| 51. |
- Grund, Sofia, et al.
(författare)
-
The autocrine motility factor receptor is overexpressed on the surface of B cells in Binet C chronic lymphocytic leukemia.
- 2011
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 28:4, s. 1542-8
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a clinical spectrum reaching from discrete lymphocytosis to extensive enlargement of lymph nodes, spleen and liver, and bone marrow failure. The aim of this study was to identify genes that differentiate between patients with disease stage A vs. C according to Binet in order to better understand the disease. To achieve this, we performed DNA microarray analysis on B cells from CLL patients with stage A and C according to Binet and matched controls. Between CLL patients and controls, there were 1,528 differentially expressed genes and 360 genes were differentially expressed between Binet A and C patients. Due to the sheer number of regulated genes, we focused on the autocrine motility factor receptor (AMFR). AMFR has not previously been investigated in hematological disorders, but high expression of AMFR correlates with a more advanced stage and invasive potential in several human tumors. AMFR mRNA expression was higher in Binet A compared with Binet C patients (P=0.0053) and healthy controls (P=0.0051). Total AMFR protein was higher in Binet A patients compared to Binet C as analyzed by intracellular flow cytometry. However, AMFR exist both in the ER involved in protein degradation and on the cell surface involved in metastasis and cell motility. Cell surface AMFR was increased in Binet C compared with Binet A+B (P=0.016). In conclusion, the mRNA levels reflect the total amount of AMFR, whereas cell surface expression is associated with progression in CLL.
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| 52. |
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| 53. |
- Gyllenberg, A, et al.
(författare)
-
Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
-
Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
-
Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 54. |
- Hamann, C R, et al.
(författare)
-
Concentration variability of potent allergens of p-tert-Butylphenol-formaldehyde resin (PTBP-FR) in patch test preparations and commercially available PTBP-FR.
- 2012
-
Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 166:4, s. 761-770
-
Tidskriftsartikel (refereegranskat)abstract
- Background: p-tert-Butylphenol-formaldehyde resin (PTBP-FR) is a common component of glues used in the manufacturing of many plastic, electronic, rubber, wood, and leather products. Two main allergens of PTBP-FR have been described. Objectives: The objective of this study is to determine the concentrations of the two main allergens of PTBP-FR in diagnostic patch testing preparations and PTBP-FR available to glue and adhesive manufacturers. Methods: Nuclear magnetic resonance spectrometry (NMR) was used to confirm identity and determine the purity of reference materials. High-pressure liquid chromatography (HPLC) was used to analyse patch test preparations and commercially-available PTBP-FR. Results: In the PTBP-FR in analysed patch test preparations the highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 1.79% and the lowest 0.21%. The highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found in PTBP-FR of analysed patch test preparations was 0.50% and the lowest concentration found was 0.04%. In commercially-available PTBP-FR the highest concentration of -tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 3.7% and the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found was 1.1%. In three PTBP-FR samples neither allergen could be detected. Conclusions: Our data suggests that reporting resin concentration in petrolatum is not predictive of a consistent concentration of the two main allergens of PTBP-FR. The ten-fold difference in allergen concentration between different patch test preparations has significant ramifications for maintaining consistent dose of delivered allergen. The results of this study reinforce the need for patch test product standardization in the Contact Dermatitis community.
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| 55. |
- Hantke, Max F., et al.
(författare)
-
High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
-
Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
-
Tidskriftsartikel (refereegranskat)abstract
- We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
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| 56. |
- Hernandez-Perez, Adrian, et al.
(författare)
-
Analysis of twist stiffness of single and double-wall corrugated boards
- 2014
-
Ingår i: Composite structures. - : Elsevier BV. - 0263-8223 .- 1879-1085. ; 110, s. 7-15
-
Tidskriftsartikel (refereegranskat)abstract
- The twist stiffness of single and double-wall corrugated board is analyzed using first order shear deformation (FOSD) theory. Results are compared to finite element analysis (FEA) and dynamic test data for a large range of torsion loaded rectangular board specimens. The FOSD approach and FEA employ a homogenized core. In addition, a structural finite element model was developed where the web core is represented by shell elements. According to FOSD analysis, the twist stiffness is linearly dependent on the transverse shear moduli of the web core along both principal directions of the core. Good agreement between the torsional stiffness predictions by analytical and numerical approaches and test results is found for the range of single and double-wall boards examined. The FOSD solution is significantly less computationally demanding than FEA, and appears viable for prediction of the twist stiffness of corrugated board.
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| 57. |
- Heusser, Stephanie A., et al.
(författare)
-
Functional Validation of Virtual Screening for Novel Agents with General Anesthetic Action at Ligand-Gated Ion Channelss
- 2013
-
Ingår i: Molecular Pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0026-895X .- 1521-0111. ; 84:5, s. 670-678
-
Tidskriftsartikel (refereegranskat)abstract
- GABA(A) receptors play a crucial role in the actions of general anesthetics. The recently published crystal structure of the general anesthetic propofol bound to Gloeobacter violaceus ligand-gated ion channel (GLIC), a bacterial homolog of GABA(A) receptors, provided an opportunity to explore structure-based ligand discovery for pentameric ligand-gated ion channels (pLGICs). We used molecular docking of 153,000 commercially available compounds to identify molecules that interact with the propofol binding site in GLIC. In total, 29 compounds were selected for functional testing on recombinant GLIC, and 16 of these compounds modulated GLIC function. Active compounds were also tested on recombinant GABA(A) receptors, and point mutations around the presumed binding pocket were introduced into GLIC and GABA(A) receptors to test for binding specificity. The potency of active compounds was only weakly correlated with properties such as lipophilicity or molecular weight. One compound was found to mimic the actions of propofol on GLIC and GABA(A), and to be sensitive to mutations that reduce the action of propofol in both receptors. Mutant receptors also provided insight about the position of the binding sites and the relevance of the receptor's conformation for anesthetic actions. Overall, the findings support the feasibility of the use of virtual screening to discover allosteric modulators of pLGICs, and suggest that GLIC is a valid model system to identify novel GABA(A) receptor ligands.
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| 58. |
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| 59. |
- Hollerhage, M., et al.
(författare)
-
Piericidin A Aggravates Tau Pathology in P301S Transgenic Mice
- 2014
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The P301S mutation in exon 10 of the tau gene causes a hereditary tauopathy. While mitochondrial complex I inhibition has been linked to sporadic tauopathies. Piericidin A is a prototypical member of the group of the piericidins, a class of biologically active natural complex I inhibitors, isolated from streptomyces spp. with global distribution in marine and agricultural habitats. The aim of this study was to determine whether there is a pathogenic interaction of the environmental toxin piericidin A and the P301S mutation. Methods: Transgenic mice expressing human tau with the P301S-mutation (P301S(+/+)) and wild-type mice at 12 weeks of age were treated subcutaneously with vehicle (N=10 P301S(+/+), N = 7 wild-type) or piericidin A (N = 9 P301S(+/+), N = 9 wild-type mice) at a dose of 0.5 mg/kg/d for a period of 28 days via osmotic minipumps. Tau pathology was measured by stereological counts of cells immunoreative with antibodies against phosphorylated tau (AD2, AT8, AT180, and AT100) and corresponding Western blot analysis. Results: Piericidin A significantly increased the number of phospho-tau immunoreactive cells in the cerebral cortex in P301S(+/+) mice, but only to a variable and mild extent in wild-type mice. Furthermore, piericidin A led to increased levels of pathologically phosphorylated tau only in P301S(+/+) mice. While we observed no apparent cell loss in the frontal cortex, the synaptic density was reduced by piericidin A treatment in P301S(+/+) mice. Discussion: This study shows that exposure to piericidin A aggravates the course of genetically determined tau pathology, providing experimental support for the concept of gene-environment interaction in the etiology of tauopathies.
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| 60. |
- Inayat, S, et al.
(författare)
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High levels of cathepsins B, L and S in human seminal plasma and their association with prostasomes
- 2012
-
Ingår i: Andrologia. - : Hindawi Limited. - 0303-4569 .- 1439-0272. ; 44:6, s. 423-427
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Tidskriftsartikel (refereegranskat)abstract
- Semen is a heterogenous and complex fluid with different functions, some of them well known, others still obscure. The aim of this study was to investigate the presence of cathepsins B, S and L in human seminal plasma and their possible associations with other semen variables. Cathepsin B, L and S concentrations were measured in seminal plasma from 99 men utilising commercial ELISA kits. Seminal plasma cathepsin B was approximately 70 times higher, while the cathepsin L values were approximately 500 times higher and the cathepsin S values approximately 40 times higher in seminal plasma than in a group of serum samples. The study shows that seminal plasma contains high levels of cathepsins B, L and S. All three cathepsins were also bound to the surface of prostasomes.
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| 61. |
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| 62. |
- Johansen, Kari, et al.
(författare)
-
Estimates of Healthcare and Non-Healthcare Costs due to Severe Rotavirus Infections leading to Hospitalization in Swedish Children (<5 years)
- 2011
-
Konferensbidrag (refereegranskat)abstract
- Introduction: Estimates of economic benefit of rotavirus vaccination depend on the accuracy of calculated country-specific costs related to rotavirus gastroenteritis (RVGE). Transmission of disease to family members adds to the economic burden through loss of caregiver productivity. The aim of this study was to assess costs related to severe RVGE.Material and methods: A prospective, observational study was conducted in a large hospital in the Stockholm region, serving a population of 66,222 children < 5 years. RVGE related health care resource use and time off work were collected from a sample of families with hospitalised children due to community- and nosocomially-derived RVGE (n=153). Health care related costs were calculated using 2008 DRG reimbursement for acute diarrhoea and productivity loss using self reported absence combined with 2008 Swedish average cost for a working hour (€28) from SCB/Statistics Sweden.Results: Median age of hospitalised children was 15 months. For caregivers, average workday loss due to children's, siblings or own disease was 4.2 days and 1.2 days, respectively. Estimated average total cost per child was €3227, €1949 (60%) for health -care related costs, €1186 (37%) productivity loss and €92 (3%) due to other indirect costs.Conclusions: Economic burden of RVGE is primarily driven by costs related to in-patient care, sensitive to unit cost used. However, loss of productivity is also significant in spite of generous parental allowance in Sweden, 12-18 months per child. A limitation of this study is that productivity loss from care for non-hospitalized children and its household members was not assessed.
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| 63. |
- Johnsson, Andreas, 1977, et al.
(författare)
-
THE ORIGIN OF STRIPE-LIKE PATTERNS ON MARTIAN GULLY SLOPES; USING SVALBARD ADVENT VALLEY AS A MARS ANALOGUE.
- 2010
-
Ingår i: 41st Lunar and Planetary Science Conference. ; :1665
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Stripes are a common slope features in polar regions on Earth were active layer processes (freezing/thawing and gelifluction) occur. Their origin is most likely polygenic and closely related to frost crack plygons and sorted circles with the addition of a gravitational component. Stripes are either sorted or unsorted. Features resembling stripes have been observed on slopes on Mars with or without association with polygons. Due to the current temperature and pressure regime on Mars soil moisture and active layer processes are not likely to occur. However, in recent HiRISE images stripelike patterns can be observed in proximity to gullies . Stripe width typically ranges from ~50 cm to 1.5 m, and their orientation is consistently down slope, although it can not be excluded that it sometimes slightly deviates from the steepest topographic gradient. In our study we have examined sorted and nonsorted stripes on slopes in Svalbard in order to test the working hypothesis of an cryoturbation origin for the martian stripe-like patterns. In doing so we compare their morphological characteristics, settings, and slope to those on Mars.
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| 64. |
- Kahsai, Lily, et al.
(författare)
-
Distribution of metabotropic receptors of serotonin, dopamine, GABA, glutamate, and short neuropeptide F in the central complex of Drosophila
- 2012
-
Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 208, s. 11-26
-
Tidskriftsartikel (refereegranskat)abstract
- The central complex is a prominent set of midline neuropils in the insect brain, known to be a higher locomotor control center that integrates visual inputs and modulates motor outputs. It is composed of four major neuropil structures, the ellipsoid body (EB), fan-shaped body (FB), noduli (NO), and protocerebral bridge (PB). In Drosophila different types of central complex neurons have been shown to express multiple neuropeptides and neurotransmitters; however, the distribution of corresponding receptors is not known. Here, we have mapped metabotropic, G-protein–coupled receptors (GPCRs) of several neurotransmitters to neurons of the central complex. By combining immunocytochemistry with GAL4 driven green fluorescent protein, we examined the distribution patterns of six different GPCRs: two serotonin receptor subtypes (5-HT1B and 5-HT7), a dopamine receptor (DopR), the metabotropic GABAB receptor (GABABR), the metabotropic glutamate receptor (DmGluRA) and a short neuropeptide F receptor (sNPFR1). Five of the six GPCRs were mapped to different neurons in the EB (sNPFR1 was not seen). Different layers of the FB express DopR, GABABR, DmGluRA, and sNPFR1, whereas only GABABR and DmGluRA were localized to the PB. Finally, strong expression of DopR and DmGluRA was detected in the NO. In most cases the distribution patterns of the GPCRs matched the expression of markers for their respective ligands. In some nonmatching regions it is likely that other types of dopamine and serotonin receptors or ionotropic GABA and glutamate receptors are expressed. Our data suggest that chemical signaling and signal modulation are diverse and highly complex in the different compartments and circuits of the Drosophila central complex. The information provided here, on receptor distribution, will be very useful for future analysis of functional circuits in the central complex, based on targeted interference with receptor expression.
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| 65. |
- Keefover-Ring, Ken, et al.
(författare)
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2 '-(Z)-Cinnamoylsalicortin : A novel salicinoid isolated from Populus tremula
- 2014
-
Ingår i: Phytochemistry Letters. - : Elsevier BV. - 1874-3900 .- 1876-7486. ; 7, s. 212-216
-
Tidskriftsartikel (refereegranskat)abstract
- Using a combination of NMR and mass spectroscopic techniques, we have isolated a new salicinoid from the foliage of European aspen (Populus tremula) and identified it as 2'-(Z)-cinnamoylsalicortin. The relatively high amounts in foliage and the similarity in structure to bioactive salicinoids isolated from other salicaceous trees indicates that this compound may have implications for the study of P. tremulaherbivore interactions.
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| 66. |
- Knævelsrud, Helene, et al.
(författare)
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Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation
- 2013
-
Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 202:2, s. 331-349
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Tidskriftsartikel (refereegranskat)abstract
- The membrane remodeling events required for autophagosome biogenesis are still poorly understood. Because PX domain proteins mediate membrane remodeling and trafficking, we conducted an imaging-based siRNA screen for autophagosome formation targeting human PX proteins. The PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation, and its Drosophila melanogaster homologue SH3PX1 was found to be required for efficient autophagosome formation in the larval fat body. We show that SNX18 is required for recruitment of Atg16L1-positive recycling endosomes to a perinuclear area and for delivery of Atg16L1- and LC3-positive membranes to autophagosome precursors. We identify a direct interaction of SNX18 with LC3 and show that the pro-autophagic activity of SNX18 depends on its membrane binding and tubulation capacity. We also show that the function of SNX18 in membrane tubulation and autophagy is negatively regulated by phosphorylation of S233. We conclude that SNX18 promotes autophagosome formation by virtue of its ability to remodel membranes and provide membrane to forming autophagosomes.
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| 67. |
- Knævelsrud, Helene, et al.
(författare)
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SNX18 tubulates recycling endosomes for autophagosome biogenesis
- 2013
-
Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 9:10, s. 1639-1641
-
Tidskriftsartikel (refereegranskat)abstract
- The role of membrane remodeling and phosphoinositide-binding proteins in autophagy remains elusive. PX domain proteins bind phosphoinositides and participate in membrane remodeling and trafficking events and we therefore hypothesized that one or several PX domain proteins are involved in autophagy. Indeed, the PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation using an image-based siRNA screen. We show that SNX18 interacts with ATG16L1 and LC3, and functions downstream of ATG14 and the class III PtdIns3K complex in autophagosome formation. SNX18 facilitates recruitment of ATG16L1 to perinuclear recycling endosomes, and its overexpression leads to tubulation of ATG16L1- and LC3-positive membranes. We propose that SNX18 promotes LC3 lipidation and tubulation of recycling endosomes to provide membrane for phagophore expansion.
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| 68. |
- Laadan, Boaz, et al.
(författare)
-
Furaldehyde substrate specificity and kinetics of Saccharomyces cerevisiae alcohol dehydrogenase 1 variants
- 2014
-
Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A previously discovered mutant of Saccharomyces cerevisiae alcohol dehydrogenase 1 (Adh1p) was shown to enable a unique NADH-dependent reduction of 5-hydroxymethylfurfural (HMF), a well-known inhibitor of yeast fermentation. In the present study, site-directed mutagenesis of both native and mutated ADH1 genes was performed in order to identify the key amino acids involved in this substrate shift, resulting in Adh1p-variants with different substrate specificities. Results: In vitro activities of the Adh1p-variants using two furaldehydes, HMF and furfural, revealed that HMF reduction ability could be acquired after a single amino acid substitution (Y295C). The highest activity, however, was reached with the double mutation S110P Y295C. Kinetic characterization with both aldehydes and the in vivo primary substrate acetaldehyde also enabled to correlate the alterations in substrate affinity with the different amino acid substitutions. Conclusions: We demonstrated the key role of Y295C mutation in HMF reduction by Adh1p. We generated and kinetically characterized a group of protein variants using two furaldehyde compounds of industrial relevance. Also, we showed that there is a threshold after which higher in vitro HMF reduction activities do not correlate any more with faster in vivo rates of HMF conversion, indicating other cell limitations in the conversion of HMF.
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| 69. |
- Lindvall, Karin, et al.
(författare)
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Daily dosing prophylaxis for haemophilia : A randomized crossover pilot study evaluating feasibility and efficacy
- 2012
-
Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 18:6, s. 855-859
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Tidskriftsartikel (refereegranskat)abstract
- Regular replacement therapy (prophylaxis) for haemophilia has been shown to prevent development of disabling arthropathy and to provide a better quality of life compared to treatment on demand; however, at a substantially higher cost. Calculations based on pharmacokinetic principles have shown that shortening dose intervals may reduce cost. The aim of this prospective, randomized, crossover pilot study was to address whether daily dosing is feasible, if it reduces concentrate consumption and is as effective in preventing bleeding as the standard prophylactic dosing regimen. In a 12 + 12 month crossover study, 13 patients were randomized to start either their own previously prescribed standard dose, or daily dosing adjusted to maintain at least the same trough levels as obtained with the standard dose. Ten patients completed the study. A 30% reduction in cost of factor concentrates was achieved with daily prophylaxis. However, the number of bleeding events increased in some patients in the daily dosing arm and patients reported decreased quality of life during daily prophylaxis. Daily treatment had a greater impact on daily life, and the patients found it more stressful.Prophylaxis with daily dosing may be feasible and efficacious in some patients. A substantial reduction of factor consumption and costs can be realized, but larger studies are needed before the introduction of daily prophylaxis into clinical routine can be recommended.
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| 70. |
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| 71. |
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| 72. |
- Lundmark, Richard, et al.
(författare)
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Driving membrane curvature in clathrin-dependent and clathrin-independent endocytosis.
- 2010
-
Ingår i: Seminars in Cell and Developmental Biology. - : Elsevier BV. - 1084-9521 .- 1096-3634. ; 21:4, s. 363-70
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Tidskriftsartikel (refereegranskat)abstract
- Cellular activity depends to a large extent on membrane bilayer dynamics. Many processes, such as organelle biogenesis and vesicular transport, rely on alterations in membrane structure and shape. It is now widely accepted that intracellular membrane curvature generation and remodelling is mediated and regulated by protein action, and the mechanisms behind the processes are currently being revealed. Here, we will briefly discuss the key principles of membrane deformation and focus on different endocytic events that use various kinds of proteins to shape the plasma membrane into transport carriers. The entry routes are adopted to make sure that a vast variety of molecules on the cell surface can be regulated by endocytosis. The principles for membrane sculpting of endocytic carriers can be viewed either from a perspective of rigid coat budding or of flexible opportunistic budding. We will discuss these principles and their implications, focusing on clathrin-dependent and -independent carrier formation and the proteins involved in the respective pathways.
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| 73. |
- Marquez, Marcel, et al.
(författare)
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Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk
- 2012
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:2, s. 524-530
-
Tidskriftsartikel (refereegranskat)abstract
- It has recently been suggested that the low-frequency c.136-14-136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14-136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14-136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease. © 2012 by the American Diabetes Association.
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| 74. |
- Marshall, N.S., et al.
(författare)
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Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study
- 2011
-
Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 38:6, s. 1349-1354
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Tidskriftsartikel (refereegranskat)abstract
- Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean±sd body mass index 41±5 kg·m−2). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40–2.18)). In a range of multivariate models of mortality risk, controlling for ≤16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01–1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.
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| 75. |
- Mielke, Michelle M, et al.
(författare)
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Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease.
- 2014
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 35:11, s. 2486-94
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Tidskriftsartikel (refereegranskat)abstract
- Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but invivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with AβX-38 (r= 0.312, p= 0.003), AβX-40 (r= 0.327, p= 0.002), and T-tau (r= 0.313, p= 0.003) but not with AβX-42 (r= 0.171, p= 0.106) or p-tau (r= 0.086, p= 0.418). All sphingomyelin species correlated (most p < 0.001) with all Aβ species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest invivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Aβ and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis.
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| 76. |
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| 77. |
- Mustafa, M., et al.
(författare)
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Diverse collective excitations in Er-159 up to high spin
- 2011
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:5
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Tidskriftsartikel (refereegranskat)abstract
- A spectroscopic investigation of the gamma decays from excited states in Er-159 has been performed to study the changing structural properties exhibited as ultrahigh spins (I > 60 (h) over bar) are approached. The nucleus of Er-159 was populated by the reaction Cd-116(Ca-48, 5n gamma) at a beam energy of 215 MeV, and the resulting gamma decays were studied using the Gammasphere spectrometer. New rotational bands and extensions to existing sequences were observed, which are discussed in terms of the cranked shell model, revealing a diverse range of quasiparticle configurations. At spins around 50 (h) over bar, there is evidence for a change from dominant prolate collective motion at the yrast line to oblate non-collective structures via the mechanism of band termination. A possible strongly deformed triaxial band occurs at these high spins, which indicates collectivity beyond 50 (h) over bar. The high-spin data are interpreted within the framework of cranked Nilsson-Strutinsky calculations.
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| 78. |
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| 79. |
- Palmer, C. N. A., et al.
(författare)
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Paradoxical Lower Serum Triglyceride Levels and Higher Type 2 Diabetes Mellitus Susceptibility in Obese Individuals with the PNPLA3 148M Variant
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. Methods and Findings: PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O. R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction = 0.002). This provides evidence for the obesity interaction with 148M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study. Conclusions: Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.
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| 80. |
- Perk, Joep, et al.
(författare)
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Allvarliga brister i rådgivning till koronarsjuka patienter efter ballongvidgning patienter undervärderar levnadsvanors betydelse, visar enkätstudie
- 2014
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 111:42, s. 1835-
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Tidskriftsartikel (refereegranskat)abstract
- In a questionnaire 1073 patients from 29 randomly selected Swedish hospitals who had undergone percutaneous coronary intervention (PCI) were asked what they considered to be the cause of their coronary disease, how they experienced the information given by the medical staff and in which way had they adopted a heart-healthy lifestyle. The main outcomes were; A majority attributed the cause of the disease to non-modifiable factors, i.e. age and heredity. Merely one in four patients had perceived the information in a correct way: they still carried the coronary disease and needed to adapt their lifestyle. Half of the patient population had increased their physical activity and likewise merely half had changed their food habits. Half of the tobacco users had quit after PCI. Thus the results of this study shows that there is ample space for improving the present care of post-PCI patients.
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| 81. |
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| 82. |
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| 83. |
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| 84. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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| 85. |
- Rath, Asawari D., et al.
(författare)
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Explosion dynamics of sucrose nanospheres monitored by time of flight spectrometry and coherent diffractive imaging at the split-and-delay beam line of the FLASH soft X-ray laser
- 2014
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Ingår i: Optics Express. - 1094-4087. ; 22:23, s. 28914-28925
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Tidskriftsartikel (refereegranskat)abstract
- We use a Mach-Zehnder type autocorrelator to split and delay XUV pulses from the FLASH soft X-ray laser for triggering and subsequently probing the explosion of aerosolised sugar balls. FLASH was running at 182 eV photon energy with pulses of 70 fs duration. The delay between the pump-probe pulses was varied between zero and 5 ps, and the pulses were focused to reach peak intensities above 1016 W/cm2 with an off-axis parabola. The direct pulse triggered the explosion of single aerosolised sucrose nano-particles, while the delayed pulse probed the exploding structure. The ejected ions were measured by ion time of flight spectrometry, and the particle sizes were measured by coherent diffractive imaging. The results show that sucrose particles of 560-1000 nm diameter retain their size for about 500 fs following the first exposure. Significant sample expansion happens between 500 fs and 1 ps. We present simulations to support these observations.
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| 86. |
- Reiss, Dennis, et al.
(författare)
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TERRESTRIAL GULLIES ON SVALBARD AS PLANETARY ANALOGS FOR MARS
- 2010
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Ingår i: 41st Lunar and Planetary Science Conference. ; :2492
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Martian gullies resemble terrestrial gul-lies, which are formed by a combination of processes includ-ing mass wasting, overland flow and debris flows. The gullies on Mars show several morphologic features such as braided channels, multiple terraces, point bars and cutbanks, which indicate that fluvial processes were involved in their formation. However, it remains unclear whether fluvial processes or debris flows are dominating the formation of gullies on Mars. Debris flows are viscous slurry flows with water and fines as the interstitial fluid. The flowing mix-tures of fines, clastic debris and water has a relatively low water content (≤ 30 % water by weight). Stream flows and hyperconcentrated flows have a high water content and relatively low sediment supply (≥ 30 % water by weight). The morphologies of debris flows fans show typical fea-tures such as levées, lobes, snouts and debris plugs, which are not observed from purely fluvial processes. In this work we compare the morphology of terrestrial gully analogs from Svalbard with Martian gullies in order to constrain which formation process might be dominant on Mars, i.e. fluvial and/or debris flow processes.
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| 87. |
- Rudolph, Dirk, et al.
(författare)
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Alpha-Photon Coincidence Spectroscopy Along Element 115 Decay Chains
- 2014
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Ingår i: Acta Physica Polonica. Series B: Elementary Particle Physics, Nuclear Physics, Statistical Physics, Theory of Relativity, Field Theory. - 0587-4254. ; 45, s. 263-272
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Tidskriftsartikel (refereegranskat)abstract
- Produced in the reaction 48Ca+243Am, thirty correlated α-decay chains were observed in an experiment conducted at the GSI Helmholzzentrum für Schwerionenforschung, Darmstadt, Germany. The decay chains are basically consistent with previous findings and are considered to originate from isotopes of element 115 with mass numbers 287, 288, and 289. A set-up aiming specifically for high-resolution charged particle and photon coincidence spectroscopy was placed behind the gas-filled separator TASCA. For the first time, γ rays as well as X-ray candidates were observed in prompt coincidence with the α-decay chains of element 115.
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| 88. |
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| 89. |
- Rudolph, Dirk, et al.
(författare)
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Spectroscopy of Element 115 Decay Chains
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:11
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Tidskriftsartikel (refereegranskat)abstract
- A high-resolution , X-ray and gamma-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated alpha-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z = 115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z > 112. Comprehensive Monte-Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.
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| 90. |
- Ruiz-Pavon, Lorena, et al.
(författare)
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Functionally important amino acids in the Arabidopsis thylakoid phosphate transporter: Homology modeling and site-directed mutagenesis
- 2010
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Ingår i: Biochemistry. - : American Chemical Society. - 0006-2960 .- 1520-4995. ; 49:30, s. 6430-6439
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Tidskriftsartikel (refereegranskat)abstract
- The anion transporter 1 (ANTR1) from Arabidopsis thaliana, homologous to the mammalian members of the solute carrier 17 (SLC17) family, is located in the chloroplast thylakoid membrane. When expressed heterologously in Escherichia coli, ANTR1 mediates a Na+-dependent active transport of inorganic phosphate (Pi). The aim of this study was to identify amino acid residues involved in Pi binding and translocation by ANTR1 and in the Na+ dependence of its activity. A three-dimensional structural model of ANTR1 was constructed using the crystal structure of glycerol 3-phosphate/phosphate antiporter from E. coli as a template. Based on this model and multiple sequence alignments, five highly conserved residues in plant ANTRs and mammalian SLC17 homologues have been selected for site-directed mutagenesis, namely, Arg-120, Ser-124, and Arg-201 inside the putative translocation pathway and Arg-228 and Asp-382 exposed at the cytoplasmic surface of the protein. The activities of the wild-type and mutant proteins have been analyzed using expression in E. coli and radioactive Pi transport assays and compared with bacterial cells carrying an empty plasmid. The results from Pi- and Na+-dependent kinetics indicate the following: (i) Arg-120 and Arg-201 may be important for binding and translocation of the substrate; (ii) Ser-124 may function as a transient binding site for Na+ ions in close proximity to the periplasmic side; (iii) Arg-228 and Asp-382 may participate in interactions associated with protein conformational changes required for full transport activity. Functional characterization of ANTR1 should provide useful insights into the function of other plant and mammalian SLC17 homologous transporters.
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| 91. |
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| 92. |
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| 93. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 94. |
- Svalkvist, Angelica, et al.
(författare)
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Investigation of the effect of varying scatter-to-primary ratios on nodule contrast in chest tomosynthesis
- 2011
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Ingår i: Medical Imaging 2011. - : SPIE - International Society for Optical Engineering. - 9780819485038 ; 7961
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The primary aim of the present work was to analyze the effects of varying scatter-to-primary ratios on the appearance of simulated nodules in chest tomosynthesis section images. Monte Carlo simulations of the chest tomosynthesis system GE Definium 8000 VolumeRAD (GE Healthcare, Chalfont St. Giles, UK) were used to investigate the variation of scatter-to-primary ratios between different angular projections. The simulations were based on a voxel phantom created from CT images of an anthropomorphic chest phantom. An artificial nodule was inserted at 80 different positions in the simulated phantom images, using five different approaches for the scatter-to-primary ratios in the insertion process. One approach included individual determination of the scatter-to primary-ratio for each projection image and nodule location, while the other four approaches were using mean value, median value and zero degree projection value of the scatter-to-primary ratios at each nodule position as well as using a constant scatter-to-primary ratio of 0.5 for all nodule positions. The results indicate that the scatter-to-primary ratios vary up to a factor of 10 between the different angular tomosynthesis projections (±15°). However, the error in the resulting nodule contrast introduced by not taking all variations into account is in general smaller than 10 %.
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| 95. |
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| 96. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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CDKN2B expression and subcutaneous adipose tissue expandability: Possible influence of the 9p21 atherosclerosis locus
- 2014
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 446:4, s. 1126-1131
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Tidskriftsartikel (refereegranskat)abstract
- Risk alleles within a gene desert at the 9p21 locus constitute the most prevalent genetic determinant of cardiovascular disease. Previous research has demonstrated that 9p21 risk variants influence gene expression in vascular tissues, yet the biological mechanisms by which this would mediate atherosclerosis merits further investigation. To investigate possible influences of this locus on other tissues, we explored expression patterns of 9p21-regulated genes in a panel of multiple human tissues and found that the tumor suppressor CDKN2B was highly expressed in subcutaneous adipose tissue (SAT). CDKN2B expression was regulated by obesity status, and this effect was stronger in carriers of 9p21 risk alleles. Covariation between expression of CDKN2B and genes implemented in adipogenesis was consistent with an inhibitory effect of CDKN2B on SAT proliferation. Moreover, studies of postprandial triacylglycerol clearance indicated that CDKN2B is involved in down-regulation of SAT fatty acid trafficking. CDKN2B expression in SAT correlated with indicators of ectopic fat accumulation, including markers of hepatic steatosis. Among genes regulated by 9p21 risk variants, CDKN2B appears to play a significant role in the regulation of SAT expandability, which is a strong determinant of lipotoxicity and therefore might contribute to the development of atherosclerosis. (C) 2014 The Authors. Published by Elsevier Inc.
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| 97. |
- Söderberg, Jeannette A. E., et al.
(författare)
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Insulin-producing cells in the Drosophila brain also express satiety-inducing cholecystokinin-like peptide, drosulfakinin
- 2012
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of meal size and assessing the nutritional value of food are two important aspects of feeding behavior. The mechanisms that regulate these two aspects have not been fully elucidated in Drosophila. Diminished signaling with insulin-like peptides Drosophila insulin-like peptides (DILPs) affects food intake in flies, but it is not clear what signal(s) mediates satiety. Here we investigate the role of DILPs and drosulfakinins (DSKs), cholecystokinin-like peptides, as satiety signals in Drosophila. We show that DSKs and DILPs are co-expressed in insulin-producing cells (IPCs) of the brain. Next we analyzed the effects of diminishing DSKs or DILPs employing the Gal4-UAS system by (1) diminishing DSK-levels without directly affecting DILP levels by targeted Dsk-RNAi, either in all DSK-producing cells (DPCs) or only in the IPCs or (2) expressing a hyperpolarizing potassium channel to inactivate either all the DPCs or only the IPCs, affecting release of both peptides. The transgenic flies were assayed for feeding and food choice, resistance to starvation, and for levels of Dilp and Dsk transcripts in brains of fed and starved animals. Diminishment of DSK in the IPCs alone is sufficient to cause defective regulation of food intake and food choice, indicating that DSK functions as a hormonal satiety signal in Drosophila. Quantification of Dsk and Dilp transcript levels reveals that knockdown of either peptide type affects the transcript levels of the other, suggesting a possible feedback regulation between the two signaling pathways. In summary, DSK and DILPs released from the IPCs regulate feeding, food choice and metabolic homeostasis in Drosophila in a coordinated fashion.
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| 98. |
- Thomson, R M., et al.
(författare)
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On the biological basis for competing macroscopic dose descriptors for kilovoltage dosimetry: cellular dosimetry for brachytherapy and diagnostic radiology
- 2013
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Ingår i: Physics in Medicine and Biology. - : Institute of Physics. - 0031-9155 .- 1361-6560. ; 58:4, s. 1123-1150
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work is to investigate how alternative macroscopic dose descriptors track absorbed dose to biologically relevant subcellular targets via Monte Carlo (MC) analysis of cellular models for a variety of cancerous and normal soft tissues for kilovoltage radiation. The relative mass distributions of water, light inorganic elements, and protein components of nuclear and cytoplasm compartments for various tissues are determined from a literature review. These data are used to develop representative cell models to demonstrate the range of mass elemental compositions of these subcellular structures encountered in the literature from which radiological quantities (energy absorption and attenuation coefficients; stopping powers) are computed. Using representative models of cell clusters, doses to subcellular targets are computed using MC simulation for photon sources of energies between 20 and 370 keV and are compared to bulk medium dose descriptors. It is found that cells contain significant and varying mass fractions of protein and inorganic elements, leading to variations in mass energy absorption coefficients for cytoplasm and nuclear media as large as 10% compared to water for sub-50 keV photons. Doses to subcellular structures vary by as much as 23% compared to doses to the corresponding average bulk medium or to small water cavities embedded in the bulk medium. Relationships between cellular target doses and doses to the bulk medium or to a small water cavity embedded in the bulk medium are sensitive to source energy and cell morphology, particularly for lower energy sources, e. g., low energy brachytherapy (andlt;50 keV). Results suggest that cells in cancerous and normal soft tissues are generally not radiologically equivalent to either water or the corresponding average bulk tissue. For kilovoltage photon sources, neither dose to bulk medium nor dose to water quantitatively tracks energy imparted to biologically relevant subcellular targets for the range of cellular morphologies and tissues considered.
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| 99. |
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| 100. |
- Ullman, Gustaf, et al.
(författare)
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A Monte Carlo-based model for simulation of digital chest tomosynthesis
- 2010
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Ingår i: Radiation Protection Dosimetry. - Oxford : Oxford University Press. - 0144-8420 .- 1742-3406. ; 139:1-3, s. 159-163
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to calculate synthetic digital chest tomosynthesis projections using a computer simulation model based on the Monte Carlo method. An anthropomorphic chest phantom was scanned in a computed tomography scanner, segmented and included in the computer model to allow for simulation of realistic high-resolution X-ray images. The input parameters to the model were adapted to correspond to the VolumeRAD chest tomosynthesis system from GE Healthcare. Sixty tomosynthesis projections were calculated with projection angles ranging from +15 to −15°. The images from primary photons were calculated using an analytical model of the anti-scatter grid and a pre-calculated detector response function. The contributions from scattered photons were calculated using an in-house Monte Carlo-based model employing a number of variance reduction techniques such as the collision density estimator. Tomographic section images were reconstructed by transferring the simulated projections into the VolumeRAD system. The reconstruction was performed for three types of images using: (i) noise-free primary projections, (ii) primary projections including contributions from scattered photons and (iii) projections as in (ii) with added correlated noise. The simulated section images were compared with corresponding section images from projections taken with the real, anthropomorphic phantom from which the digital voxel phantom was originally created. The present article describes a work in progress aiming towards developing a model intended for optimisation of chest tomosynthesis, allowing for simulation of both existing and future chest tomosynthesis systems.
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