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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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4. |
- Chen, Jie, et al.
(author)
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Northwestward shift of the northern boundary of the East Asian summer monsoon during the mid-Holocene caused by orbital forcing and vegetation feedbacks
- 2021
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 268
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Journal article (peer-reviewed)abstract
- The East Asian summer monsoon (EASM) northern boundary is a critical indicator of EASM variations. Movement of the boundary is modulated by both the EASM and the mid-latitude westerlies. Here, we use the Earth system model EC-Earth to quantify the contribution of orbital forcing and vegetation feedbacks in modulating the movement of EASM northern boundary. The results show that the simulated EASM northern boundary during the mid-Holocene shifts by a maximum of ∼213 km northwestward due to orbital forcing. When the model was coupled with a dynamic vegetation module LPJ-GUESS, the northern boundary shifts further northwestward by a maximum of ∼90 km, indicating the importance of vegetation feedbacks. During the mid-Holocene, temperature increased in the mid-latitude during the boreal summer due to insolation, leading to increased meridional air temperature differences (MTDs) over the region north of 45°N and to decreased MTDs to the south. The changes in the temperature gradient weakened the East Asian Westly Jet (EAWJ) and displaced it northward, resulting in an earlier transition of the Meiyu stage and a more prolonged Midsummer stage. The northward movement of EAWJ, combined with the enhanced southerly moisture flow from South China, caused more precipitation in North China and eventually to a northwestward shift of the northern boundary of the EASM. The coupled dynamic vegetation module LPJ-GUESS simulated more grassland and less forest over Northeast Asia during the mid-Holocene. The increased surface albedo tended to lower the temperature in the region, and further enhanced the MTDs in mid-latitude East Asia, leading to the further northward movement of the EAWJ and a northwestward shift of the EASM northern boundary. Although the simulated vegetation distribution in several regions may be not accurate, it reflects the substantial contribution of climate-vegetation interaction on modulating the EASM.
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- Shao, Yue, et al.
(author)
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All-Poly(ionic liquid) Membrane-Derived Porous Carbon Membranes : Scalable Synthesis and Application for Photothermal Conversion in Seawater Desalination
- 2018
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 12:11, s. 11704-11710
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Journal article (peer-reviewed)abstract
- Herein, we introduce a straightforward, scalable, and technologically relevant strategy to manufacture charged porous polymer membranes (CPMs) in a controllable manner. The pore sizes and porous architectures of CPMs are well-controlled by rational choice of anions in poly(ionic liquid)s (PILs). Continuously, heteroatom-doped hierarchically porous carbon membrane (HCMs) can be readily fabricated via morphology-maintaining carbonization of as-prepared CPMs. These HCMs, as photothermal membranes, exhibited excellent performance for solar seawater desalination, representing a promising strategy to construct advanced functional nanomaterials for portable water production technologies.
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6. |
- Bai, Sai, et al.
(author)
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Reproducible Planar Heterojunction Solar Cells Based on One-Step Solution-Processed Methylammonium Lead Halide Perovskites
- 2017
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In: Chemistry of Materials. - : AMER CHEMICAL SOC. - 0897-4756 .- 1520-5002. ; 29:1, s. 462-473
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Journal article (peer-reviewed)abstract
- Metal halide perovskites have been demonstrated as one of the most promising materials for low-cost and high-performance photovoltaic applications. However, due to the susceptible crystallization process of perovskite films on planar substrates and the high sensitivity of the physical and optoelectronic nature of the internal interfaces within the devices, researchers in different laboratories still experience poor reproducibility in fabricating efficient perovskite solar cells with planar heterojunction device structures. In this method paper, we present detailed information on the reagents, equipment, and procedures for the fabrication of planar perovskite solar cells in both "regular" n-i-p and "inverted" p-i-n architectures based on one-step solution-processed methylammonium lead triiodide (MAPbI(3)) perovskite films. We discuss key parameters affecting the crystallization of perovskite and the device interfaces. This method paper will provide a guideline for the reproducible fabrication of planar heterojunction solar cells based on MAPbI3 perovskite films. We believe that the shared experience on MA-based perovskite films and planar solar cells will be also useful for the optimization process of perovskites with varied compositions, and other emerging perovskite-based optoelectronic devices.
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- Eriksson, Kristina M., 1976-, et al.
(author)
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Conceptual framework of scheduling applying discrete event simulation as an environment for deep reinforcement learning
- 2022
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In: Procedia CIRP. - : Elsevier BV. - 2212-8271 .- 2212-8271. ; 107, s. 955-960
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Journal article (peer-reviewed)abstract
- Increased environmental awareness is driving the manufacturing industry towards novel ways of energy reduction to become sustainable yet stay competitive. Climate and enviromental challenges put high priority on incorporating aspects of sustainability into both strategic and operational levels, such as production scheduling, in the manufacturing industry. Considering energy as a parameter when planning makes an already existing highly complex task of production scheduling even more multifaceted. The focus in this study is on inverse scheduling, defined as the problem of finding the number of jobs and duration times to meet a fixed input capacity. The purpose of this study was to investigate how scheduling can be formulated, within the environment of discrete event simulation coupled with reinforcement learning, to meet production demands while simultaneously minimize makespan and reduce energy. The study applied the method of modeling a production robot cell with its uncertainties, using discrete event simulation combined with deep reinforcement learning and trained agents. The researched scheduling approach derived solutions that take into consideration the performance measures of energy use. The method was applied and tested in a simulation environment with data from a real robot production cell. The study revealed opportunities for novel approaches of studying and reducing energy in the manufacturing industry. Results demonstrated a move towards a more holistic approach for production scheduling, which includes energy usage, that can aid decision-making and facilitate increased sustainability in production. We propose a conceptual framework for scheduling for minimizing energy use applying discrete event simulation as an environment for deep reinforcement learning.
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8. |
- Kist, Andreas M., et al.
(author)
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SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:9
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Journal article (peer-reviewed)abstract
- Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by micro-neurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p. M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p. M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences.
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9. |
- Shen, Zhaoyan, et al.
(author)
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A Multiagent Reinforcement Learning-Assisted Cache Cleaning Scheme for DM-SMR
- 2023
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In: IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0278-0070 .- 1937-4151. ; 42:8, s. 2500-2513
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Journal article (peer-reviewed)abstract
- To support nonsequential writes, persistent cache (PC) is constructed in drive managed SMR (DM-SMR) drive. However, PC cleaning introduces drastic performance degradation and enlarges tail latencies. In this article, we propose to utilize reinforcement learning (RL) to mitigate the longtail latency of PC cleaning. Our scheme uses the lightweight Q-learning method to monitor and learn the idle time of I/O workloads, based on which PC cleaning is intelligently guided, thus maximally exploit idle time between requests and hiding tail latency from normal requests. In addition, a multiagent RL scheme with clustering algorithm is adopted to further mitigate the tail latencies and adapt to variable workloads. We emulate a DM-SMR drive inside a Linux device driver to implement our proposed scheme. According to the experimental results, our scheme can effectively reduce the tail latency by 59.45% at the 99.9th percentile and the average latency by 48.75% compared with a typical shingled magnetic recording (SMR) design.
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10. |
- Wang, Di, et al.
(author)
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Soil water infiltration characteristics of reforested areas in the paleo-periglacial eastern Liaoning mountainous regions, China
- 2024
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In: Catena. - 0341-8162. ; 234
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Journal article (peer-reviewed)abstract
- Plantation forests (PF) and natural secondary forests (NSF) are the primary reforestation approaches. The establishment of PF can affect forest hydrological processes by changing soil structure. To date, few studies have focused on these changes and the effects on hydrological processes for the paleo-periglacial landform. To reveal reforestation approaches effects on water infiltration, including soil water infiltration capacity, retention capacity, and waterflow path pattern, we conducted field dye-tracer investigations with rainfall and laboratory infiltration experiments for the paleo-periglacial landform of eastern Liaoning mountains, China. The results showed that (1) Soil physical properties (including total porosity (TP), capillary porosity (CP), non-capillary porosity (NCP), initial soil water content (IWC), field water capacity (FWC)) and root abundance (RA) decreased with soil depth in both PF and NSF, while the soil bulk density (BD) and distribution of gravel content showed opposite changes. (2) Establishment of PF reduced the infiltration capacity and water retention capacity in the 0–20 cm layer, but enhanced the water retention capacity in 20–30 cm layer. Low IWC was conducive to increase soil water content (SWC) after infiltration. (3) Infiltration capacity parameters (including saturated hydraulic conductivity (Ks), SWC, difference between SWC and IWC (SWC–IWC), dye coverage ratio (DC)) were significantly correlated with BD, TP, CP, NCP, FWC, and fine roots RA (P < 0.05). Better connectivity gravels were more conducive to water infiltration. (4) Preferential flow was the main infiltration type, but with different waterflow paths pattern, with the 'funnel', 'finger' shape for PF, NSF, respectively. Increasing infiltration could increase flow path connectivity. Our findings show that soil physical properties, roots, and gravel occurrence affected soil infiltration, and different reforestation approaches had varying impacts on soil infiltration, water redistribution, transportation, and storage of surface and groundwater, improving the understanding of ecohydrological processes and effects of water resources management in forest ecosystems of paleo-periglacial landform.
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