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Sökning: WFRF:(Johansson Mikael) > (2005-2009)

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  • Covacu, Ruxandra, et al. (författare)
  • Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis
  • 2006
  • Ingår i: Stem Cells. - : AlphaMed Press. - 1549-4918 .- 1066-5099. ; 24:12, s. 2792-2800
  • Tidskriftsartikel (refereegranskat)abstract
    • Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and beta-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.
  • Ludvigsson, Johnny, et al. (författare)
  • GAD treatment and insulin secretion in recent-onset type 1 diabetes
  • 2008
  • Ingår i: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
  • Mu, Xiangkui, et al. (författare)
  • Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study.
  • 2005
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X .- 1651-226X. ; 44:6, s. 554-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH).Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively.This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.
  • Andersson, Anna, et al. (författare)
  • Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
  • 2007
  • Ingår i: Leukemia. - : Nature Publishing Group. - 1476-5551 .- 0887-6924. ; 21:6, s. 1198-1203
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
  • Bexell, U., et al. (författare)
  • Bonding of vegetable oils to mercapto silane treated metal surfaces : Surface engineering on the nano scale
  • 2006
  • Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 515:2, s. 838-841
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper the bonding of thin vegetable oil films on mercapto silane treated aluminium surfaces has been studied. The silane molecules are attached to the surface by metal-oxygen-silicon bonds. The coupling between the unsaturated bonds of the vegetable oil and the thiol functionalised surface was obtained through a photoinduced thiol-ene reaction. The surfaces were characterised by X-ray photoelectron spectroscopy (XPS). Vegetable oil contains both saturated and unsaturated carbon chains. For the reactions investigated in this study it is the unsaturated carbon chains that can react by a thiol-ene reaction and the results indicate that it is possible to attach a vegetable oil to a metal surface pre-treated with a thiol functionalised silane.
  • Glimelius, B., et al. (författare)
  • Number of patients potentially eligible for proton therapy
  • 2005
  • Ingår i: Acta Oncol. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 44:8, s. 836-49
  • Tidskriftsartikel (refereegranskat)abstract
    • A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.
  • Johansson, Björn, et al. (författare)
  • Distributed Model Predictive Consensus
  • 2006
  • Ingår i: Proceedings of the 17th International Symposium on Mathematical Theory of Networks and Systems. ; , s. 2438-2444
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we consider the problem of designing a distributed control strategy such that a linear combination of the states of a number of vehicles coincide at a given time. The vehicles are described by linear difference equations and are subject to convex input constraints. It is demonstrated how primal decomposition techniques and incremental subgradient methods allow us to find a solution in which each vehicle performs individual planning of its trajectory and exchanges critical information with neighbors only. We explore various communication, computation, and control structures, and demonstrate the performance of the algorithms by numerical examples.
  • Johansson, Björn, et al. (författare)
  • On decentralized negotiation of optimal consensus
  • 2008
  • Ingår i: Automatica. - 0005-1098 .- 1873-2836. ; 44:4, s. 1175-1179
  • Tidskriftsartikel (refereegranskat)abstract
    • A consensus problem consists of finding a distributed control strategy that brings the state or output of a group of agents to a common value, a consensus point. In this paper, we propose a negotiation algorithm that computes an optimal consensus point for agents modeled as linear control systems subject to convex input constraints and linear state constraints. By primal decomposition and incremental subgradient methods, it is shown that the algorithm can be implemented such that each agent exchanges only a small amount of information per iteration with its neighbors.
  • Johansson, Björn, et al. (författare)
  • Subgradient methods and consensus algorithms for solving convex optimization problems
  • 2008
  • Ingår i: Decision and Control, 2008. CDC 2008. 47th IEEE Conference on. - : IEEE. - 9781424431236 ; , s. 4185-4190
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we propose a subgradient method for solving coupled optimization problems in a distributed way given restrictions on the communication topology. The iterative procedure maintains local variables at each node and relies on local subgradient updates in combination with a consensus process. The local subgradient steps are applied simultaneously as opposed to the standard sequential or cyclic procedure. We study convergence properties of the proposed scheme using results from consensus theory and approximate subgradient methods. The framework is illustrated on an optimal distributed finite-time rendezvous problem.
  • Olabarrieta, Idoia, et al. (författare)
  • Aging properties of films of plasticized vital wheat gluten cast from acidic and basic solutions
  • 2006
  • Ingår i: Biomacromolecules. - : American Chemical Society. - 1525-7797 .- 1526-4602. ; 7:5, s. 1657-1664
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to understand the mechanisms behind the undesired aging of films based on vital wheat gluten plasticized with glycerol, films cast from water/ethanol solutions were investigated. The effect of pH was studied by casting from solutions at pH 4 and pH 11. The films were aged for 120 days at 50% relative humidity and 23 C, and the tensile properties and oxygen and water vapor permeabilities were measured as a function of aging time. The changes in the protein structure were determined by infrared spectroscopy and size-exclusion and reverse-phase high-performance liquid chromatography, and the film structure was revealed by optical and scanning electron microscopy. The pH 11 film was mechanically more stable with time than the pH 4 film, the latter being initially very ductile but turning brittle toward the end of the aging period. The protein solubility and infrared spectroscopy measurements indicated that the protein structure of the pH 4 film was initially significantly less polymerized/ aggregated than that of the pH 11 film. The polymerization of the pH 4 film increased during storage but it did not reach the degree of aggregation of the pH 11 film. Reverse-phase chromatography indicated that the pH 11 films were to some extent deamidated and that this increased with aging. At the same time a large fraction of the aged pH 11 film was unaffected by reducing agents, suggesting that a time-induced isopeptide cross-linking had occurred. This isopeptide formation did not, however, change the overall degree of aggregation and consequently the mechanical properties of the film. During aging, the pH 4 films lost more mass than the pH 11 films mainly due to migration of glycerol but also due to some loss of volatile mass. Scanning electron and optical microscopy showed that the pH 11 film was more uniform in thickness and that the film structure was more homogeneous than that of the pH 4 film. The oxygen permeability was also lower for the pH 11 film. The fact that the pH 4 film experienced a larger and more rapid change in its mechanical properties with time than the pH 11 film, as a consequence of a greater loss of plasticizer, was presumably due to its initial lower degree of protein aggregation/ polymerization. Consequently, the cross-link density achieved at pH 4 was too low to effectively retain volatiles and glycerol within the matrix.
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