| 1. |
- 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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| 2. |
- 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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| 3. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 4. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 5. |
- Chao, Sui, et al.
(författare)
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Accidents Analysis and Safety Enhancement Methods : Based on Provincial Highway S213 (from Guanling County to Xingren County) in Guizhou Province
- 2013
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Ingår i: Proceedings of the 16th International Conference Road Safety on Four Continents. - Linköping : Statens väg- och transportforskningsinstitut.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Recently highway safety issues are more increasingly concerned by people and government because of the increasing accidents and developing highway traffic. Highway safety enhancement project is being launched in most provinces in China. This paper introduces the ways of doing highway safety enhancement project in China. It aims to analyse some accidents happened on provincial highway S213 in Guizhou province in China, then the reasons of them will be given and the composite safety enhancement method will also be shown in this paper.
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| 6. |
- Chen, Chao, et al.
(författare)
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Effects of Salt Tracer Amount, Concentration and Kind on the Fluid Flow Behavior in a Hydrodynamic Model of Continuous Casting Tundish
- 2012
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Ingår i: Steel Research International. - : John Wiley & Sons. - 1611-3683 .- 1869-344X. ; 83:12, s. 1141-1151
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Tidskriftsartikel (refereegranskat)abstract
- The hydrodynamic modeling method that widely used to simulate the fluid flow was reconsidered and discussed in this paper. The effects of injected salt tracer amount, concentration and kind on the fluid flow behavior in a hydrodynamic model tundish were investigated. The results were compared with the mathematical modeling calculation results, that the tracer density effect was eliminated. The residence time distribution (RTD) curve of tracer introduced deviated to the left side of the calculated curve, besides the deviation was increased as dimensionless tracer amount (the ratio of tracer amount to hydrodynamic model tundish volume) increased from 0.202 × 10−3 to 1.008 × 10−3. The results of tracer concentration study were similar, namely the deviation was increased with concentration increased; on the other hand, the deformation of a “stair-shape” RTD curve occurred when tracer concentration was much lower (at dimensionless tracer amount of 0.168 × 10−3 with converting to saturated solution). Besides, the effect of tracer kind on the accuracy of hydrodynamic modeling was also studied; the measurements of KCl solution with lower density than that of NaCl solution exhibited more of accuracy. Finally, the optimized tracer in hydrodynamic model tundish of present work is saturated KCl solution with dimensionless tracer amount of 0.202 × 10−3.
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| 7. |
- Chen, Hua, et al.
(författare)
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Analytic smoothness effect of solutions for spatially homogeneous Landau equation
- 2010
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Ingår i: Journal of Differential Equations. - : Elsevier BV. - 0022-0396. ; 248:1, s. 77-94
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we study the smoothness effect of Cauchy problem for the spatially homogeneous Landau equation in the hard potential case and theMaxwellian molecules case. We obtain the analytic smoothing effect for the solutions under rather weak assumptions on the initial datum.
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| 8. |
- Chen, Hua, et al.
(författare)
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Gevrey hypoellipticity for a class of kinetic equations
- 2011
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Ingår i: Communications in Partial Differential Equations. - : Informa UK Limited. - 0360-5302 .- 1532-4133. ; 36:4, s. 693-728
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we study the Gevrey regularity of weak solutions for a class of linear and semi-linear kinetic equations, which are the linear model of spatially inhomogeneous Boltzmann equations without an angular cutoff
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| 9. |
- Chen, Hua, et al.
(författare)
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Gevrey regularity of subelliptic Monge-Ampère equations in the plane
- 2011
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Ingår i: Advances in Mathematics. - : Elsevier BV. - 0001-8708. ; 228:3, s. 1816-1841
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we establish the Gevrey regularity of solutions for a class of degenerate Monge–Ampère equations in the plane. Under the assumptions that one principal entry of the Hessian is strictly positive and the coefficient of the equation is degenerate with appropriately finite type degeneracy, we prove that the solution of the degenerate Monge–Ampère equation will be smooth in Gevrey classes.
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| 10. |
- Chen, Jiguang, et al.
(författare)
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FEA of helmet-head injury protection based on motorcycle accident reconstruction
- 2013
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Ingår i: Proceedings - 2013 5th Conference on Measuring Technology and Mechatronics Automation, ICMTMA 2013. - 9780769549323 ; , s. 570-573
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Konferensbidrag (refereegranskat)abstract
- Head impact usually causes fatalities of riders in motorcycle accidents. The use of helmet can protect head effectively and the study of head injury mechanism is useful in safety helmet design and head injury risk decrease. A real motorcycle-passenger car accident was reconstructed in order to simulate and analyze the motion, impact velocity, impact angle in the collision. In order to study the dynamic response of helmeted head during the accident impact processing, an effective helmet model was constructed and validated. Coupling with the finite element model of human head, the injury mechanism of head and relevant parameters of biomechanics were studied and the protection ability of helmet was analyzed. It was found that the presence of helmet reduces the probility of head injury.
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