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- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- Smedby, Karin E., et al.
(författare)
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GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:4, s. e1001378-
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, P-combined= 2x10(-21)) located 962 bp away from rs10484561 (r(2)< 0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012: ORadjusted = 0.70, P-adjusted= 4x10(-12); rs10484561: ORadjusted = 1.64, P-adjusted= 5x10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, P-combined = 1.4x10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.
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- Fischer, P., et al.
(författare)
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A new control scheme for an HVDC transmission link with capacitor-commutated converters having the inverter operating with constant alternating voltage
- 2012
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Ingår i: 44th International Conference on Large High Voltage Electric Systems 2012. ; , s. 1-11
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Konferensbidrag (refereegranskat)abstract
- Experience and theoretical analysis show that the voltage and power stability becomes an important issue when high-voltage direct current (HVDC) systems using line-commutated converters (LCC) are connected to AC systems with low short-circuit capacity and that these problems become more pronounced the lower the short-circuit capacity of the connected AC system is, as compared with the rating of the HVDC converter station. Normally some additional equipment, like static or synchronous compensators, will be installed in order to improve the performance of the HVDC transmission system, when it is connected to a weak AC system. The cost of the substation thereby will be increased. The Capacitor-Commutated Converter (CCC), which has been developed by ABB, offers an alternative to the LCC in this kind of application. It reduces the reactive power interaction between the converter and the connected AC system. The CCC is, in principle, a classical converter provided with a series capacitor placed between the converter valves and the converter transformer. In this paper a new control strategy that can be used together with such a CCC is presented. In the new control system the inverter emulates the operation of a Voltage Source Converter, in the sense that, beside the control of the active power flow through the converter, the reactive power exchange with the AC network can also be managed in order to adjust the alternating voltage of the converter bus. Studies have shown that the interaction between the inverter and the connected AC system is significantly reduced, when the CCC is used together with this new control strategy. Keeping the alternating voltage constant makes it possible to control the DC-side voltage of the HVDC transmission system, allowing the rectifier converter to control the active power by means of controlling the direct current. This combination allows stable operation of the HVDC transmission system even under severe network conditions associated with low short-circuit power in the connected AC network at the inverter side. In the paper it is shown that, with the new control scheme, it is possible to operate the inverter into an almost passive AC network (a network with very few rotating generators, resulting in almost no short circuit power). Simulation results have indicated satisfactory operation of the HVDC transmission with the inverter operating into a network having a Short-Circuit Ratio as low as 0.2 (SCR ≈ 0.2). To the knowledge of the authors, operation of a line-commutated converter at such low SCR values has never been reported previously. A description of the new control scheme will be presented. The calculated performance in a practically implemented installation, the Rio Madeira Back-to-Back system, will be illustrated.
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- Liakos, Evangelos, et al.
(författare)
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Benefits of implementing a duty-ratio controlled parallel-resonant converter with SiC MOSFETs instead of Si IGBTs
- 2021
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Ingår i: 2021 23rd European Conference on Power Electronics and Applications, EPE 2021 ECCE Europe. - : IEEE. - 9789075815375
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Konferensbidrag (refereegranskat)abstract
- In this paper, the operation of a parallel resonant converter with a capacitive output filter that exploits the parasitic components of its transformer is described briefly. Measurements from a high power DC pulsed generator with Si IGBTs are obtained. Finally, the experimentally calculated losses of the Si IGBTs are compared with SiC MOSFETs' losses using simulations of the system. © 2021 EPE Association.
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- Nee, Hans-Peter, et al.
(författare)
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Determination of d and q reactances of permanent-magnet synchronous motors without measurements of the rotor position
- 2000
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Ingår i: IEEE transactions on industry applications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0093-9994 .- 1939-9367. ; 36:5, s. 1330-1335
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Tidskriftsartikel (refereegranskat)abstract
- The interest in permanent-magnet synchronous motors:(PMSMs) is increasing in a wide area of applications. Since most PMSMs will operate without a shaft sensor in the future, valuable: information for experimental determination of machine parameters will be lost,In this paper, therefore, a method is presented where the induced EMF and the d-axis reactance are determined in a no-load test and the q-axis reactance is determined in a load test. The load angle delta is determined from the load test by means of a new analytical method. In this way, no separate measurement of the load angle is required. The method is especially suitable for line-start PMSMs which normally operate with negative d-axis current and, therefore, are not saturated in the d-axis flux paths. Moreover, the method is very simple to carry out for any laboratory technician, since the only tests that have to be made are standard tests which are made on standard induction motors on a regular basis.
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