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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. |
- Xiang, Yusen, et al.
(författare)
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Ginkgolic acids inhibit SARS-CoV-2 and its variants by blocking the spike protein/ACE2 interplay
- 2023
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier. - 0141-8130 .- 1879-0003. ; 226, s. 780-792
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Tidskriftsartikel (refereegranskat)abstract
- Targeting the interaction between the spike protein receptor binding domain (S-RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2) is a potential therapeutic strategy for treating coronavirus disease 2019 (COVID-19). However, we still lack small-molecule drug candidates for this target due to the missing knowledge in the hot spots for the protein-protein interaction. Here, we used NanoBiT technology to identify three Ginkgolic acids from an in-house traditional Chinese medicine (TCM) library, and they interfere with the S-RBD/ACE2 interplay. Our pseudovirus assay showed that one of the compounds, Ginkgolic acid C17:1 (GA171), significantly inhibits the entry of original SARS-CoV-2 and its variants into the ACE2-overexpressed HEK293T cells. We investigated and proposed the binding sites of GA171 on S-RBD by combining molecular docking and molecular dynamics simulations. Site-directed mutagenesis and surface plasmon resonance revealed that GA171 specifically binds to the pocket near R403 and Y505, critical residues of S-RBD for S-RBD interacting with ACE2. Thus, we provide structural insights into developing new small-molecule inhibitors and vaccines against the proposed S-RBD binding site.
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| 4. |
- Yao, Tandong, et al.
(författare)
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Recent Third Pole’s rapid warming accompanies cryospheric melt and water cycle intensification and interactions between monsoon and environment: multi-disciplinary approach with observation, modeling and analysis
- 2019
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Ingår i: Bulletin of The American Meteorological Society. - 0003-0007 .- 1520-0477. ; :March, s. 423-444
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Tidskriftsartikel (refereegranskat)abstract
- The Third Pole (TP) is experiencing rapid warming and is currently in its warmest period in the past 2,000 years. This paper reviews the latest development in multidisciplinary TP research associated with this warming. The rapid warming facilitates intense and broad glacier melt over most of the TP, although some glaciers in the northwest are advancing. By heating the atmosphere and reducing snow/ice albedo, aerosols also contribute to the glaciers melting. Glacier melt is accompanied by lake expansion and intensification of the water cycle over the TP. Precipitation has increased over the eastern and northwestern TP. Meanwhile, the TP is greening and most regions are experiencing advancing phenological trends, although over the southwest there is a spring phenological delay mainly in response to the recent decline in spring precipitation. Atmospheric and terrestrial thermal and dynamical processes over the TP affect the Asian monsoon at different scales. Recent evidence indicates substantial roles that mesoscale convective systems play in the TP’s precipitation as well as an association between soil moisture anomalies in the TP and the Indian monsoon. Moreover, an increase in geohazard events has been associated with recent environmental changes, some of which have had catastrophic consequences caused by glacial lake outbursts and landslides. Active debris flows are growing in both frequency of occurrences and spatial scale. Meanwhile, new types of disasters, such as the twin ice avalanches in Ali in 2016, are now appearing in the region. Adaptation and mitigation measures should be taken to help societies’ preparation for future environmental challenges. Some key issues for future TP studies are also discussed.
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| 5. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 6. |
- Chen, Fengxiang, et al.
(författare)
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Adaptive chaos synchronization based on LMI technique
- 2007
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Ingår i: Physica Scripta. - : IOP Publishing. - 0031-8949 .- 1402-4896. ; 75:3, s. 285-288
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Tidskriftsartikel (refereegranskat)abstract
- The paper investigates the robust synchronization for two identical uncertain chaotic systems with different parameters perturbation and external disturbances. Based on Lyapunov stability theory, linear matrix inequality (LMI) techniques and adaptive techniques, a novel controller is proposed. With the resulting controller, global asymptotical synchronization between two identical uncertain chaotic systems is achieved. Finally, a Lorenz system is given as an example to verify the effectiveness of the proposed controller.
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| 7. |
- Chen, Fengxiang, et al.
(författare)
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Robust control of chaos in the Lorenz system with the variable structure control approach
- 2008
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Ingår i: Physica scripta. T. - : IOP Publishing. - 0281-1847 .- 0031-8949 .- 1402-4896. ; 77:2
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper is concerned with the robust control for a class of the uncertain Lorenz system subject to sector nonlinear input. Based on rigorous mathematical analysis, the proposed variable structure controller can drive the system state exactly to a class of a specific point or in the predictable neighborhood of an arbitrary desired point in the state space even with mismatch uncertainties. Moreover, the controller ensures that one of the error components can approach zero as time approaches infinity. Finally, numerical simulation results show the effectiveness of our work.
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| 8. |
- Chen, Fengxiang, et al.
(författare)
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Stabilization of parameters perturbation chaotic system via adaptive backstepping technique
- 2008
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Ingår i: Applied Mathematics and Computation. - : Elsevier BV. - 0096-3003 .- 1873-5649. ; 200:1, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- The work of Yassen [M.T. Yassen, Chaos control of chaotic dynamical systems using backstepping design, Chaos Soliton Fract. 27 (2006) 537-548] which mainly investigated the stabilization problem for a class of chaotic systems without the parameters perturbation. This paper is concerned with stabilization problem for a class of parameters perturbation chaotic systems via both backstepping design method and adaptive technique. The proposed controllers can guarantee that the parameters perturbation systems will be stabilized at a fixed bounded point. Furthermore, the paper also proposes controllers to stabilize the uncertain chaotic system at equilibrium point with only backstepping design method. Finally, numerical simulations are given to illustrate the effectiveness of the proposed controllers
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| 9. |
- Liao, Guangdong, et al.
(författare)
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Multi-Infection Patterns and Co-infection Preference of 27 Human Papillomavirus Types Among 137,943 Gynecological Outpatients Across China
- 2020
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: The epidemiological feature of human papillomavirus (HPV) infection is distinctive in China. We aimed to investigate the multi-infection patterns and co-infection preference of 27 HPV types among gynecological outpatients across China. Methods: Overall 137,943 gynecological outpatients were recruited from eight tertiary hospitals located in seven regions of China, between July 1st, 2014 and December 31st, 2016. The overall, region-specific, age-specific and type-specific prevalence of HPV infection were calculated, respectively. The pattern of HPV infection was also evaluated. Furthermore, rate ratio was calculated to evaluate the co-infection preference of any two HPV genotypes. Results: The overall prevalence of 27 HPVs' [17 high-risk (hr)/10 low-risk (lr)] infection was 23.5%. The age-specific HPV prevalence showed a "U-shaped" pattern. The most prevalent hrHPV genotypes were 16, 52, and 58. Multiple infections were detected in 25.8% of the HPV-positive women, in which dual infection was more prevalent. HPV 16/18 were likely to co-infected with HPV 31 but unlikely with HPV 52/58, i.e., the co-infection of HPV 16 with HPV 31 was high (3.5-fold), but low for HPV 58 (1.8-fold), and 52 (1.2-fold), while the co-infection of HPV 18 with HPV 31 was high (4.3-fold), but low for HPV 52 (1.9-fold), and 58 (1.7-fold). Conclusions: We found age-specific prevalence of HPV infection showed a "U-shaped" pattern for high and low risk HPV, suggesting the importance of screening among younger women and the necessary of detection among older women. We found a novel co-infection preference of HPV 16/18 with 31, 52, and 58, suggesting a need of developing and marketing prophylactic HPV vaccines that protect against more genotypes in China.
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| 10. |
- Pan, Jiaxin, et al.
(författare)
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Operando dynamics of trapped carriers in perovskite solar cells observed via infrared optical activation spectroscopy
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Conventional spectroscopies are not sufficiently selective to comprehensively understand the behaviour of trapped carriers in perovskite solar cells, particularly under their working conditions. Here we use infrared optical activation spectroscopy (i.e., pump-push-photocurrent), to observe the properties and real-time dynamics of trapped carriers within operando perovskite solar cells. We compare behaviour differences of trapped holes in pristine and surface-passivated FA(0.99)Cs(0.01)PbI(3) devices using a combination of quasi-steady-state and nanosecond time-resolved pump-push-photocurrent, as well as kinetic and drift-diffusion models. We find a two-step trap-filling process: the rapid filling (similar to 10 ns) of low-density traps in the bulk of perovskite, followed by the slower filling (similar to 100 ns) of high-density traps at the perovskite/hole transport material interface. Surface passivation by n-octylammonium iodide dramatically reduces the number of trap states (similar to 50 times), improving the device performance substantially. Moreover, the activation energy (similar to 280 meV) of the dominant hole traps remains similar with and without surface passivation.
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