of neonatal spinalization
- 1999
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Ingår i: JNeurosci. - 1529-2401. ; 19:23, s. 10397-10403
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies indicate a modular organization of the nociceptive withdrawal reflex system. Each module has a characteristic receptive field, closely matching the withdrawal movement caused by its effector muscle. In the rat, the strength of the sensory input to each module is tuned during the first postnatal weeks, i.e., erroneous spinal connections are depressed, and adequate connections are strengthened. To clarify if this tuning is dependent on supraspinal structures, the effect of a complete neonatal spinal cord transection on the postnatal tuning of withdrawal reflexes was studied. The nociceptive receptive fields of single hindlimb muscles and compound withdrawal reflexes were examined in decerebrate unanesthetized and awake rats, respectively. Noxious thermal CO2 laser stimulation was used to evoke reflex responses. Neonatal spinal cord transection resulted in a disrupted reflex organization in the adult rat, resembling that previously found in neonatal rats. The receptive fields of single hindlimb muscles exhibited abnormal distribution of sensitivity not matching the withdrawal action of the effector muscles. Likewise, the composite nocifensive movements, as documented in the awake rat, often resulted in erroneous movements toward the stimulus. It is concluded that withdrawal reflexes do not become functionally adapted in rats spinalized at birth. These findings suggest a critical role for supraspinal systems in the postnatal tuning of spinal nociceptive systems.
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| 22. |
- Levinsson, Anders, et al.
(författare)
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Functional connections are established in the deafferented rat spinal cord by peripherally transplanted human embryonic sensory neurons
- 2000
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Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 12:10, s. 3589-3595
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Tidskriftsartikel (refereegranskat)abstract
- Functionally useful repair of the mature spinal cord following injury requires axon growth and the re-establishment of specific synaptic connections. We have shown previously that axons from peripherally grafted human embryonic dorsal root ganglion cells grow for long distances in adult host rat dorsal roots, traverse the interface between the peripheral and central nervous system, and enter the spinal cord to arborize in the dorsal horn. Here we show that these transplants mediate synaptic activity in the host spinal cord. Dorsal root ganglia from human embryonic donors were transplanted in place of native adult rat ganglia. Two to three months after transplantation the recipient rats were examined anatomically and physiologically. Human fibres labelled with a human-specific axon marker were distributed in superficial as well as deep laminae of the recipient rat spinal cord. About 36% of the grafted neurons were double labelled following injections of the fluorescent tracers MiniRuby into the sciatic and Fluoro-Gold into the lower lumbar spinal cord, indicating that some of the grafted neurons had grown processes into the spinal cord as well as towards the denervated peripheral targets. Electrophysiological recordings demonstrated that the transplanted human dorsal roots conducted impulses that evoked postsynaptic activity in dorsal horn neurons and polysynaptic reflexes in ipsilateral ventral roots. The time course of the synaptic activation indicated that the human fibres were non-myelinated or thinly myelinated. Our findings show that growing human sensory nerve fibres which enter the adult deafferentated rat spinal cord become anatomically and physiologically integrated into functional spinal circuits.
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| 23. |
- Levinsson, Anders, et al.
(författare)
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Spinal sensorimotor transformation: Relation between cutaneous somatotopy and a reflex network
- 2002
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 22:18, s. 8170-8182
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Tidskriftsartikel (refereegranskat)abstract
- The projection of primary afferents onto spinal interneurons constitutes the first step in sensorimotor transformations performed by spinal reflex systems. Despite extensive studies on spinal somatotopy, uncertainties remain concerning the extent and significance of representational overlap and relation to spinal reflex circuits. To address these issues, the cutaneous projection from the hindpaw and its relation to the topography of lamina V neurons encoding withdrawal reflex strength ("reflex encoders") was studied in rats. Thin and coarse primary afferent terminations in laminas II and III-IV, respectively, were mapped by wheat germ agglutinin-horseradish peroxidase and choleragenoid tracing. The functional weights of these projections were characterized by mapping nociceptive and tactile field potentials and compared with the topography of reflex encoders. Both anatomical and physiological data indicate that thin and coarse skin afferent input is spatially congruent in the horizontal plane. The representation of the hindpaw in the spinal cord was found to be intricate, with a high degree of convergence between the projections from different skin sites. "Somatotopic disruptions" such as the representation of central pads medial to that of the digits were common. The weight distribution of the cutaneous convergence patterns in laminas III-IV was similar to that of lamina V reflex encoders. This suggests that the cutaneous convergence and features such as somatotopic disruptions have specific relations to the sensorimotor transformations performed by reflex interneurons in the deep dorsal horn. Hence, the spinal somatotopic map may be better understood in light of the topography of such reflex systems.
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| 24. |
- Lind, Mikael, et al.
(författare)
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Service and Communication Infrastructure for Sea Traffic Management
- 2015
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Ingår i: 14th International Conference on Computer Applications and Information Technology in the Maritime Industries. ; , s. 290-305
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Konferensbidrag (refereegranskat)abstract
- The introduction of Sea Traffic Management services relies on infrastructures that enable trustworthy information sharing and service provisioning/consumption processes. For this purpose, a federated and regulated approach to information sharing and service distribution is proposed. Such an approach would position the governance of different services in the continuum of hierarchical (i.e.command and control) to market-driven approaches. In this paper the maritime infrastructure framework is presented and applied to Sea Traffic Management. The full potential and large-scale implementation would come when the same framework is applied in different areas of application that rely on information sharing, service interaction, and (digitized) actor collaboration.
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| 25. |
- Lu, Shemin, et al.
(författare)
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Both common and unique susceptibility genes in different rat strains with pristane-induced arthritis.
- 2002
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 10:8, s. 475-483
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Tidskriftsartikel (refereegranskat)abstract
- Pristane-induced arthritis (PIA) in rats is an animal model for rheumatoid arthritis (RA). We have previously identified seven quantitative trait loci (QTLs), which regulate arthritis development using a cross between the susceptible DA strain and the resistant E3 strain of rats (Pia2-8). In the present study the inbred rat strain LEW.1F was used as the susceptible strain in a cross with the E3 strain. The results confirmed the locus Pia4 on chromosome 12, which previously was shown to be associated with PIA, and also with experimental allergic encephalomyelitis, in crosses between the rat strains E3 and DA. On chromosome 1, linked to the albino locus, we identified a novel QTL, Pia9 in the LEW.F1 cross. This locus was associated with arthritis severity in the early phase of disease. A locus on chromosome 16, denoted Pia11, was also associated with arthritis severity in the early phase of the disease. A suggestive locus was detected on chromosome 14, which was associated with arthritis severity at the time when PIA progresses into a chronic phase. Using a congenic LEW.1F strain, which carries E3 alleles at the Pia9 locus, we confirmed that the E3 allele significantly suppresses arthritis severity during the early phase of the disease. The results revealed synergistic effects between different susceptibility loci using ANOVA analysis. These interactions were influenced by gender. Rats with Pia9 alleles from LEW.1F and Pia11 alleles from E3, were shown to suffer from much more severe arthritis in the early stage of the disease. On the other hand, the Pia9 and the suggestive locus on chromosome 14 affected only males during the chronic phase of the disease. These findings provide clues to how genetic factors by themselves, and in interaction with each other, regulate the development of a disease, which displays many similarities to RA.
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| 26. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 27. |
- Moesgaard, Jens Christian, et al.
(författare)
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På Uppdrag i Paris
- 2023
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Ingår i: Svensk Numismatisk Tidskrift. - 0283-071X. ; :8, s. 177-182
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Nielzén, Sören, et al.
(författare)
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Brain stem audiometry may supply markers for diagnostic and therapeutic control in psychiatry
- 2016
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940. ; 632, s. 163-168
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study is to try an alternative way of analyzing the ABR (Auditory Brainstem Response). The stimuli were complex sounds (c-ABR) as used in earlier studies. It was further aimed at corroborating earlier findings that this method can discriminate several neuropsychiatric states. Forty healthy control subjects, 26 subjects with the diagnosis schizophrenia (Sz) and 33 with ADHD (Attention deficit hyperactivity disorder) were recruited for the study. The ABRs were recorded. The analysis was based on calculation of areas of significantly group different time spans in the waves. Both latency and amplitude were thereby influential. The spans of differences were quantified for each subject in relation to the total area of the curve which made comparisons balanced. The results showed highly significant differences between the study groups. The results are important for future work on identifying markers for neuropsychiatric clinical use. To reach that goal calls for more extensive studies than this preliminary one.
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| 33. |
- Nilsson, Daniel, et al.
(författare)
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Ronchi test for characterization of nanofocusing optics at a hard x-ray free-electron laser
- 2012
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Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 37:24, s. 5046-5048
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of the classical Ronchi test to characterize aberrations in focusing optics at a hard x-ray free-electron laser. A grating is placed close to the focus and the interference between the different orders after the grating is observed in the far field. Any aberrations in the beam or the optics will distort the interference fringes. The methodis simple to implement and can provide single-shot information about the focusing quality. We used the Ronchi test to measure the aberrations in a nanofocusing Fresnel zone plate at the Linac Coherent Light Source at 8.194 keV.
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| 34. |
- Nilsson, Susanna, et al.
(författare)
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A Cognitive Systems Engineering Perspective on Fighter Cockpit Design Evaluation
- 2015
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Ingår i: HCI International 2015 - Posters’ Extended Abstracts. - Cham : Springer. - 9783319213828 - 9783319213835 ; , s. 628-633
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Konferensbidrag (refereegranskat)abstract
- In this paper a method for evaluating fighter aircraft cockpit design solutions is suggested, taking into account the specific needs and limitations that come from working in the context of developing modern fighter aircraft cockpit design. In this context flight simulators are an essential tool for evaluation. A general problem when using simulators for evaluations is the amount of data generated, and how to approach this data. There is a need to develop methods to manage the data and extract relevant data in order to make it usable in the design and development process. The approaches described also aim at connecting the simulator data to the overall joint goals of the pilot-fighter-aircraft system in accordance with the CSE approach to systems development.
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| 35. |
- Olofsson, Peter, et al.
(författare)
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A comparative genetic analysis between collagen-induced arthritis and pristane-induced arthritis.
- 2003
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 48:8, s. 2332-2342
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare the genetic regulation of collagen-induced arthritis (CIA) with that of pristane-induced arthritis (PIA) in rats. Methods A genome-wide linkage analysis of an (E3 × DA)DA backcross of rats with CIA (n = 364 male rats; the same strain combinations as previously used to determine the genetic control of PIA) was performed. The strongest loci in both CIA and PIA (i.e., Cia12/Pia4 and Cia13/Pia7) were isolated in congenic strains. Susceptibility in both congenic strains was tested in rats with CIA and in rats with PIA. Results We found a striking, although not complete, similarity of the arthritis-controlling loci in CIA and in PIA, as well as the previously defined loci associated with cartilage destruction, antibody production, and the acute-phase response. All major PIA quantitative trait loci (QTLs) identified in early severe arthritis were also strong regulators of CIA. The 2 strongest QTLs, Cia12/Pia4 on chromosome 12 and Cia13/Pia7 on chromosome 4, were also analyzed in congenic strains with DA or E3 as the background genome. Consistent with the results of linkage analysis, the congenic strain experiments showed that the chromosome 4 locus was more penetrant in CIA than in PIA, while the chromosome 12 locus almost completely dominated the control of PIA severity. Conclusion The underlying genetic control of CIA was found to have many, but not all, pathogenic mechanisms in common with PIA, despite the use of a cartilage-specific antigen (type II collagen) to induce CIA but not PIA.
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| 36. |
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| 37. |
- Olofsson, Peter, et al.
(författare)
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Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.
- 2003
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 33:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Schouenborg, Jens, et al.
(författare)
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Modular organization of spinal nociceptive reflexes : A New Hypothesis
- 1994
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Ingår i: News in Physiological Sciences. - : American Physiological Society. - 1522-161X. ; 9, s. 261-265
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Forskningsöversikt (refereegranskat)abstract
- Recent experimental studies suggest that the nociceptive withdrawal reflex system essentially has a "modular" organization, with each module concerned with the control of a single or a small group of muscles. This organizational principle appears to apply also to some spinoolivocerebellar pathways.
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| 42. |
- Sebelius, Fredrik, et al.
(författare)
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Classification of motor commands using a modified self-organising feature map.
- 2005
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Ingår i: Medical Engineering & Physics. - : Elsevier BV. - 1873-4030 .- 1350-4533. ; 27:5, s. 403-413
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a control system for an advanced prosthesis is proposed and has been investigated in two different biological systems: (1) the spinal withdrawal reflex system of a rat and (2) voluntary movements in two human males: one normal subject and one subject with a traumatic hand amputation. The small-animal system was used as a model system to test different processing methods for the prosthetic control system. The best methods were then validated in the human set-up. The recorded EMGs were classified using different ANN algorithms, and it was found that a modified self-organising feature map (SOFM) composed of a combination of a Kohonen network and the conscience mechanism algorithm (KNC) was superior in performance to the reference networks (e.g. multi-layer perceptrons) as regards training time, low memory consumption, and simplicity in finding optimal training parameters and architecture. The KNC network classified both experimental set-ups with high accuracy, including five movements for the animal set-up and seven for the human set-up.
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| 43. |
- Sköld, Mia, et al.
(författare)
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Thalamocortical abnormalities in auditory brainstem response patterns distinguish DSM-IV bipolar disorder type I from schizophrenia
- 2014
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 169, s. 105-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bipolar disorder type I (BP-I) belongs to a spectrum of affective disorders that are expressed in many different ways and therefore can be difficult to distinguish from other conditions, especially unipolar depression, schizoaffective disorder, schizophrenia (SZ), but also anxiety and personality disorders. Since early diagnosis and treatment have shown to improve the long-term prognosis, complementary specific biomarkers are of great value. The auditory brainstem response (ABR) has previously been applied successfully to identify specific abnormal ABR patterns in SZ and Asperger syndrome.METHODS: The current study investigated the early auditory processing of complex sound stimuli e.g. forward masking, in BP-I compared to SZ patients. The ABR curves of BP-I patients (n=23) and SZ patients (n=20) were analyzed in terms of peak amplitudes and correlation with an ABR norm curve based on a non-psychiatric control group (n=20).RESULTS: BP-I patients had significantly higher wave III (p=0.0062) and wave VII (p=0.0472) amplitudes compared with SZ patients. Furthermore, BP-I patients, and to a lesser extent SZ patients, showed low correlation with the norm ABR curve in the part of the curve comprising waves VI-VII.LIMITATIONS: Sample size was relatively small and study groups were not matched for age and gender.CONCLUSIONS: BP-I patients showed specific aberrances, specifically in the latter part of the ABR curve, implicating abnormalities in thalamocortical circuitry. The abnormal ABR wave patterns significantly separated BP-I patients from SZ patients suggesting that ABR might serve as a biomarker for BP-I.
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| 44. |
- Tuncel, Jonatan, et al.
(författare)
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Self-reactive T cells induce and perpetuate chronic relapsing arthritis
- 2020
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: CD4+ T cells play a central role during the early stages of rheumatoid arthritis (RA), but to which extent they are required for the perpetuation of the disease is still not fully understood. The aim of the current study was to obtain conclusive evidence that T cells drive chronic relapsing arthritis. Methods: We used the rat pristane-induced arthritis model, which accurately portrays the chronic relapsing-remitting disease course of RA, to examine the contribution of T cells to chronic arthritis. Results: Rats subjected to whole-body irradiation and injected with CD4+ T cells from lymph nodes of pristane-injected donors developed chronic arthritis that lasted for more than 4 months, whereas T cells from the spleen only induced acute disease. Thymectomy in combination with irradiation enhanced the severity of arthritis, suggesting that sustained lymphopenia promotes T cell-driven chronic inflammation in this model. The ability of T cells to induce chronic arthritis correlated with their expression of Th17-associated transcripts, and while depletion of T cells in rats with chronic PIA led to transient, albeit significant, reduction in disease, neutralization of IL-17 resulted in almost complete and sustained remission. Conclusion: These findings show that, once activated, self-reactive T cells can sustain inflammatory responses for extended periods of time and suggest that such responses are promoted in the presence of IL-17.
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| 45. |
- Wester, Lena, et al.
(författare)
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Differential gene expression in pristane-induced arthritis susceptible DA versus resistant E3 rats
- 2003
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1465-9905. ; 5:6, s. 361-372
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Tidskriftsartikel (refereegranskat)abstract
- Arthritis susceptibility genes were sought by analysis of differential gene expression between pristane-induced arthritis (PIA)-susceptible DA rats and PIA-resistant E3 rats. Inguinal lymph nodes of nave animals and animals 8 days after pristane injection were analyzed for differential gene expression. mRNA expression was investigated by microarray and real-time PCR, and protein expression was analyzed by flow cytometry or ELISA. Twelve genes were significantly differentially expressed when analyzed by at least two independent methods, and an additional five genes showed a strong a tendency toward differential expression. In nave DA rats IgE, the bone marrow stromal cell antigen 1 (Bst1) and the MHC class II -chain (MhcII) were expressed at a higher level, and the immunoglobulin kappa chain (Ig) was expressed at a lower level. In pristane-treated DA rats the MHC class II -chain, gelatinase B (Mmp9) and the protein tyrosine phosphatase CL100 (Ptpn16) were expressed at a higher level, whereas immunoglobulins, the CD28 molecule (Cd28), the mast cell specific protease 1 (Mcpt1), the carboxylesterase precursor (Ces2), K-cadherin (Cdh6), cyclin G1 (Ccng1), DNA polymerase IV (Primase) and the tumour associated glycoprotein E4 (Tage) were expressed at a lower level. Finally, the differentially expressed mRNA was confirmed with protein expression for some of the genes. In conclusion, the results show that animal models are well suited for reproducible microarray analysis of candidate genes for arthritis. All genes have functions that are potentially important for arthritis, and nine of the genes are located within genomic regions previously associated with autoimmune disease.
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