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Search Results: 1 - 10 of 470 matches for " Olof Lundberg "
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Calibration Systems of the ATLAS Tile Calorimeter
Olof Lundberg
Physics , 2012,
Abstract: TileCal is the hadronic calorimeter covering the most central region of the ATLAS experiment at the LHC. This sampling calorimeter uses iron plates as absorber and plastic scintillating tiles as the active material. A multi-faceted calibration system allows to monitor and equalize the calorimeter response at each stage of the signal production, from scintillation light to digitization. This calibration system is based on signal generation from different sources: a Cs radioactive source, laser light, charge injection and minimum bias events produced in proton-proton collisions. A brief description of the different TileCal calibration systems is given and the latest results on their performance in terms of calibration factors, linearity and stability are presented.
Analysis of transcript and protein overlap in a human osteosarcoma cell line
Daniel Klevebring, Linn Fagerberg, Emma Lundberg, Olof Emanuelsson, Mathias Uhlén, Joakim Lundeberg
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-684
Abstract: A large-scale analysis based on 2749 genes was performed, corresponding to approximately 13% of the protein coding genes in the human genome. We found the presence of both RNA and proteins to a large fraction of the analyzed genes with 60% of the analyzed human genes detected by all three methods. Only 34 genes (1.2%) were not detected on the transcriptional or protein level with any method. Our data suggest that the majority of the human genes are expressed at detectable transcript or protein levels in this cell line. Since the reliability of antibodies depends on possible cross-reactivity, we compared the RNA and protein data using antibodies with different reliability scores based on various criteria, including Western blot analysis. Gene products detected in all three platforms generally have good antibody validation scores, while those detected only by antibodies, but not by RNA sequencing, generally consist of more low-scoring antibodies.This suggests that some antibodies are staining the cells in an unspecific manner, and that assessment of transcript presence by RNA-seq can provide guidance for validation of the corresponding antibodies.Several studies have attempted to compare protein and transcript expression levels to investigate the central dogma of the cell, i.e. the relation between DNA, RNA and protein content in a cell [1-8]. Microarrays have been the prevalent platform to measure the abundance of transcripts in a sample, although other technologies such as SAGE have also been employed. The corresponding protein abundance estimates have frequently been obtained through mass spectrometry or protein arrays. The resulting correlation coefficients in these comparative analyses have varied significantly, from 0.3 to 0.9, comparing 10 s of genes up to 1000 s of genes. Sub-groups representing functionally different Gene Ontology groups could, however, display both higher and lower correlations depending on their role in the cellular machinery [7].To improve
Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
Mikael Fredrik Forsgren, Olof Dahlqvist Leinhard, Nils Dahlstr?m, Gunnar Cedersund, Peter Lundberg
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095700
Abstract: Objectives Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.
Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study
Johanna Gustafsson, Julia F Simard, Iva Gunnarsson, Kerstin Elvin, Ingrid E Lundberg, Lars-Olof Hansson, Anders Larsson, Elisabet Svenungsson
Arthritis Research & Therapy , 2012, DOI: 10.1186/ar3759
Abstract: 208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.
Poor mental health and sexual risk behaviours in Uganda: A cross-sectional population-based study
Patric Lundberg, Godfrey Rukundo, Schola Ashaba, Anna Thorson, Peter Allebeck, Per-Olof ?stergren, Elizabeth Cantor-Graae
BMC Public Health , 2011, DOI: 10.1186/1471-2458-11-125
Abstract: Household sampling was performed in two Ugandan districts, with 646 men and women aged 18-30 years recruited. Hopkins Symptoms Checklist-25 was used to assess the presence of depression and psychological distress. Alcohol use was assessed using a question about self-reported heavy-episodic drinking. Information on sexual risk behaviour was obtained concerning number of lifetime sexual partners, ongoing concurrent sexual relationships and condom use.Depression was associated with a greater number of lifetime partners and with having concurrent partners among women. Psychological distress was associated with a greater number of lifetime partners in both men and women and was marginally associated (p = 0.05) with having concurrent partners among women. Psychological distress was associated with inconsistent condom use among men. Alcohol use was associated with a greater number of lifetime partners and with having concurrent partners in both men and women, with particularly strong associations for both outcome measures found among women.Poor mental health is associated with sexual risk behaviours in a low-income sub-Saharan African setting. HIV preventive interventions should consider including mental health and alcohol use reduction components into their intervention packages, in settings where depression, psychological distress and alcohol use are common.Is poor mental health associated with sexual risk behaviours in sub-Saharan Africa? This question has not been conclusively answered despite its relevance for HIV prevention[1,2].Poor mental health is a major cause of disability in low-income countries, with depression constituting the heaviest disease burden[3]. The HIV epidemic may contribute to increased depression rates in countries having high HIV prevalence: HIV may lead to depression both in persons who live with HIV[4,5] and in those who are indirectly affected[6-8]. An association between depression and sexual risk behaviours is thus particularly relevant in
Increased Concentrations of Glutamate and Glutamine in Normal-Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans
Anders Tisell, Olof Dahlqvist Leinhard, Jan Bertus Marcel Warntjes, Anne Aalto, ?rjan Smedby, Anne-Marie Landtblom, Peter Lundberg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061817
Abstract: In Multiple Sclerosis (MS) the relationship between disease process in normal-appearing white matter (NAWM) and the development of white matter lesions is not well understood. In this study we used single voxel proton ‘Quantitative Magnetic Resonance Spectroscopy’ (qMRS) to characterize the NAWM and thalamus both in atypical ‘Clinically Definite MS’ (CDMS) patients, MRIneg (N = 15) with very few lesions (two or fewer lesions), and in typical CDMS patients, MRIpos (N = 20) with lesions, in comparison with healthy control subjects (N = 20). In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF) and severity of the disease measured using ‘Multiple Sclerosis Severity Score’ (MSSS). Elevated concentrations of glutamate and glutamine (Glx) were observed in both MS groups (MRIneg 8.12 mM, p<0.001 and MRIpos 7.96 mM p<0.001) compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr) with MSSS were 0.16±0.06 mM/MSSS (p = 0.02) for Glx and 0.06±0.03 mM/MSSS (p = 0.04) for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns) with BPF were ?6.22±1.63 mM/BPF (p<0.001) for tCr and ?7.71±2.43 mM/BPF (p = 0.003) for mIns. Furthermore, the MRIpos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA) and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001) and MRIneg (tNA: p = 0.03 , mIns: p = 0.002). The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.
Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome
Patrick Vigren, Anders Tisell, Maria Engstr?m, Thomas Karlsson, Olof Leinhard Dahlqvist, Peter Lundberg, Anne-Marie Landtblom
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056279
Abstract: Background Kleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus. Methods fMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods. Results There was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation. Conclusion This study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.
Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis Assessed with Quantitative MR
Janne West, Anne Aalto, Anders Tisell, Olof Dahlqvist Leinhard, Anne-Marie Landtblom, ?rjan Smedby, Peter Lundberg
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095161
Abstract: Introduction: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both ‘normal appearing white matter’ (NAWM) and ‘diffusely abnormal white matter’ (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes. In this study, qMRI and qMRS were used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to ‘normal white matter’ (NWM) in healthy controls. Methods: QMRI and qMRS measurements were performed on a 1.5 T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Twenty of the patients fulfilled the ‘Barkhof-Tintoré criteria’ for MS, (‘MRIpos’), whereas 15 showed radiologically atypical findings with few WM lesions (‘MRIneg’). QMRI properties were determined in ROIs of NAWM, DAWM and lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS. Results: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. R2 of DAWM was associated with BPF. Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. The correlation between qMRI and clinical status may shed new light on the clinicoradiological paradox.
Association between Change in Normal Appearing White Matter Metabolites and Intrathecal Inflammation in Natalizumab-Treated Multiple Sclerosis
Johan Mellerg?rd, Anders Tisell, Olof Dahlqvist Leinhard, Ida Blystad, Anne-Marie Landtblom, Kaj Blennow, Bob Olsson, Charlotte Dahle, Jan Ernerudh, Peter Lundberg, Magnus Vrethem
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044739
Abstract: Background Multiple sclerosis (MS) is associated not only with focal inflammatory lesions but also diffuse pathology in the central nervous system (CNS). Since there is no firm association between the amount of focal inflammatory lesions and disease severity, diffuse pathology in normal appearing white matter (NAWM) may be crucial for disease progression. Immunomodulating treatments for MS reduce the number of focal lesions, but possible effects on diffuse white matter pathology are less studied. Furthermore, it is not known whether intrathecal levels of inflammatory or neurodegenerative markers are associated with development of pathology in NAWM. Methods Quantitative proton magnetic resonance spectroscopy (1H-MRS) was used to investigate NAWM in 27 patients with relapsing MS before and after one year of treatment with natalizumab as well as NAWM in 20 healthy controls at baseline. Changes in 1H-MRS metabolite concentrations during treatment were also correlated with a panel of intrathecal markers of inflammation and neurodegeneration in 24 of these 27 patients. Results The group levels of 1H-MRS metabolite concentrations were unchanged pre-to posttreatment, but a pattern of high magnitude correlation coefficients (r = 0.43–0.67, p<0.0005–0.03) were found between changes in individual metabolite concentrations (total creatine and total choline) and levels of pro-inflammatory markers (IL-1β and CXCL8). Conclusions Despite a clinical improvement and a global decrease in levels of inflammatory markers in cerebrospinal fluid during treatment, high levels of pro-inflammatory CXCL8 and IL-1β were associated with an increase in 1H-MRS metabolites indicative of continued gliosis development and membrane turnover in NAWM.
Vascular endothelial growth factor (VEGF) expression in muscle tissue and the effect of corticosteroid therapy in patients with poly- and dermatomyositis
IE Lundberg
Arthritis Research & Therapy , 2002, DOI: 10.1186/ar451
Abstract: To further test this hypothesis we investigated if vascular endothelial growth factor (VEGF), which is upregulated by hypoxia, is expressed in muscle tissue in patients with PM and DM. A second aim was to investigate whether VEGF expression is affected by corticosteroid therapy.Six patients with PM and 4 with DM were investigated. A first muscle biopsy was taken at diagnosis and a second after 3–6 months with corticosteroid therapy. VEGF expression was investigated by immunohistochemistry using a rabbit polyclonal IgG antibody. Both conventional microscopic evaluation and computerised image analysis were used for evaluation of VEGF expression.These are our preliminary data: First biopsy: with conventional microscopic evaluation VEGF expression was observed in the endothelial cells of the microvessels in 9/10 patients and in larger vessels such as arterioles and venules in all patients. VEGF was also expressed in muscle fibres in all, and in mononuclear inflammatory cells in 3/10 patients. In the second biopsy, VEGF expression was still present in endothelial cells of capillaries and larger vessels as well as in muscle fibres, but with a seemingly weaker expression in the endothelial cells of PM patients and an increased expression in the DM patients. With computerised image analysis the results were similar.VEGF is expressed in endothelial cells of capillaries and slightly larger vessels, in muscle fibres, and in occasional inflammatory cells in muscle tissue from patients with poly- and dermatomyositis. After corticosteroid therapy the expression decreased in some patients and increased in other patients. Whether or not the changed VEGF expression has any clinical significance and correlates with changes in muscle function still needs to be analysed.
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