| 1. |
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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. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 4. |
- Holleboom, Adriaan G, et al.
(författare)
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Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man
- 2011
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Ingår i: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 14:6, s. 811-8
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGalNAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene.
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| 5. |
- Dubrovinsky, Leonid, et al.
(författare)
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Materials synthesis at terapascal static pressures
- 2022
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Ingår i: Nature. - London, United Kingdom : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 605:7909, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- Theoretical modelling predicts very unusual structures and properties of materials at extreme pressure and temperature conditions(1,2). Hitherto, their synthesis and investigation above 200 gigapascals have been hindered both by the technical complexity of ultrahigh-pressure experiments and by the absence of relevant in situ methods of materials analysis. Here we report on a methodology developed to enable experiments at static compression in the terapascal regime with laser heating. We apply this method to realize pressures of about 600 and 900 gigapascals in a laser-heated double-stage diamond anvil cell(3), producing a rhenium-nitrogen alloy and achieving the synthesis of rhenium nitride Re7N3-which, as our theoretical analysis shows, is only stable under extreme compression. Full chemical and structural characterization of the materials, realized using synchrotron single-crystal X-ray diffraction on microcrystals in situ, demonstrates the capabilities of the methodology to extend high-pressure crystallography to the terapascal regime.
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| 6. |
- Aslandukov, Andrey, et al.
(författare)
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Anionic N18 Macrocycles and a Polynitrogen Double Helix in Novel Yttrium Polynitrides YN6 and Y2N11 at 100 GPa
- 2022
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Ingår i: Angewandte Chemie International Edition. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 1433-7851 .- 1521-3773. ; 61:34
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Tidskriftsartikel (refereegranskat)abstract
- Two novel yttrium nitrides, YN6 and Y2N11, were synthesized by direct reaction between yttrium and nitrogen at 100 GPa and 3000 K in a laser-heated diamond anvil cell. High-pressure synchrotron single-crystal X-ray diffraction revealed that the crystal structures of YN6 and Y2N11 feature a unique organization of nitrogen atoms-a previously unknown anionic N-18 macrocycle and a polynitrogen double helix, respectively. Density functional theory calculations, confirming the dynamical stability of the YN6 and Y2N11 compounds, show an anion-driven metallicity, explaining the unusual bond orders in the polynitrogen units. As the charge state of the polynitrogen double helix in Y2N11 is different from that previously found in Hf2N11 and because N-18 macrocycles have never been predicted or observed, their discovery significantly extends the chemistry of polynitrides.
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| 7. |
- Aslandukov, Andrey, et al.
(författare)
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Synthesis of LaCN3, TbCN3, CeCN5, and TbCN5 Polycarbonitrides at Megabar Pressures
- 2024
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Ingår i: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 146:26, s. 18161-18171
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic ternary metal-C-N compounds with covalently bonded C-N anions encompass important classes of solids such as cyanides and carbodiimides, well known at ambient conditions and composed of [CN](-) and [CN2](2-) anions, as well as the high-pressure formed guanidinates featuring [CN3](5-) anion. At still higher pressures, carbon is expected to be 4-fold coordinated by nitrogen atoms, but hitherto, such CN4-built anions are missing. In this study, four polycarbonitride compounds (LaCN3, TbCN3, CeCN5, and TbCN5) are synthesized in laser-heated diamond anvil cells at pressures between 90 and 111 GPa. Synchrotron single-crystal X-ray diffraction (SCXRD) reveals that their crystal structures are built of a previously unobserved anionic single-bonded carbon-nitrogen three-dimensional (3D) framework consisting of CN4 tetrahedra connected via di- or oligo-nitrogen linkers. A crystal-chemical analysis demonstrates that these polycarbonitride compounds have similarities to lanthanide silicon phosphides. Decompression experiments reveal the existence of LaCN3 and CeCN5 compounds over a very large pressure range. Density functional theory (DFT) supports these discoveries and provides further insight into the stability and physical properties of the synthesized compounds.
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| 8. |
- Basner, Mathias, et al.
(författare)
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ICBEN Review of Research on the Biological Effects of Noise 2011-2014
- 2015
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Ingår i: Noise & Health. - : Medknow. - 1463-1741 .- 1998-4030. ; 17:75, s. 57-82
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Forskningsöversikt (refereegranskat)abstract
- The mandate of the International Commission on Biological Effects of Noise (ICBEN) is to promote a high level of scientific research concerning all aspects of noise-induced effects on human beings and animals. In this review, ICBEN team chairs and co-chairs summarize relevant findings, publications, developments, and policies related to the biological effects of noise, with a focus on the period 2011-2014 and for the following topics: Noise-induced hearing loss; nonauditory effects of noise; effects of noise on performance and behavior; effects of noise on sleep; community response to noise; and interactions with other agents and contextual factors. Occupational settings and transport have been identified as the most prominent sources of noise that affect health. These reviews demonstrate that noise is a prevalent and often underestimated threat for both auditory and nonauditory health and that strategies for the prevention of noise and its associated negative health consequences are needed to promote public health.
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| 9. |
- Datta-Chaudhuri, Timir, et al.
(författare)
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The Fourth Bioelectronic Medicine Summit "Technology Targeting Molecular Mechanisms" : current progress, challenges, and charting the future
- 2021
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Ingår i: Bioelectronic medicine. - : BioMed Central. - 2332-8886. ; 7:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is a broad and growing interest in Bioelectronic Medicine, a dynamic field that continues to generate new approaches in disease treatment. The fourth bioelectronic medicine summit "Technology targeting molecular mechanisms" took place on September 23 and 24, 2020. This virtual meeting was hosted by the Feinstein Institutes for Medical Research, Northwell Health. The summit called international attention to Bioelectronic Medicine as a platform for new developments in science, technology, and healthcare. The meeting was an arena for exchanging new ideas and seeding potential collaborations involving teams in academia and industry. The summit provided a forum for leaders in the field to discuss current progress, challenges, and future developments in Bioelectronic Medicine. The main topics discussed at the summit are outlined here.
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| 10. |
- Di Marzo, Marcela A. D., et al.
(författare)
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Computational Tool for Aircraft Fuel System Analysis
- 2024
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Ingår i: AEROSPACE. - : MDPI. - 2226-4310. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Fuel level gauging in aircraft presents a significant flight mechanics challenge due to the influence of aircraft movements on measurements. Moreover, it constitutes a multidimensional problem where various sensors distributed within the tank must converge to yield a precise and single measurement, independent of the aircraft's attitude. Furthermore, fuel distribution across multiple tanks of irregular geometries complicates the readings even further. These issues critically impact safety and economy, as gauging errors may compromise flight security and lead to carrying excess weight. In response to these challenges, this research introduces a multi-stage project in aircraft fuel gauging systems, as a continuum of studies, where this first article presents a computational tool designed to simulate aircraft fuel sensor data readings as a function of fuel level, fuel tank geometry, sensor location, and aircraft attitude. Developed in an open-source environment, the tool aims to support the statistical inference required for accurate modeling in which synthetic data generation becomes a crucial component. A discretization procedure accurately maps fuel tank geometries and their mass properties. The tool, then, intersects these geometries with fuel-level planes and calculates each new volume. It integrates descriptive geometry to intersect these fuel planes with representative capacitive level-sensing probes and computes the sensor readings for the simulated flight conditions. The method is validated against geometries with analytical solutions. This process yields detailed fuel measurement responses for each sensor inside the tank, and for different analyzed fuel levels, providing insights into the sensors' signals' non-linear behavior at each analyzed aircraft attitude. The non-linear behavior is also influenced by the sensor saturation readings at 0 when above the fuel level and at 1 when submerged. The synthetic fuel sensor readings lay the baseline for a better understanding on how to compute the true fuel level from multiple sensor readings, and ultimately optimizing the amount of used sensors and their placement. The tool's design offers significant improvements in aircraft fuel gauging accuracy, directly impacting aerostructures and instrumentation, and it is a key aspect of flight safety, fuel management, and navigation in aerospace technology.
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