| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
- Barchyn, Thomas E., et al.
(författare)
-
Subglacial bed form morphology controlled by ice speed and sediment thickness
- 2016
-
Ingår i: Geophysical Research Letters. - 0094-8276. ; 43:14, s. 7572-7580
-
Tidskriftsartikel (refereegranskat)abstract
- Subglacial bed forms (drumlins, ribbed moraines, and megascale glacial lineations) are enigmatic repetitive flow-parallel and flow-transverse landforms common in glaciated landscapes. Their evolution and morphology are a potentially powerful constraint for ice sheet modeling, but there is little consensus on bed form dynamics or formative mechanisms. Here we explore shallow sediment bed form dynamics via a simple model that iterates (i) down-flow till flux, (ii) pressure gradient-driven till flux, and (iii) entrainment and deposition of sediment. Under various boundary conditions, replicas of subglacial bed forms readily emerge. Bed form dynamics mirror those in subaqueous and aeolian domains. Transitions between ribbed moraines and elongate flow-parallel bed forms are associated with increasing ice speeds and declining sediment thickness. These simulations provide quantitative flux estimates and suggest that widely observed transitions in shallow sediment subglacial bed forms (e.g., ribbed moraines to drumlinoids to megascale glacial lineations) are manifestations of subtle variations in ice velocity and sediment thickness.
|
|
| 3. |
- Cable, Jennifer, et al.
(författare)
-
Lessons from the pandemic : Responding to emerging zoonotic viral diseases-a Keystone Symposia report
- 2022
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1518:1, s. 209-225
-
Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
|
|
| 4. |
- Böhm, Johann, et al.
(författare)
-
Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
-
Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
-
Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
|
|
| 5. |
- Dowling, Thomas, et al.
(författare)
-
Rapid subglacial streamlined bedform formation at a calving bay margin
- 2016
-
Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 31:8, s. 879-892
-
Tidskriftsartikel (refereegranskat)abstract
- Using the LiDAR-derived Swedish national height model we have identified previously undescribed shallow streamlined glacial bedforms, small-scale drumlins, on the Närke plain in south-central Sweden. These drumlins could only be detected with high-resolution LiDAR, due to both their subtle size and forest cover. In this area the ice margin receded in a subaqueous environment with a proglacial water depth in the order of 100 m during the last deglaciation. As indicated by the configuration of marginally formed De Geer moraine ridges draping the drumlinoids, the receding ice margin formed deeply indented calving bays. These were located around subaqueous outlets of the subglacial melt-water drainage, with their apex position marked geomorphologically by beaded esker ridges. The mapped small-scale drumlins are aligned perpendicular to the reconstructed ice sheet margin and suggest formation along flow lines adjusted to the configuration of these calving embayments as they propagated up-flow with ice margin retreat. Based on these geometric relationships we argue that the emplacement of the drumlins was near-marginal, ∼7.7–1 km from the margin, on a short timescale (∼5–35 years).
|
|
| 6. |
- Hagos, Desta Haileselassie, et al.
(författare)
-
ExtremeEarth Meets Satellite Data From Space
- 2021
-
Ingår i: IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1939-1404 .- 2151-1535. ; 14, s. 9038-9063
-
Tidskriftsartikel (refereegranskat)abstract
- Bringing together a number of cutting-edge technologies that range from storing extremely large volumes of data all the way to developing scalable machine learning and deep learning algorithms in a distributed manner and having them operate over the same infrastructure poses unprecedented challenges. One of these challenges is the integration of European Space Agency (ESA)'s Thematic Exploitation Platforms (TEPs) and data information access service platforms with a data platform, namely Hopsworks, which enables scalable data processing, machine learning, and deep learning on Copernicus data, and development of very large training datasets for deep learning architectures targeting the classification of Sentinel images. In this article, we present the software architecture of ExtremeEarth that aims at the development of scalable deep learning and geospatial analytics techniques for processing and analyzing petabytes of Copernicus data. The ExtremeEarth software infrastructure seamlessly integrates existing and novel software platforms and tools for storing, accessing, processing, analyzing, and visualizing large amounts of Copernicus data. New techniques in the areas of remote sensing and artificial intelligence with an emphasis on deep learning are developed. These techniques and corresponding software presented in this article are to be integrated with and used in two ESA TEPs, namely Polar and Food Security TEPs. Furthermore, we present the integration of Hopsworks with the Polar and Food Security use cases and the flow of events for the products offered through the TEPs.
|
|
| 7. |
- Jung, Christian, et al.
(författare)
-
A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
-
Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
-
Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
|
|
| 8. |
- Lloyd, B., et al.
(författare)
-
Overview of physics results from MAST
- 2007
-
Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 47:10, s. S658-S667
-
Tidskriftsartikel (refereegranskat)abstract
- Substantial advances have been made on the Mega AmpÚre Spherical Tokamak (MAST). The parameter range of the MAST confinement database has been extended and it now also includes pellet-fuelled discharges. Good pellet retention has been observed in H-mode discharges without triggering an ELM or an H/L transition during peripheral ablation of low speed pellets. Co-ordinated studies on MAST and DIII-D demonstrate a strong link between the aspect ratio and the beta scaling of H-mode energy confinement, consistent with that obtained when MAST data were merged with a subset of the ITPA database. Electron and ion ITBs are readily formed and their evolution has been investigated. Electron and ion thermal diffusivities have been reduced to values close to the ion neoclassical level. Error field correction coils have been used to determine the locked mode threshold scaling which is comparable to that in conventional aspect ratio tokamaks. The impact of plasma rotation on sawteeth has been investigated and the results have been well-modelled using the MISHKA-F code. Alfvén cascades have been observed in discharges with reversed magnetic shear. Measurements during off-axis NBCD and heating are consistent with classical fast ion modelling and indicate efficient heating and significant driven current. Central electron Bernstein wave heating has been observed via the O-X-B mode conversion process in special magnetically compressed plasmas. Plasmas with low pedestal collisionality have been established and further insight has been gained into the characteristics of filamentary structures at the plasma edge. Complex behaviour of the divertor power loading during plasma disruptions has been revealed by high resolution infra-red measurements.
|
|
| 9. |
- Meyer, H., et al.
(författare)
-
Overview of physics results from MAST
- 2009
-
Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 49:10, s. 104017-
-
Tidskriftsartikel (refereegranskat)abstract
- Several improvements to the MAST plant and diagnostics have facilitated new studies advancing the physics basis for ITER and DEMO, as well as for future spherical tokamaks (STs). Using the increased heating capabilities P-NBI <= 3.8 MW H-mode at I-P = 1.2 MA was accessed showing that the energy confinement on MAST scales more weakly with I-P and more strongly with B-t than in the ITER IPB98(y, 2) scaling. Measurements of the fuel retention of shallow pellets extrapolate to an ITER particle throughput of 70% of its original designed total throughput capacity. The anomalous momentum diffusion, chi(phi), is linked to the ion diffusion, chi(i), with a Prandtl number close to P-phi approximate to chi(phi)/chi(i) approximate to 1, although chi(i) approaches neoclassical values. New high spatial resolution measurements of the edge radial electric field, E-r, show that the position of steepest gradients in electron pressure and E-r (i.e. shearing rate) are coincident, but their magnitudes are not linked. The T-e pedestal width on MAST scales with root beta(ped)(pol) rather than rho(pol). The edge localized mode (ELM) frequency for type-IV ELMs, new in MAST, was almost doubled using n = 2 resonant magnetic perturbations from a set of four external coils (n = 1, 2). A new internal 12 coil set (n <= 3) has been commissioned. The filaments in the inter-ELM and L-mode phase are different from ELM filaments, and the characteristics in L-mode agree well with turbulence calculations. A variety of fast particle driven instabilities were studied from 10 kHz saturated fishbone like activity up to 3.8 MHz compressional Alfven eigenmodes. Fast particle instabilities also affect the off-axis NBI current drive, leading to fast ion diffusion of the order of 0.5 m(2) s(-1) and a reduction in the driven current fraction from 40% to 30%. EBW current drive start-up is demonstrated for the first time in a ST generating plasma currents up to 55 kA. Many of these studies contributed to the physics basis of a planned upgrade to MAST.
|
|
| 10. |
- Möller, Per, et al.
(författare)
-
Equifinality in glacial geomorphology: instability theory examined via ribbed moraine and drumlins in Sweden
- 2018
-
Ingår i: GFF. - : Informa UK Limited. - 2000-0863 .- 1103-5897. ; 140:2, s. 106-135
-
Tidskriftsartikel (refereegranskat)abstract
- A contemporary trend in glacial geomorphology is the quest for a unifying theory of drumlin and ribbed moraine formation. Three Swedish example areas of each are here newly mapped, using high-resolution Light Detecting and Ranging (LiDAR) data. From previous ribbed moraine studies in these areas, we know that they formed differently, one by melt-out of stagnant debris-zonated ice, another by remoulding of pre-existing landforms and the third by active subglacial stacking and folding of sediment into proto ridges, contemporaneously with lee-side cavity sediment infill. Through previous work on streamlined terrain in Sweden we know that rock-cored drumlins dominate, while soft-cored drumlins are much less common. The morphology of both types varies along a continuum, whereas their processes of formation differ. Our field examples from ribbed moraine tracts and streamlined terrain suggest that the subglacial environment contains a suite of different ice-sediment physics that, irrespective of this, leads to an equifinality of shape of some subglacial landforms (ribbed moraine and streamlined terrain) despite the differences in the detail of their process of formation. We thus argue that different processes, on their own or in combination, lead to a similar form of morphometric expression, that is, equifinality, and the quest for a unifying process of formation is a misleading one. Furthermore, we argue that large morphological data sets of subglacial landforms can only be used to classify features as part of a formation continuum – or not – when they are used in conjunction with the sedimentology of said landforms.
|
|
