| 1. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Ding, Lianghui, et al.
(författare)
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Energy minimization in wireless multihop networks using two-way network coding
- 2011
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Ingår i: IEEE 73rd Vehicular Technology Conference (VTC-2011-Spring), Budapest, Ungern. - 9781424483310
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Konferensbidrag (refereegranskat)abstract
- The total energy minimization in wireless multihop networks using two-way network coding is investigated in this paper. The problem is first formulated as a linear programming problem, then decomposed into two sub-problems using the Lagrangian decomposition, and finally solved with the subgradient method. After that, the backpressure based algorithm is proposed to solve the problem in a distributed manner. The performance of the algorithm is evaluated first in a simple topology for analysis and then in a random topology with different number of flows for practical consideration. Simulation results show that the convergence time increases as the number of nodes in the network, and the energy cost per packet can be saved up to 30% by using two-way network coding.
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| 4. |
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| 5. |
- Ding, Liang-Hui, et al.
(författare)
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Lifetime maximization routing with network coding in wireless multihop networks
- 2013
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Ingår i: SCIENCE CHINA-INFORMATION SCIENCES. - : Springer Science and Business Media LLC. - 1674-733X .- 1869-1919. ; 56:2, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we consider the lifetime maximization routing with network coding in wireless multihop networks. We first show that lifetime maximization with network coding is different from pure routing, throughput maximization with network coding and energy minimization with network coding. Then we formulate lifetime maximization problems in three different cases of (i) no network coding, (ii) two-way network coding, and (iii) overhearing network coding. To solve these problems, we use flow augmenting routing (FA) for the first case, and then extend the FA with network coding (FANC) by using energy minimized one-hop network coding. After that, we investigate the influence of parameters of FANC, evaluate the performance of FANC with two-way and overhearing network coding schemes and compare it with that without network coding under two different power control models, namely, protocol and physical ones. The results show that the lifetime can be improved significantly by using network coding, and the performance gain of network coding decreases with the increase of flow asymmetry and the power control ability.
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| 6. |
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| 7. |
- He, Shu-Lan, et al.
(författare)
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Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.
- 2013
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Ingår i: Experimental Cell Research. - : Elsevier. - 0014-4827 .- 1090-2422. ; 319:17, s. 2604-2616
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Tidskriftsartikel (refereegranskat)abstract
- Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4 × 44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios ≥ 2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.
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| 8. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 9. |
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| 10. |
- Wang, Hao, et al.
(författare)
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A unified algorithm for mobility load balancing in 3GPP LTE multi-cell networks
- 2013
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Ingår i: Science in China. Series F, Information Sciences. - : Science China Press. - 1009-2757. ; 56
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Tidskriftsartikel (refereegranskat)abstract
- 3GPP long term evolution (LTE) is a promising candidate for the next-generation wireless network, which is expected to achieve high spectrum efficiency by using advanced physical layer techniques and flat network structures. However, the LTE network still faces the problem of load imbalance as in GSM/WCDMA networks, and this may cause significant deterioration of system performance. To deal with this problem, mobility load balancing (MLB) has been proposed as an important use case in 3GPP self-organizing network (SON), in which the serving cell of a user can be selected to achieve load balancing rather than act as the cell with the maximum received power. Furthermore, the LTE network aims to serve users with different quality-of-service (QoS) requirements, and the network-wide objective function for load balancing is distinct for different kinds of users. Thus, in this paper, a unified algorithm is proposed for MLB in the LTE network. The load balancing problem is first formulated as an optimization problem with the optimizing variables being cell-user connections. Then the complexity and overhead of the optimal solution is analyzed and a practical and distributed algorithm is given. After that, the proposed algorithm is evaluated for users with different kinds of QoS requirements, i.e., guaranteed bit rate (GBR) users with the objective function of load balance index and non-GBR (nGBR) users with the objective function of total utility, respectively. Simulation results show that the proposed algorithm leads to significantly balanced load distribution for GBR users to decrease the new call blocking rate, and for nGBR users to improve the cell-edge throughput at the cost of only slight deterioration of total throughput.
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