| 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. |
- Cheng, Qin-Bo, et al.
(författare)
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Improvement and comparison of likelihood functions for model calibration and parameter uncertainty analysis within a Markov chain Monte Carlo scheme
- 2014
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 519:Part B, s. 2202-2214
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Tidskriftsartikel (refereegranskat)abstract
- Summary In this study, the likelihood functions for uncertainty analysis of hydrological models are compared and improved through the following steps: (1) the equivalent relationship between the Nash–Sutcliffe Efficiency coefficient (NSE) and the likelihood function with Gaussian independent and identically distributed residuals is proved; (2) a new estimation method of the Box–Cox transformation (BC) parameter is developed to improve the effective elimination of the heteroscedasticity of model residuals; and (3) three likelihood functions—NSE, Generalized Error Distribution with BC (BC-GED) and Skew Generalized Error Distribution with BC (BC-SGED)—are applied for SWAT-WB-VSA (Soil and Water Assessment Tool – Water Balance – Variable Source Area) model calibration in the Baocun watershed, Eastern China. Performances of calibrated models are compared using the observed river discharges and groundwater levels. The result shows that the minimum variance constraint can effectively estimate the BC parameter. The form of the likelihood function significantly impacts on the calibrated parameters and the simulated results of high and low flow components. SWAT-WB-VSA with the NSE approach simulates flood well, but baseflow badly owing to the assumption of Gaussian error distribution, where the probability of the large error is low, but the small error around zero approximates equiprobability. By contrast, SWAT-WB-VSA with the BC-GED or BC-SGED approach mimics baseflow well, which is proved in the groundwater level simulation. The assumption of skewness of the error distribution may be unnecessary, because all the results of the BC-SGED approach are nearly the same as those of the BC-GED approach.
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| 3. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 4. |
- Lanata, Nicola, et al.
(författare)
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Efficient implementation of the Gutzwiller variational method
- 2012
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121. ; 85:3
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Tidskriftsartikel (refereegranskat)abstract
- We present a self-consistent numerical approach to solve the Gutzwiller variational problem for general multi-band models with arbitrary on-site interaction. The proposed method generalizes and improves the procedure derived by Deng et al., Phys. Rev. B. 79 075114 (2009), overcoming the restriction to density-density interaction without increasing the complexity of the computational algorithm. Our approach drastically reduces the problem of the high-dimensional Gutzwiller mini- mization by mapping it to a minimization only in the variational density matrix, in the spirit of the Levy and Lieb formulation of DFT. For fixed density the Gutzwiller renormalization matrix is deter- mined as a fixpoint of a proper functional, whose evaluation only requires ground-state calculations of matrices defined in the Gutzwiller variational space. Furthermore, the proposed method is able to account for the symmetries of the variational function in a controlled way, reducing the number of variational parameters. After a detailed description of the method we present calculations for multi-band Hubbard models with full (rotationally invariant) Hund’s rule on-site interaction. Our analysis shows that the numerical algorithm is very efficient, stable and easy to implement. For these reasons this method is particularly suitable for first principle studies – e.g., in combination with DFT – of many complex real materials, where the full intra-atomic interaction is important to obtain correct results.
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| 5. |
- Xi, Bo, et al.
(författare)
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Hypertension Screening Using Blood Pressure to Height Ratio
- 2014
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 134:1, s. E106-E111
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The definition of hypertension in children is too complex to be used by medical professionals and children and their parents because of the age-, gender-, and height-specific blood pressure (BP) algorithm. The aim of this study was to simplify the pediatric BP percentile references using BP to height ratio (BPHR, equal to BP/height) for screening for prehypertension and hypertension in Chinese children. METHODS: Data were obtained from the China Health and Nutrition Survey, which was conducted from 1991 to 2009 and included 11 661 children aged 6 to 17 years with complete data on age, gender, height, and BP values. Receiver operating characteristic curve analysis was performed to assess the performance of systolic BPHR (SBPHR) and diastolic BPHR (DBPHR) for screening for pediatric prehypertension and hypertension. RESULTS: The optimal thresholds for defining prehypertension were 0.81 in children aged 6 to 11 years and 0.70 in adolescents aged 12 to 17 years for SBPHR and 0.52 in children and 0.46 in adolescents for DBPHR, respectively. The corresponding values for hypertension were 0.84, 0.78, 0.55, and 0.50, respectively. The negative predictive values were much higher (all >= 99%) for prehypertension and hypertension, although the positive predictive values were relatively lower, ranging from 13% to 75%. CONCLUSIONS: BPHR index is simple and accurate for screening for prehypertension and hypertension in Chinese children aged 6 to 17 years and can be used for early screening or treating Chinese children with hypertension.
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| 6. |
- Yin, Bo, et al.
(författare)
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Glucose esters as biobased PVC plasticizers
- 2014
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Ingår i: European Polymer Journal. - : Elsevier BV. - 0014-3057 .- 1873-1945. ; 58, s. 34-40
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Tidskriftsartikel (refereegranskat)abstract
- Utilization of glucose, produced by liquefaction of cellulose or other abundant biomass sources, as raw material for production of green plasticizers would offer an attractive alternative to traditional phthalate plasticizers. Three glucose hexanoate esters (GHs) were synthesized by one-step reaction and evaluated as green plasticizers for poly(vinyl chloride) (PVC). The esterification was carried out for three different time periods to obtain plasticizers with different number of hexanoate groups, as the degree of substitution could influence the miscibility between PVC and GHs. A fast and powerful laser desorption ionization-mass spectrometry (LDI-MS) method was developed to obtain molecular level structural information of the plasticizer structures. All the GHs showed good miscibility with PVC and the GH blends exhibited better mechanical properties, in the form of higher strain at break and lower modulus, as compared to glucose pentaacetate (GPA) and sucrose octaacetate (SOA) blends that were studied in comparison. Altogether the results indicate that the synthesized glucose esters have large potential as green PVC plasticizers and they could be a promising option to overcome the environmental problems caused by phthalate plasticizers.
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