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- 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. |
- Zhou, Xian-Jing, et al.
(författare)
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Thermo-sensitive Microgels Supported Gold Nanoparticles as Temperature-mediated Catalyst
- 2019
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Ingår i: Chinese Journal of Polymer Science. - : Springer Science and Business Media LLC. - 0256-7679 .- 1439-6203. ; 37:3, s. 235-242
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Tidskriftsartikel (refereegranskat)abstract
- Microgels with a thermo-sensitive poly(N-isopropylacrylamide) (polyNIPAm) backbone and bis-imidazolium (VIM) ionic cross-links, denoted as poly(NIPAm-co-VIM), were successfully prepared. The as-synthesized ionic microgels were converted to nanoreactors, denoted as Au@PNI MGs, upon generation and immobilization of gold nanoparticles (Au NPs) of 5-8 nm in size into poly(NIPAm-co-VIM). The content of Au NPs in microgels could be regulated by controlling the 1,6-dibromohexane/vinylimidazole molar ratio in the quaternization reaction. The microgel-based nanoreactors were morphologically spherical and uniform in size, and presented reversible thermo-sensitive behavior with volume phase transition temperatures (VPTTs) at 39-40 degrees C. The Au@PNI MGs were used for the reduction of 4-nitrophenol, of which the catalytic activity could be modulated by temperature.
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| 7. |
- Cai, Baoping, et al.
(författare)
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Application of Bayesian Networks in Reliability Evaluation
- 2019
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Ingår i: IEEE Transactions on Industrial Informatics. - : IEEE. - 1551-3203 .- 1941-0050. ; 15:4, s. 2146-2157
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Tidskriftsartikel (refereegranskat)abstract
- The Bayesian network (BN) is a powerful model for probabilistic knowledge representation and inference and is increasingly used in the field of reliability evaluation. This paper presents a bibliographic review of BNs that have been proposed for reliability evaluation in the last decades. Studies are classified from the perspective of the objects of reliability evaluation, i.e., hardware, structures, software, and humans. For each classification, the construction and validation of a BN-based reliability model are emphasized. The general procedural steps for BN-based reliability evaluation, including BN structure modeling, BN parameter modeling, BN inference, and model verification and validation, are investigated. Current gaps and challenges in reliability evaluation with BNs are explored, and a few upcoming research directions that are of interest to reliability researchers are identified.
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| 8. |
- Dou, Jin-Hu, et al.
(författare)
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Atomically precise single-crystal structures of electrically conducting 2D metal-organic frameworks
- 2021
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Ingår i: Nature Materials. - : Springer Science and Business Media LLC. - 1476-1122 .- 1476-4660. ; 20, s. 222-228
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Tidskriftsartikel (refereegranskat)abstract
- Electrically conducting 2D metal-organic frameworks (MOFs) have attracted considerable interest, as their hexagonal 2D lattices mimic graphite and other 2D van der Waals stacked materials. However, understanding their intrinsic properties remains a challenge because their crystals are too small or of too poor quality for crystal structure determination. Here, we report atomically precise structures of a family of 2D pi-conjugated MOFs derived from large single crystals of sizes up to 200 mu m, allowing atomic-resolution analysis by a battery of high-resolution diffraction techniques. A designed ligand core rebalances the in-plane and out-of-plane interactions that define anisotropic crystal growth. We report two crystal structure types exhibiting analogous 2D honeycomb-like sheets but distinct packing modes and pore contents. Single-crystal electrical transport measurements distinctively demonstrate anisotropic transport normal and parallel to the pi-conjugated sheets, revealing a clear correlation between absolute conductivity and the nature of the metal cation and 2D sheet packing motif. Two-dimensional MOFs can possess porosity and electrical conductivity but are difficult to grow as single crystals. Here, by balancing in-plane and out-of-plane interactions, single crystals of sizes up to 200 mu m are grown, allowing in-plane transport measurements and atomic-resolution analysis.
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| 9. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 10. |
- Gu, Qiang, et al.
(författare)
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VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China
- 2010
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 66:12, s. 1217-1227
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Tidskriftsartikel (refereegranskat)abstract
- There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.
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