| 1. |
- Duggan, D., et al.
(författare)
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Two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene DAB2IP
- 2007
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 99:24, s. 1836-1844
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Tidskriftsartikel (refereegranskat)abstract
- Background: The consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. These variants could be useful in screening and treatment. Methods: We performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in Sweden. We combined the results of this scan with those for aggressive prostate cancer from the publicly available Cancer Genetic Markers of Susceptibility (CGEMS) Study. Single-nucleotide polymorphisms (SNPs) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of European or African American descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. Results: Among the approximately 60000 SNPs that were common to our study and CGEMS, we identified seven that had a similar (positive or negative) and statistically significant (P<.01) association with the risk of aggressive prostate cancer in both studies. Analysis of the distribution of these SNPs among 1032 prostate cancer patients and 571 control subjects of European descent indicated that one, rs1571801, located in the DAB2IP gene, which encodes a novel Ras GTPase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided P value =. 004). The association was also statistically significant in an African American study population that included 210 prostate cancer patients and 346 control subjects (one-sided P value =. 02). Conclusion: A genetic variant in DAB2IP may be associated with the risk of aggressive prostate cancer and should be evaluated further.
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| 2. |
- Sun, J L, et al.
(författare)
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Interactions of sequence variants in interieukin-1 receptor-associated kinase4 and the Toll-like receptor 6-1-10 gene cluster increase prostate cancer risk
- 2006
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Umea Univ, Dept Radiat Sci, Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Univ Hosp Uppsala, Reg Oncol Ctr, Uppsala, Sweden. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD USA. : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 15:3, s. 480-485
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Tidskriftsartikel (refereegranskat)abstract
- Chronic or recurrent inflammation has been suggested as a causal factor in several human malignancies, including prostate cancer. Genetic predisposition is also a strong risk factor in the development of prostate cancer. In particular, Toll-like receptors (TLR), especially the TLR6-1-10 gene cluster, are involved in prostate cancer development. Interleukin-1 receptor-associated kinases (IRAK) 1 and 4 are critical components in the TLR signaling pathway. In this large case-control study, we tested two hypotheses: (a) sequence variants in IRAK1 and IRAK4 are associated with prostate cancer risk and (b) sequence variants in IRAK1/4 and TLR1-6-10 interacts and confers a stronger risk to prostate cancer. We analyzed 11 single nucleotide polymorphisms (four in IRAK1 and seven in IRAK4) among 1,383 newly diagnosed prostate cancer patients and 780 population controls in Sweden. Although the single-nucleotide polymorphisms in IRAK1 and IRAK4 alone were not significantly associated with prostate cancer risk, one single-nucleotide polymorphism in IRAK4, when combined with the high-risk genotype at TLR6-1-10, conferred a significant excess risk of prostate cancer. In particular, men with the risk genotype at TLR6-1-10 and IRAK4-7987 CG/CC had an odds ratio of 9.68 (P = 0.03) when compared with men who had wildtype genotypes. Our findings suggest synergistic effects between sequence variants in IRAK4 and the TLR 6-1-10 gene cluster. Although this study was based on a priori hypothesis and was designed to address many common issues facing this type of study, our results need confirmation in even larger studies.
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| 3. |
- Sun, J L, et al.
(författare)
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Sequence variants in toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk
- 2005
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Ingår i: Journal of the National Cancer Institute. - Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA. Umea Univ, Dept Radiat Sci & Oncol, Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Univ Uppsala Hosp, Reg Oncol Ctr, Uppsala, Sweden. Johns Hopkins Sch Med, Dept Urol, Baltimore, MD USA. : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 97:7, s. 525-532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic inflammation plays an important role in several human cancers and may be involved in the etiology of prostate cancer. Toll-like receptors (TLRs) are important in the innate immune response to pathogens and in cross-talk between innate immunity and adaptive immunity. Our previous finding of an association of TLR4 gene sequence variants and prostate cancer risk provides evidence for a role of TLRs in prostate cancer. In this study, we investigated whether sequence variants in the TLR6-TLR1-TLR10 gene cluster, residing within a 54-kb region on 4p14, were associated with prostate cancer risk. Methods: We selected 32 single-nucleotide polymorphisms (SNPs) covering these three genes and genotyped these SNPs in 96 control subjects from the Cancer Prostate in Sweden (CAPS) population-based prostate cancer case-control study. Five distinct haplotype blocks were inferred at this region, and we identified 17 haplotype-tagging SNPs (htSNPs) that could uniquely describe < 95% of the haplotypes. These 17 htSNPs were then genotyped in the entire CAPS study population (1383 case subjects and 780 control subjects). Odds ratios of prostate cancer for the carriers of a variant allele versus those with the wild-type allele were estimated using unconditional logistic regression. Results: The allele frequencies of 11 of the 17 SNPs were statistically significantly different between case and control subjects (P = .04-.001), with odds ratios for variant allele carriers (homozygous or heterozygous) compared with wild-type allele carriers ranging from 1.20 (95% confidence interval [CI] = 1.00 to 1.43) to 1.38 (95% CI = 1.12 to 1.70). Phylogenetic tree analyses of common haplotypes identified a clade of two evolutionarily related haplotypes that are statistically significantly associated with prostate cancer risk. These two haplotypes contain all the risk alleles of these 11 associated SNPs. Conclusion: The observed multiple associated SNPs at the TLR6-TLR1-TLR10 gene cluster were dependent and suggest the presence of a founder prostate cancer risk variant on this haplotype background. The TLR6-TLR1-TLR10 gene cluster may play a role in prostate cancer risk, although further functional studies are needed to pinpoint the disease-associated variants in this gene cluster.
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| 4. |
- Lindmark, F, et al.
(författare)
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H6D polymorphism in macrophage-inhibitory cytokine-1 gene associated with prostate cancer
- 2004
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Ingår i: Journal of the National Cancer Institute. - Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Umea Univ Hosp, Dept Urol & Androl, S-90185 Umea, Sweden. Wake Forest Univ, Sch Med, Ctr Human Genomics, Winston Salem, NC 27109 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 96:16, s. 1248-1254
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accumulating epidemiologic and molecular evidence suggest that inflammation is an important component in the etiology of prostate cancer. Macrophage-inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor beta superfamily, is thought to play an important role in inflammation by regulating macrophage activity. We examined whether sequence variants in the MIC-1 gene are associated with the risk of prostate cancer. Methods: The study population, a population-based case-control study in Sweden, consisted of 1383 prostate cancer case patients and 780 control subjects. From 94 of the control subjects, we constructed gene-specific haplotypes of MIC-1 and identified four haplotype-tagging single-nucleotide polymorphisms (SNPs): Exon1+25 (V9L), Exon1+142 (S48T), IVS1+1809, and Exon2+2423 (H6D). All study subjects were genotyped for the four SNPs, and conditional logistic regression analysis was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: A statistically significant difference (P = .006) in genotype frequency was observed for the nonsynonymous change H6D) (histidine to aspartic acid at position 6) between prostate cancer patients and control subjects. Carriers of the GC genotype, which results in the H6D change, experienced a lower risk of sporadic prostate cancer (OR = 0.80, 95% CI = 0.66 to 0.97) and of familial prostate cancer (OR = 0.61, 95% CI = 0.42 to 0.89) than the CC genotype carriers. In the study population, the proportion of prostate cancer cases attributable to the CC genotype was 7.2% for sporadic cancer and 19.2% for familial cancer. None of the other SNPs or haplotypes was associated with prostate cancer. Conclusion: This study shows an association between a nonsynonymous change (H6D) in the MIC-1 gene and prostate cancer. This finding supports the hypothesis that genetic variation in the inflammatory process contributes to prostate cancer susceptibility.
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| 5. |
- Bao, Z., et al.
(författare)
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An optimal charging scheduling model and algorithm for electric buses
- 2023
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Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 332
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Tidskriftsartikel (refereegranskat)abstract
- Electrification poses a promising low-carbon or even zero-carbon transportation solution, serving as a strategic approach to reducing carbon emissions and promoting carbon neutrality in the transportation sector. Along the transportation electrification pathway, the goal of carbon neutrality can be further accelerated with an increasing amount of electricity being generated from renewable energies. The past decade observed the rapid development of battery technologies and deployment of electricity infrastructure worldwide, fostering transportation electrification to expand from railways to light and then heavy vehicles on roadways. In China, a massive number of electric buses have been employed and operated in dozens of metropolises. An important daily operations issue with these urban electric buses is how to coordinate their charging activities in a cost-effective manner, considering various physical, financial, institutional, and managerial constraints. This paper addresses a general charging scheduling problem for an electric bus fleet operated across multiple bus lines and charging depots and terminals, aiming at finding an optimal set of charging location and time decisions given the available charging windows. The charging windows for each bus are predetermined in terms of its layovers at depots and terminals and each of them is discretized into a number of charging slots with the same time duration. A mixed linear integer programming model with binary charging slot choice and continuous state-of-charge (SOC) variables is constructed for minimizing the total charging cost of the bus fleet subject to individual electricity consumption rates, electricity charging rates, time-based charging windows, battery SOC bounds, time-of-use (TOU) charging tariffs, and station-specific electricity load capacities. A Lagrangian relaxation framework is employed to decouple the joint charging schedule of a bus fleet into a number of independent single-bus charging schedules, which can be efficiently addressed by a bi-criterion dynamic programming algorithm. A real-world regional electric bus fleet of 122 buses in Shanghai, China is selected for validating the effectiveness and practicability of the proposed charging scheduling model and algorithm. The optimization results numerically reveal the impacts of TOU tariffs, station load capacities, charging infrastructure configurations, and battery capacities on the bus system performance as well as individual recharging behaviors, and justify the superior solution efficiency of our algorithm against a state-of-the-art commercial solver.
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| 6. |
- Brown, David A, et al.
(författare)
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Macrophage inhibitory cytokine 1 : a new prognostic marker in prostate cancer.
- 2009
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 15:21, s. 6658-6664
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis. EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years). RESULTS: MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis. CONCLUSIONS: Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis.
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| 7. |
- Gao, Y., et al.
(författare)
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Cooling pitch cabinets in wind turbines using a pulsating heat pipe : A case study
- 2023
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Ingår i: Case Studies in Thermal Engineering. - : Elsevier Ltd. - 2214-157X. ; 50
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Tidskriftsartikel (refereegranskat)abstract
- As the electric capacity of wind turbine increases, heat dissipation in pitch cabinets becomes challenging owing to the limited space and rotating conditions. To cool down the pitch cabinet more effectively and allow heat dissipation, we designed and implemented a pulsating heat pipe (PHP) in this study. We designed PHP parameters and conducted performance tests to compare the cooling performance of the fabricated PHP with that of an air-based cooling system in a 1.5 MW wind turbine. The results demonstrated steady PHP operation under rotating conditions (17.3 rpm). At a heat load of 1000 W, the evaporator outlet temperature was only 76.1 °C. However, increasing the ambient temperature adversely affected PHP operation, resulting in higher temperature and thermal resistance. The heat-pipe-based cooling system lowered the insulated gate bipolar transistor (IGBT) temperature by about 20.4 °C in relation to the air-based cooling system, while being suitable under varied conditions. Additionally, the system could successfully operate when the heat load of IGBT was 2350 W, corresponding to a 7 MW electric capacity of the wind turbine. Reducing the manufacturing cost of the heat pipe would further enhance the applicability of this system for pitch cabinet IGBT cooling, such as decreasing payback period.
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| 8. |
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| 9. |
- Lindmark, F, et al.
(författare)
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Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk
- 2005
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Ingår i: British Journal of Cancer. - Umea Univ, Dept Radiat Sci Oncol, S-90187 Umea, Sweden. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Univ Hosp, Reg Oncol Ctr, Uppsala, Sweden. : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 93:4, s. 493-497
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Tidskriftsartikel (refereegranskat)abstract
- IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1 alpha and IL1 beta. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case - control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms ( SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe 495% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) ( haplotype-specific P = 0.009). Evaluation of the prostate cancer risk associated with carrying the 'ATGC' haplotype revealed that homozygous carriers were at significantly increased risk ( odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2 - 2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype ( OR = 1.0, 95% CI = 0.8 - 1.2). Restricting analyses to advanced prostate cancer strengthened the association between the 'ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI = 1.3 - 2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association.
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| 10. |
- Lindström, Sara, et al.
(författare)
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Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk : strong confirmation of functional promoter SNP
- 2005
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Ingår i: Human Genetics. - Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Karolinska Inst, Ctr Genom & Bioinformat, Stockholm, Sweden. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD USA. CLINTECH, Karolinska Inst, Ctr Oncol, Stockholm, Sweden. : SPRINGER. - 0340-6717 .- 1432-1203. ; 118:3-4, s. 339-347
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Tidskriftsartikel (refereegranskat)abstract
- The E-cadherin gene (CDH1) has been proposed as a prostate cancer (PC) susceptibility gene in several studies. Aberrant protein expression has been related to prognosis and progression in PC. In addition, a functional promoter SNP (rsl6260) has been found to associate with PC risk. We performed a comprehensive genetic analysis of CDH1 by using the method of haplotype tagged SNPs in a large Swedish population-based case-control study consisting of 801 controls and 1,636 cases. In addition, Swedish PC families comprising a total of 157 cases sampled for DNA were analyzed for selected SNPs. Seven SNPs, including the promoter SNP rsl6260, that captured over 96% of CDH1 haplotype variation were selected as haplotype tagging SNPs and analyzed for associated PC risk. We observed significant confirmation of rsl6260 (P=0.003) for cases with a positive family history of PC (FH+) both in an independent case-control population and in PC families. In addition, a common haplotype (HapB, 25%) including the variant allele of rsl6260 was associated (P=0.004) with PC risk among FH+ cases. The promoter SNP rsl6260 as well as HapB were significantly transmitted to affected offspring in PC families. We report strong confirmation of the association between PC risk in FH+ cases and a functional CDH1 promoter SNP in an independent population. In conjunction with the biological importance of CDH1 our findings encourage further evaluation of genetic variation in CDH1 in relation to PC etiology. Due to the difficulties in replication of genetic association studies. this finding is unusual and novel.
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