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  • Dicksved, Johan, et al. (författare)
  • Molecular characterization of the stomach microbiota in patients with gastric cancer and in controls
  • 2009
  • Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 58:4, s. 509-516
  • Tidskriftsartikel (refereegranskat)abstract
    • Persistent infection of the gastric mucosa by Helicobacter pylori can initiate an inflammatory cascade that progresses into atrophic gastritis, a condition associated with reduced capacity for secretion of gastric acid and an increased risk of developing gastric cancer. The role of H. pylori as an initiator of inflammation is evident but the mechanism for development into gastric cancer has not yet been proven. A reduced capacity for gastric acid secretion allows survival and proliferation of other microbes that normally are killed by the acidic environment. It has been postulated that some of these species may be involved in the development of gastric cancer; however, their identities are poorly defined. In this study, the gastric microbiota from ten patients with gastric cancer was characterized and compared with that from five dyspeptic controls using the molecular profiling approach terminal restriction fragment length polymorphism (T-RFLP), in combination with 16S rRNA gene cloning and sequencing. T-RFLP analysis revealed a complex bacterial community in the cancer patients that was not significantly different from that in the controls. Sequencing of 140 clones revealed 102 phylotypes, with representatives from five bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria). The data revealed a relatively low abundance of H. pylori and showed that the gastric cancer microbiota was instead dominated by different species of the genera Streptococcus, Lactobacillus, Veillonella and Prevotella. The respective role of these species in development of gastric cancer remains to be determined.
  • Gunnarsson, Rebeqa, et al. (författare)
  • Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-A comparative study of four differently designed, high resolution microarray platforms.
  • 2008
  • Ingår i: Genes, Chromosomes and Cancer. - : John Wiley and Sons Inc.. - 1045-2257 .- 1098-2264. ; 93, s. 0536-0536
  • Tidskriftsartikel (refereegranskat)abstract
    • Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
  • Hansson, Jenny, et al. (författare)
  • Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies
  • 2012
  • Ingår i: European Journal of Epidemiology. - : Springer. - 1573-7284 .- 0393-2990. ; 27:10, s. 771-779
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of snus (also referred to as Scandinavian or Swedish moist smokeless tobacco), which is common in Sweden and increasing elsewhere, is receiving increasing attention since considered a tobacco smoke "potential reduction exposure product". Snus delivers a high dose of nicotine with possible hemodynamic effects, but its impact on cardiovascular morbidity and mortality is uncertain. The aim of this study was to investigate whether snus use is associated with risk of and survival after acute myocardial infarction (AMI). Data from eight prospective cohort studies set in Sweden was pooled and reanalysed. The relative risk of first time AMI and 28-day case-fatality was calculated for 130,361 men who never smoked. During 2,262,333 person-years of follow-up, 3,390 incident events of AMI were identified. Current snus use was not associated with risk of AMI (pooled multivariable hazard ratio 1.04, 95 % confidence interval 0.93 to 1.17). The short-term case fatality rate appeared increased in snus users (odds ratio 1.28, 95 % confidence interval 0.99 to 1.68). This study does not support any association between use of snus and development of AMI. Hence, toxic components other than nicotine appear implicated in the pathophysiology of smoking related ischemic heart disease. Case fatality after AMI is seemingly increased among snus users, but this relationship may be due to confounding by socioeconomic or life style factors.
  • Heid, Iris M, et al. (författare)
  • Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
  • 2010
  • Ingår i: Nature genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 42:11, s. 949-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10(-9) to P = 1.8 × 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10(-3) to P = 1.2 × 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
  • Hoffman, Johan, et al. (författare)
  • Computability and Adaptivity in CFD
  • 2018. - 2
  • Ingår i: Encyclopedia of Computational Mechanics. - : John Wiley & Sons. - 9781119003793 - 9781119176817
  • Bokkapitel (refereegranskat)
  • Hoffman, Johan, et al. (författare)
  • Computation of slat noise sources using adaptive FEM and lighthill's analogy
  • 2013
  • Ingår i: 19th AIAA/CEAS Aeroacoustics Conference.
  • Konferensbidrag (refereegranskat)abstract
    • This is a summary of preliminary results from simulations with the 30P30N high-lift device. We used the General Galerkin finite element method (G2), where no explicit subgrid model is used, and where the computational mesh is adaptively refined with respect to a posteriori error estimates for a quantity of interest. The mesh is fully unstructured and the solutions are time-resolved, which are key ingredients for solving challenging industrial applications in the field of aeroacoustics. We present preliminary results containing time-averaged quantities and snapshots of unsteady quantities, all reasonably agreeing with previous computational efforts. One important finding is that the use of adaptively generated meshes seems to be a more effcient way of computing aeroacoustic sources than by using "handmade" meshes.
  • Hoffman, Johan, et al. (författare)
  • FEniCS-HPC : Automated predictive high-performance finite element computing with applications in aerodynamics
  • 2016
  • Ingår i: Proceedings of the 11th International Conference on Parallel Processing and Applied Mathematics, PPAM 2015. - : Springer-Verlag New York. ; , s. 356-365
  • Konferensbidrag (refereegranskat)abstract
    • Developing multiphysics nite element methods (FEM) andscalable HPC implementations can be very challenging in terms of soft-ware complexity and performance, even more so with the addition ofgoal-oriented adaptive mesh renement. To manage the complexity we inthis work presentgeneraladaptive stabilized methods withautomatedimplementation in the FEniCS-HPCautomatedopen source softwareframework. This allows taking the weak form of a partial dierentialequation (PDE) as input in near-mathematical notation and automati-cally generating the low-level implementation source code and auxiliaryequations and quantities necessary for the adaptivity. We demonstratenew optimal strong scaling results for the whole adaptive frameworkapplied to turbulent ow on massively parallel architectures down to25000 vertices per core with ca. 5000 cores with the MPI-based PETScbackend and for assembly down to 500 vertices per core with ca. 20000cores with the PGAS-based JANPACK backend. As a demonstration ofthe high impact of the combination of the scalability together with theadaptive methodology allowing prediction of gross quantities in turbulent ow we present an application in aerodynamics of a full DLR-F11 aircraftin connection with the HiLift-PW2 benchmarking workshop with goodmatch to experiments.
  • Hoffman, Johan, et al. (författare)
  • FEniCS-HPC: Coupled Multiphysics in Computational Fluid Dynamics
  • 2017
  • Ingår i: High-Performance Scientific Computing. - : Springer. - 9783319538617 - 9783319538624 ; , s. 58-69
  • Konferensbidrag (refereegranskat)abstract
    • We present a framework for coupled multiphysics in computational fluid dynamics, targeting massively parallel systems. Our strategy is based on general problem formulations in the form of partial differential equations and the finite element method, which open for automation, and optimization of a set of fundamental algorithms. We describe these algorithms, including finite element matrix assembly, adaptive mesh refinement and mesh smoothing; and multiphysics coupling methodologies such as unified continuum fluid-structure interaction (FSI), and aeroacoustics by coupled acoustic analogies. The framework is implemented as FEniCS open source software components, optimized for massively parallel computing. Examples of applications are presented, including simulation of aeroacoustic noise generated by an airplane landing gear, simulation of the blood flow in the human heart, and simulation of the human voice organ.
  • Hoffman, Johan, et al. (författare)
  • Time-resolved adaptive FEM simulation of the DLR-F11 aircraft model at high Reynolds number
  • 2014
  • Ingår i: 52nd AIAA Aerospace Sciences Meeting - AIAA Science and Technology Forum and Exposition, SciTech 2014. - 9781624102561
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • We present a time-resolved, adaptive finite element method for aerodynamics, together with the results from the HiLiftPW-2 workshop, where this method is used to compute the flow past a DLR-F11 aircraft model at realistic Reynolds number. The mesh is automatically constructed by the method as part of the computation, and no explicit turbulence model is needed. The effect of unresolved turbulent boundary layers is modeled by a simple parametrization of the wall shear stress in terms of the skin friction. In the extreme case of very high Reynolds numbers we approximate the small skin friction by zero skin friction, corresponding to a free slip boundary condition, which results in a computational model without any model parameter that needs tuning. Thus, the simulation methodology by- passes the main challenges posed by high Reynolds number CFD: the design of an optimal computational mesh, turbulence (or subgrid) modeling, and the cost of boundary layer res- olution. The results from HiLiftPW-2 presented in this report show good agreement with experimental data for a range of different angles of attack, while using orders of magnitude fewer degrees of freedom than what is needed in state of the art methods such as RANS. 
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