| 11. |
|
|
| 12. |
|
|
| 13. |
- Harris, Valerie M., et al.
(författare)
-
Klinefelters syndrome (47,XXY) is in excess among men with Sjogrens syndrome
- 2016
-
Ingår i: Clinical Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1521-6616 .- 1521-7035. ; 168, s. 25-29
-
Tidskriftsartikel (refereegranskat)abstract
- Primary Sjogrens syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelters syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47)0(Y, p = 0.0012 by Fishers exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fishers exact test p = NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA. Published by Elsevier Inc.
|
|
| 14. |
- Haycock, Philip C., et al.
(författare)
-
Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
-
Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
-
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.
|
|
| 15. |
- Hu, Gang, et al.
(författare)
-
CMRLCCOA: Multi-Strategy Enhanced Coati Optimization Algorithm for Engineering Designs and Hypersonic Vehicle Path Planning
- 2024
-
Ingår i: Biomimetics. - : MDPI. - 2313-7673. ; 9:7
-
Tidskriftsartikel (refereegranskat)abstract
- The recently introduced coati optimization algorithm suffers from drawbacks such as slow search velocity and weak optimization precision. An enhanced coati optimization algorithm called CMRLCCOA is proposed. Firstly, the Sine chaotic mapping function is used to initialize the CMRLCCOA as a way to obtain better-quality coati populations and increase the diversity of the population. Secondly, the generated candidate solutions are updated again using the convex lens imaging reverse learning strategy to expand the search range. Thirdly, the L & eacute;vy flight strategy increases the search step size, expands the search range, and avoids the phenomenon of convergence too early. Finally, utilizing the crossover strategy can effectively reduce the search blind spots, making the search particles constantly close to the global optimum solution. The four strategies work together to enhance the efficiency of COA and to boost the precision and steadiness. The performance of CMRLCCOA is evaluated on CEC2017 and CEC2019. The superiority of CMRLCCOA is comprehensively demonstrated by comparing the output of CMRLCCOA with the previously submitted algorithms. Besides the results of iterative convergence curves, boxplots and a nonparametric statistical analysis illustrate that the CMRLCCOA is competitive, significantly improves the convergence accuracy, and well avoids local optimal solutions. Finally, the performance and usefulness of CMRLCCOA are proven through three engineering application problems. A mathematical model of the hypersonic vehicle cruise trajectory optimization problem is developed. The result of CMRLCCOA is less than other comparative algorithms and the shortest path length for this problem is obtained.
|
|
| 16. |
- Hu, Wenjun, et al.
(författare)
-
Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer
- 2019
-
Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), tumor cells can develop mechanisms to evade oxaliplatin-induced cell death and show high tolerance and acquired resistance to this drug. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) has been proved to play a critical role in DNA repair during IgH class switch recombination (CSR) in B lymphocytes, while, its role in CRC and chemotherapeutic resistance remain unknown. Our study aims to uncover an unidentified mechanism of regulating DNA double-strand breaks (DSBs) by hnRNP L in CRC cells treated by oxaliplatin. In present study, we observed that knockdown of hnRNP L enhanced the level of DNA breakage and sensitivity of CRC cells to oxaliplatin. The expression of key DNA repair factors (BRCA1, 53BP1, and ATM) was unaffected by hnRNP L knockdown, thereby excluding the likelihood of hnRNP L mediation via mRNA regulation. Moreover, we observed that phosphorylation level of ATM changed oppositely to 53BP1 and BRCA1 in the CRC cells (SW620 and HCT116) which exhibit synergistic effect by oxaliplatin plus hnRNP L impairment. And similar phenomenon was observed in the foci formation of these critical repair factors. We also found that hnRNP L binds directly with these DNA repair factors through its RNA-recognition motifs (RRMs). Analysis of cell death indicated that the RRMs of hnRNP L are required for cell survival under incubation with oxaliplatin. In conclusion, hnRNP L is critical for the recruitment of the DNA repair factors in oxaliplatin-induced DSBs. Targeting hnRNP L is a promising new clinical approach that could enhance the effectiveness of current chemotherapeutic treatment in patients with resistance to oxaliplatin.
|
|
| 17. |
- Ishigaki, Kazuyoshi, et al.
(författare)
-
Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:11, s. 1640-1651
-
Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10−8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.
|
|
| 18. |
- Iwnicki, Simon, et al.
(författare)
-
Advances in vehicle-track interaction tools
- 2009
-
Ingår i: Railway Gazette International. - 0373-5346. ; 165:9, s. 47-52
-
Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- In this article, the authors discuss how computer modeling is enabling researchers to improve their understanding of vehicle-track interaction. This in turn allows for more accurate predictions to be made regarding rail damage on plain lines as well as turn-outs. The authors discuss track interaction models, multi-body system modeling, surface roughness models, and train-turnout interactions. The article concludes with the authors noting that numerous parameters related to design and conditions influence dynamic train-turnout interactions.
|
|
| 19. |
- Kottyan, Leah C., et al.
(författare)
-
The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
-
Tidskriftsartikel (refereegranskat)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
|
|
| 20. |
- Li, Xing-Yu, et al.
(författare)
-
Comparative Study of Dayside Pulsating Auroras Induced by Ultralow-Frequency Waves
- 2023
-
Ingår i: Universe. - : MDPI AG. - 2218-1997. ; 9:6
-
Tidskriftsartikel (refereegranskat)abstract
- Pulsating auroras are usually observed with ultralow-frequency (ULF) waves in the Pc 3-5 band (period 10-600 s). These auroras are thought to result from interactions between energetic electrons and chorus waves, but their relationship with ULF waves remains an open question. In this study, we investigated this question by conducting a comparative study on two ULF wave events with pulsating auroras observed near the magnetic footprints. Conjugate observations from the Magnetospheric Multiscale mission and the Chinese Yellow River Station were used. In both events, lower-band chorus waves were observed, which were suggested to be connected with the auroral pulsations by wavelet analysis. The intensity of these waves oscillates at the period of the ULF waves, but the physics laid behind them differs by events. During the event of 22 January 2019, compressional ULF waves changed the threshold for the whistler anisotropy instability periodically, affecting the emission of chorus waves. In the event on 10 January 2016, poloidal ULF waves modulated the chorus wave generation by regulating electron temperature anisotropy through drift resonance. ULF waves in these events may originate from perturbations in the solar wind. We highlight the role of ULF waves in the solar wind-magnetosphere-ionosphere coupling, which requires further study.
|
|
