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| 2. |
- 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. |
- Abdulla, Parosh, Professor, 1961-, et al.
(author)
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On the State Reachability Problem for Concurrent Programs Under Power
- 2020
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In: Networked Systems - 8th International Conference, {NETYS} 2020, Morocco, Revised Selected Papers. - : Springer Nature Switzerland AG.
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Conference paper (peer-reviewed)abstract
- We consider the problem of safety verification, formalized as control-state reachability, for concurrent programs running on the Power architecture. Our main result shows that safety verification under Power is undecidable for programs with just two threads.
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| 4. |
- Abecasis, David, et al.
(author)
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A review of acoustic telemetry in Europe and the need for a regional aquatic telemetry network
- 2018
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In: Animal Biotelemetry. - : Springer. - 2050-3385. ; 6
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Journal article (peer-reviewed)abstract
- Background: Globally, there are a large and growing number of researchers using biotelemetry as a tool to studyaquatic animals. In Europe, this community lacks a formal network structure. The aim of this study is to review the useof acoustic telemetry in Europe and document the contribution of cross-boundary studies and inter-research groupcollaborations. Based on this, we explore the potential benefits and challenges of a network approach to identifyfuture priorities and best practices for aquatic biotelemetry research in Europe.Results: Over the past decade, there was an approximately sevenfold increase in the number of acoustic telemetrystudies published on marine and diadromous species in Europe compared to a sixfold increase globally. Over 90%of these studies were conducted on fishes and undertaken in coastal areas, estuaries, or rivers. 75% of these studieswere conducted by researchers based in one of five nations (Norway, UK, France, Portugal, and Spain) and, eventhough 34% were based on collaborations between scientists from several countries, there was only one study withan acoustic receiver array that extended beyond the borders of a single country. In recent years, acoustic telemetryin European waters has evolved from studying behavioural aspects of animals (82.2%), into more holistic approachesaddressing management-related issues (10%), tagging methods and effects (5%), and technology and data analysisdevelopment (2.8%).Conclusions: Despite the increasing number of publications and species tracked, there is a prominent lack ofplanned and structured acoustic telemetry collaborations in Europe. A formal pan-European network structure wouldpromote the development of (1) a research platform that could benefit the acoustic telemetry community throughcapacity building, (2) a centralized database, and (3) key deployment sites and studies on priority species requiringresearch in Europe. A network may increase efficiency, expand the scope of research that can be undertaken, promoteEuropean science integration, enhance the opportunities and success of acquiring research funding and, ultimately,foster regional and transatlantic collaborations. It may also help address research priorities such as the large-scalesocietal challenges arising from climate change impacts and assist the EU’s Marine Strategy Framework Directive viaidentification of good environmental status of endangered or commercially important species.
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| 5. |
- Alnaes, Dag, et al.
(author)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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In: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Journal article (peer-reviewed)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 7. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)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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| 8. |
- Berne, Olivier, et al.
(author)
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PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
- 2022
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In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
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Journal article (peer-reviewed)abstract
- Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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| 9. |
- Björnstig, Ulf, et al.
(author)
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Tågolyckan på Once station, Buenos Aires 2012
- 2019
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Reports (other academic/artistic)abstract
- Händelsen: Tågolyckan inträffade på morgonen den 22 februari 2012 när ett lokaltåg okontrollerat körde in i stoppanordningen i slutet av perrongen på Once station, i centrala Buenos Aires. Hastigheten var mellan 20 och 27 km i timmen, men stoppet var så kraftigt att vagn nummer två trängde sex meter in i vagn nummer ett. Sammanlagt skadades cirka 850 personer varav 51 avled, de flesta omkom i samband med att de två första vagnarna klämdes ihop. Bidragande faktorer till att så många skadades var, ett överfullt tåg av äldre modell, som var dåligt underhållet, och kördes av en organisation med låg säkerhetsmedvetenhet. Händelsen visar att en masskadesituation kan uppstå även vid låga hastigheter. Räddningsinsatsen var omfattande: ett hundratal ambulanser, tre helikoptrar och mer än 500 räddningsarbetare engagerades för att omhänderta skadade och fördela dem mellan huvudstadens 13 akutsjukhus. Beredskapen i Buenos Aires var god vid denna händelse, tack vare genomförda risk- och sårbarhetsanalyser, övningar och utbildningsinsatser. Den argentinska akutmedicinska responsorganisationen och sjukhusen arbetade i stor utsträckning enligt samma katastrofmedicinska principer som i Sverige. Händelsen kunde därför analyseras utifrån ett svenskt perspektiv.Erfarenheter: Sverige har varit relativt förskonat från tågolyckor med många svårt skadade. Däremot har tillbuden ökat kraftigt och järnvägssystemet är idag slitet och överbelastat. Det finns därför anledning att studera inträffade tågolyckor i världen för att dra lärdom av internationella erfarenheter av olika skadebegränsande faktorer som kan vara av betydelse för svensk katastrofmedicinsk beredskap. Det går att dra flera lärdomar ifrån tågolyckan på Once-stationen.Nedan redovisas ett antal sammanfattande slutsatser från händelsen med relevans för den svenska beredskapen:• Det finns en risk att händelser med många svårt skadade kan inträffa även vid låga hastigheter.• Tågens konstruktion, utformningen av koppel och deformationszoner, samt materielens förslitningsgrad är av stor betydelse för säkerheten.• Risken att passagerare, bagage och lösa föremål kastas runt i tågvagnen vid en häftig inbromsning är påtaglig.• Buffertstopp som är konstruerade så att de ger upphov till ett abrupt stopp, utgör en riskfaktor för allvarliga deformationsförlopp och skador, även vid låga hastigheter. TÅGOLYCKAN PÅ ONCE STATION, BUENOS AIRES 2012 SOCIALSTYRELSEN 9• Brister i företags och myndigheters kvalitetssäkring av sin verksamhet bidrar till att risken för händelser som tågolyckan på Once-stationen inträffar.• Varningar om tekniska fel som inte tas på allvar i organisationens säkerhetsarbete utgör en riskfaktor.• Bristande träning bland räddningspersonal i de räddningstekniska svårigheter som kan uppstå vid en tågolycka, till exempel att ta loss fastklämda, kan bidra till att hantering av drabbade fördröjs.• Förmågan att bedöma situationen och prioritera bland de drabbade i samråd med medicinskt ansvarig kan sannolikt vara av stor betydelse för att minska insatstiden till de svårast klämda och skadade.• Samtliga sjukhus bör ha en i förväg fastställd förmåga att ta emot patienter vid förstärknings- respektive katastrofläge, så att särskild sjukvårdsledning på regional nivå har möjlighet att snabbt fördela ett stort antal skadade.• En väl fungerande plan för krisstöd och samlad anhörigupplysning underlättar för den somatiska vården. Brister i en sådan plan får stora konsekvenser för allmänhetens förtroende.• För att hantera en lika stor tågolycka i Sverige kan flera regioner behöva engageras, vilket ställer stora krav på ledningsförmågan i den drabbade regionen. Dessutom behövs en effektiv samverkan mellan lokal, regional och nationell nivå. Det är därför nödvändigt med en gemensam nationell ledningsmodell vid särskild händelse, gemensamma kris- och katastrofmedicinska utbildningar och regelbundna övningar.
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