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  • Chuang, Shu-Chun, et al. (författare)
  • Circulating Biomarkers of Tryptophan and the Kynurenine Pathway and Lung Cancer Risk
  • 2014
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965. ; 23:3, s. 461-468
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Imbalances in tryptophan metabolism have been linked to cancer-related immune escape and implicated in several cancers, including lung cancer. Methods: We conducted a nested case-control study within the European Prospective Investigation into Cancer andNutrition (EPIC) that included 893 incident lung cancer cases and 1,748matched controls. Circulating levels of tryptophan and six of its metabolites were measured and evaluated in relation to lung cancer risk. Results: Tryptophan (P-trend = 2 Chi 10(-5)) and the kynurenine/ tryptophan ratio (KTR; P-trend 4 Chi 10(-5)) were associated with lung cancer risk overall after adjusting for established risk factors. The ORs comparing the fifth and first quintiles (OR5th (vs. 1st)) were 0.52 [ 95% confidence interval (CI), 0.37-0.74] for tryptophan and 1.74 (95% CI, 1.24-2.45) for KTR. After adjusting for plasma methionine (available fromprevious work, which was strongly correlated with tryptophan), the associations of tryptophan (adjusted P-trend 0.13) and KTR (P-trend = 0.009) were substantially attenuated. KTR was positively associated with squamous cell carcinoma, the OR5th vs. 1st being 2.83 (95% CI, 1.62-4.94, P-trend -3 Chi 10(-5)) that was only marginally affected by adjusting for methionine. Conclusions: This study indicates that biomarkers of tryptophan metabolism are associated with subsequent lung cancer risk. Although this result would seem consistent with the immune system having a role in lung cancer development, the overall associations were dependent on methionine, and further studies are warranted to further elucidate the importance of these metabolites in lung cancer etiology. Impact: This is the first prospective study investigating the tryptophan pathway in relation to lung cancer risk.
  • Dai, Juncheng, et al. (författare)
  • Genome-wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk
  • 2019
  • Ingår i: International Journal of Cancer. - John Wiley & Sons. - 0020-7136.
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large-scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large-scale meta-analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome-wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.
  • Dewi, Nikmah Utami, et al. (författare)
  • Anthropometry and the risk of lung cancer in EPIC
  • 2016
  • Ingår i: American Journal of Epidemiology. - Oxford University Press. - 0002-9262. ; 184:2, s. 129-139
  • Tidskriftsartikel (refereegranskat)abstract
    • The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)2) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.
  • Di Benedetto, Maria Domenica, et al. (författare)
  • Industrial control over wireless networks
  • 2010
  • Ingår i: International Journal of Robust and Nonlinear Control. - JOHN WILEY & SONS LTD. - 1049-8923. ; 20:2, s. 119-122
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Djurfeldt, Mikael, 1967-, et al. (författare)
  • Brain-scale simulation of the neocortex on the IBM Blue Gene/L  supercomputer
  • 2008
  • Ingår i: IBM Journal of Research and Development. - 0018-8646. ; 52:1-2, s. 31-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Biologically detailed large-scale models of the brain can now be simulated thanks to increasingly powerful massively parallel supercomputers. We present an overview, for the general technical reader, of a neuronal network model of layers II/III of the neocortex built with biophysical model neurons. These simulations, carried out on an IBM Blue Gene/Le supercomputer, comprise up to 22 million neurons and 11 billion synapses, which makes them the largest simulations of this type ever performed. Such model sizes correspond to the cortex of a small mammal. The SPLIT library, used for these simulations, runs on single-processor as well as massively parallel machines. Performance measurements show good scaling behavior on the Blue Gene/L supercomputer up to 8,192 processors. Several key phenomena seen in the living brain appear as emergent phenomena in the simulations. We discuss the role of this kind of model in neuroscience and note that full-scale models may be necessary to preserve natural dynamics. We also discuss the need for software tools for the specification of models as well as for analysis and visualization of output data. Combining models that range from abstract connectionist type to biophysically detailed will help us unravel the basic principles underlying neocortical function.
  • Egard, Mikael, et al. (författare)
  • Vertical InAs nanowire wrap gate transistors with f(t) > 7 GHz and f(max) > 20 GHz.
  • 2010
  • Ingår i: Nano Letters. - The American Chemical Society (ACS). - 1530-6992. ; 10:3, s. 809-812
  • Tidskriftsartikel (refereegranskat)abstract
    • In this letter we report on high-frequency measurements on vertically standing III-V nanowire wrap-gate MOSFETs (metal-oxide-semiconductor field-effect transistors). The nanowire transistors are fabricated from InAs nanowires that are epitaxially grown on a semi-insulating InP substrate. All three terminals of the MOSFETs are defined by wrap around contacts. This makes it possible to perform high-frequency measurements on the vertical InAs MOSFETs. We present S-parameter measurements performed on a matrix consisting of 70 InAs nanowire MOSFETs, which have a gate length of about 100 nm. The highest unity current gain cutoff frequency, f(t), extracted from these measurements is 7.4 GHz and the maximum frequency of oscillation, f(max), is higher than 20 GHz. This demonstrates that this is a viable technique for fabricating high-frequency integrated circuits consisting of vertical nanowires.
  • Engkvist, Josefin, et al. (författare)
  • Oxidation of FeCrAl foils at 500-900 degrees C in dry O-2 and O-2 with 40% H2O
  • 2009
  • Ingår i: Materials at High Temperatures. - 0960-3409. ; 26:2, s. 199-210
  • Tidskriftsartikel (refereegranskat)abstract
    • High temperature resistant FeCrAl alloys are frequently used in high temperature applications Such as heating elements and metal based catalytic converter bodies. When exposed to high temperatures an adherent, slowly growing, dense aluminium oxide layer forms on the surface, which protects the underlying alloy from severe degradation. The composition, structure and properties of the formed oxide layer are strongly dependent on the alloy composition, temperature and oxidation environment. In this study, the Sandvik 0C404 FeCrAl alloy, in the form of 50 mu m thick foils, was exposed isothermally in the temperature range 500-900 degrees C for 168 hours in dry O-2 and in O-2 with 40 vol.% H2O. The surface morphology, composition and microstructure of the grown oxide scales were characterized by using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), grazing incidence X-ray diffraction (GI-XRD), Auger electron spectroscopy (AES), and time of flight secondary ion mass spectrometry (TOF-SIMS). The oxidation process was faster at 900 degrees C than at 500 and 700 degrees C. At 500 degrees C a thin (10-20 nm) mixed oxide of Fe, Cr and Al was formed. Exposure at 700 degrees C resulted ill a similar (40-50 nm) duplex oxide, in both dry O-2 and in O-2 With 40 vol.% H2O. These oxide scales consisted of all inner and an outer relatively pure alumina separated by a Cr-rich band. This type of duplex oxide scale also formed at 900 degrees C with a thin inward growing alpha-Al2O3 at the oxide/metal interface and an outward growing layer outside a Cr-rich band. However, at 900 degrees C the Outward growing layer showed two types of oxide morphologies; a thin smooth base oxide and a much thicker nodular oxide grown on top of substrate ridges. In dry O-2 atmosphere, the main part of this outward growing layer had transformed to alpha-Al2O3. Only in the outer part of the thick oxide nodules, metastable alumina was found. When exposed in the presence of water vapour the main pall of the metastable alumina remained untransformed.
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