| 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. |
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| 3. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Chu, Ming, et al.
(författare)
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Accurate capacitance-voltage characterization of organic thin films with current injection*
- 2021
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Ingår i: Chinese Physics B. - : IOP PUBLISHING LTD. - 1674-1056. ; 30:8
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Tidskriftsartikel (refereegranskat)abstract
- To deal with the invalidation of commonly employed series model and parallel model in capacitance-voltage (C-V) characterization of organic thin films when current injection is significant, a three-element equivalent circuit model is proposed. On this basis, the expression of real capacitance in consideration of current injection is theoretically derived by small-signal analysis method. The validity of the proposed equivalent circuit and theoretical expression are verified by a simulating circuit consisting of a capacitor, a diode, and a resistor. Moreover, the accurate C-V characteristic of an organic thin film device is obtained via theoretical correction of the experimental measuring result, and the real capacitance is 35.7% higher than the directly measured capacitance at 5-V bias in the parallel mode. This work strongly demonstrates the necessity to consider current injection in C-V measurement and provides a strategy for accurate C-V characterization experimentally.
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| 5. |
- Álvarez-Muñiz, Jaime, et al.
(författare)
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The Giant Radio Array for Neutrino Detection (GRAND) : Science and design
- 2020
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Ingår i: Science China Physics, Mechanics & Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 63:1
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Forskningsöversikt (refereegranskat)abstract
- The Giant Radio Array for Neutrino Detection (GRAND) is a planned large-scale observatory of ultra-high-energy (UHE) cosmic particles, with energies exceeding 108 GeV. Its goal is to solve the long-standing mystery of the origin of UHE cosmic rays. To do this, GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched sensitivity. GRAND will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the atmosphere. Its design is modular: 20 separate, independent sub-arrays, each of 10000 radio antennas deployed over 10000 km(2). A staged construction plan will validate key detection techniques while achieving important science goals early. Here we present the science goals, detection strategy, preliminary design, performance goals, and construction plans for GRAND.
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| 6. |
- Amin, Ridwanul, et al.
(författare)
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Healthcare use before and after suicide attempt in refugees and Swedish-born individuals
- 2021
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer. - 0933-7954 .- 1433-9285. ; 56:2, s. 325-338
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: There is a lack of research on whether healthcare use before and after a suicide attempt differs between refugees and the host population. We aimed to investigate if the patterns of specialised (inpatient and specialised outpatient) psychiatric and somatic healthcare use, 3 years before and after a suicide attempt, differ between refugees and the Swedish-born individuals in Sweden. Additionally, we aimed to explore if specialised healthcare use differed among refugee suicide attempters according to their sex, age, education or receipt of disability pension.METHODS: All refugees and Swedish-born individuals, 20-64 years of age, treated for suicide attempt in specialised healthcare during 2004-2013 (n = 85,771 suicide attempters, of which 4.5% refugees) were followed 3 years before and after (Y - 3 to Y + 3) the index suicide attempt (t0) regarding their specialised healthcare use. Annual adjusted prevalence with 95% confidence intervals (CIs) of specialised healthcare use were assessed by generalized estimating equations (GEE). Additionally, in analyses among the refugees, GEE models were stratified by sex, age, educational level and disability pension.RESULTS: Compared to Swedish-born, refugees had lower prevalence rates of psychiatric and somatic healthcare use during the observation period. During Y + 1, 25% (95% CI 23-28%) refugees and 30% (95% CI 29-30%) Swedish-born used inpatient psychiatric healthcare. Among refugees, a higher specialised healthcare use was observed in disability pension recipients than non-recipients.CONCLUSION: Refugees used less specialised healthcare, before and after a suicide attempt, relative to the Swedish-born. Strengthened cultural competence among healthcare professionals and better health literacy among the refugees may improve healthcare access in refugees.
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| 7. |
- Amin, Ridwanul, et al.
(författare)
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Suicide attempt and suicide in refugees in Sweden - a nationwide population-based cohort study
- 2021
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 51:2, s. 254-263
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite a reported high rate of mental disorders in refugees, scientific knowledge on their risk of suicide attempt and suicide is scarce. We aimed to investigate (1) the risk of suicide attempt and suicide in refugees in Sweden, according to their country of birth, compared with Swedish-born individuals and (2) to what extent time period effects, socio-demographics, labour market marginalisation (LMM) and morbidity explain these associations.METHODS: Three cohorts comprising the entire population of Sweden, 16-64 years at 31 December 1999, 2004 and 2009 (around 5 million each, of which 3.3-5.0% refugees), were followed for 4 years each through register linkage. Additionally, the 2004 cohort was followed for 9 years, to allow analyses by refugees' country of birth. Crude and multivariate hazard ratios (HRs) with 95% confidence intervals (CIs) were computed. The multivariate models were adjusted for socio-demographic, LMM and morbidity factors.RESULTS: In multivariate analyses, HRs regarding suicide attempt and suicide in refugees, compared with Swedish-born, ranged from 0.38-1.25 and 0.16-1.20 according to country of birth, respectively. Results were either non-significant or showed lower risks for refugees. Exceptions were refugees from Iran (HR 1.25; 95% CI 1.14-1.41) for suicide attempt. The risk for suicide attempt in refugees compared with the Swedish-born diminished slightly across time periods.CONCLUSIONS: Refugees seem to be protected from suicide attempt and suicide relative to Swedish-born, which calls for more studies to disentangle underlying risk and protective factors.
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| 8. |
- Amin, Ridwanul, et al.
(författare)
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Trajectories of antidepressant use before and after a suicide attempt among refugees and Swedish-born individuals : a cohort study
- 2021
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Ingår i: International Journal for Equity in Health. - : BioMed Central. - 1475-9276. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To identify key information regarding potential treatment differences in refugees and the host population, we aimed to investigate patterns (trajectories) of antidepressant use during 3 years before and after a suicide attempt in refugees, compared with Swedish-born. Association of the identified trajectory groups with individual characteristics were also investigated.METHODS: All 20-64-years-old refugees and Swedish-born individuals having specialised healthcare for suicide attempt during 2009-2015 (n = 62,442, 5.6% refugees) were followed 3 years before and after the index attempt. Trajectories of annual defined daily doses (DDDs) of antidepressants were analysed using group-based trajectory models. Associations between the identified trajectory groups and different covariates were estimated by chi2-tests and multinomial logistic regression.RESULTS: Among the four identified trajectory groups, antidepressant use was constantly low (≤15 DDDs) for 64.9% of refugees. A 'low increasing' group comprised 5.9% of refugees (60-260 annual DDDs before and 510-685 DDDs after index attempt). Two other trajectory groups had constant use at medium (110-190 DDDs) and high (630-765 DDDs) levels (22.5 and 6.6% of refugees, respectively). Method of suicide attempt and any use of psychotropic drugs during the year before index attempt discriminated between refugees' trajectory groups. The patterns and composition of the trajectory groups and their association, discriminated with different covariates, were fairly similar among refugees and Swedish-born, with the exception of previous hypnotic and sedative drug use being more important in refugees.CONCLUSIONS: Despite previous reports on refugees being undertreated regarding psychiatric healthcare, no major differences in antidepressant treatment between refugees and Swedish-born suicide attempters were found.
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| 9. |
- 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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| 10. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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