| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Insausti, Ricardo, et al.
(författare)
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Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies
- 2023
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Ingår i: Frontiers in Neuroanatomy. - : Frontiers Media SA. - 1662-5129. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor’s body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
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| 3. |
- Álvarez-Buylla, Elena R., et al.
(författare)
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B-Function Expression in the Flower Center Underlies the Homeotic Phenotype of Lacandonia schismatica (Triuridaceae)
- 2010
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Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 22:11, s. 3543-3559
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Tidskriftsartikel (refereegranskat)abstract
- Spontaneous homeotic transformations have been described in natural populations of both plants and animals, but little is known about the molecular-genetic mechanisms underlying these processes in plants. In the ABC model of floral organ identity in Arabidopsis thaliana, the B- and C-functions are necessary for stamen morphogenesis, and C alone is required for carpel identity. We provide ABC model-based molecular-genetic evidence that explains the unique inside-out homeotic floral organ arrangement of the monocotyledonous mycoheterotroph species Lacandonia schismatica (Triuridaceae) from Mexico. Whereas a quarter million flowering plant species bear central carpels surrounded by stamens, L. schismatica stamens occur in the center of the flower and are surrounded by carpels. The simplest explanation for this is that the B-function is displaced toward the flower center. Our analyses of the spatio-temporal pattern of B- and C-function gene expression are consistent with this hypothesis. The hypothesis is further supported by conservation between the B-function genes of L. schismatica and Arabidopsis, as the former are able to rescue stamens in Arabidopsis transgenic complementation lines, and Ls-AP3 and Ls-PI are able to interact with each other and with the corresponding Arabidopsis B-function proteins in yeast. Thus, relatively simple molecular modifications may underlie important morphological shifts in natural populations of extant plant taxa.
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| 4. |
- Arroyo, F., et al.
(författare)
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Sustainable Na2CO3 production from NaCl waste and CO2 sources using membrane technology
- 2023
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Ingår i: Circular Economy Processes for CO2 Capture and Utilization: Strategies and Case Studies. - 9780323956680 ; , s. 325-346
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter presents the preliminary results related to obtaining Na2CO3 through membrane distillation in a carbon capture and utilization scheme for the circular economy. This process is developed in a circular economy framework in which value can be given to waste streams or brines with high NaCl contents. The process proposes to capture CO2 from streams from multiple industrial processes such as biogas, combustion streams, or typical standard flue gases, based on a membrane process. The permeate and salt fluxes obtained when using membrane distillation to concentrate Na2CO3 have been explored. This was carried out through an experimental design which served to obtain a reliable model to predict permeate flux according to feed rate and feed temperature. The results showed that, for the range tested, the influence of the feed rate is greater than the influence of the temperature.
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| 5. |
- Artiglia, Luca, et al.
(författare)
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A surface-stabilized ozonide triggers bromide oxidation at the aqueous solution-vapour interface
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of bromide in aqueous environments initiates the formation of molecular halogen compounds, which is important for the global tropospheric ozone budget. In the aqueous bulk, oxidation of bromide by ozone involves a [Br center dot OOO-] complex as intermediate. Here we report liquid jet X-ray photoelectron spectroscopy measurements that provide direct experimental evidence for the ozonide and establish its propensity for the solution-vapour interface. Theoretical calculations support these findings, showing that water stabilizes the ozonide and lowers the energy of the transition state at neutral pH. Kinetic experiments confirm the dominance of the heterogeneous oxidation route established by this precursor at low, atmospherically relevant ozone concentrations. Taken together, our results provide a strong case of different reaction kinetics and mechanisms of reactions occurring at the aqueous phase-vapour interface compared with the bulk aqueous phase.
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| 6. |
- Cooper, Declan L.M., et al.
(författare)
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Consistent patterns of common species across tropical tree communities
- 2024
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 728-734
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Tidskriftsartikel (refereegranskat)abstract
- Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1–6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.
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| 7. |
- González-Castaño, Miriam, et al.
(författare)
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3D-printed structured catalysts for CO 2 methanation reaction: Advancing of gyroid-based geometries
- 2022
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Ingår i: Energy Conversion and Management. - : Elsevier BV. - 0196-8904. ; 258
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Forskningsöversikt (refereegranskat)abstract
- This work investigates the CO2 methanation rate of structured catalysts by tuning the geometry of 3D-printed metal Fluid Guiding Elements (FGEs) structures based on periodically variable pseudo-gyroid geometries. The enhanced performance showed by the structured catalytic systems is mostly associated with the capability of the FGEs substrate geometries for efficient heat usages. Thus, variations on the channels diameter resulted in ca. 25% greater CO2 conversions values at intermediate temperature ranges. The highest void fraction evidenced in the best performing catalyst (3D-1) favored the radial heat transfer and resulted in significantly enhanced catalytic activity, achieving close to equilibrium (75%) conversions at 400 °C and 120 mL/min. For the 3D-1 catalyst, a mathematical model based on an experimental design was developed thus enabling the estimation of its behavior as a function of temperature, spatial velocity, hydrogen to carbon dioxide (H2/CO2) ratio, and inlet CO2 concentration. Its optimal operating conditions were established under 3 different scenarios: 1) no restrictions, 2) minimum H2:CO2 ratios, and 3) minimum temperatures and H2/CO2 ratio. For instance, for the lattest scenario, the best CO2 methanation conditions require operating at 431 °C, 200 mL/min, H2/CO2 = 3 M ratio, and inlet CO2 concentration = 10 %.
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| 8. |
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| 9. |
- Householder, John Ethan, et al.
(författare)
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One sixth of Amazonian tree diversity is dependent on river floodplains
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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| 10. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 11. |
- Luize, Bruno Garcia, et al.
(författare)
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Geography and ecology shape the phylogenetic composition of Amazonian tree communities
- 2024
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Ingår i: JOURNAL OF BIOGEOGRAPHY. - 0305-0270 .- 1365-2699.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Amazonia hosts more tree species from numerous evolutionary lineages, both young and ancient, than any other biogeographic region. Previous studies have shown that tree lineages colonized multiple edaphic environments and dispersed widely across Amazonia, leading to a hypothesis, which we test, that lineages should not be strongly associated with either geographic regions or edaphic forest types. Location: Amazonia. Taxon: Angiosperms (Magnoliids; Monocots; Eudicots). Methods: Data for the abundance of 5082 tree species in 1989 plots were combined with a mega-phylogeny. We applied evolutionary ordination to assess how phylogenetic composition varies across Amazonia. We used variation partitioning and Moran's eigenvector maps (MEM) to test and quantify the separate and joint contributions of spatial and environmental variables to explain the phylogenetic composition of plots. We tested the indicator value of lineages for geographic regions and edaphic forest types and mapped associations onto the phylogeny. Results: In the terra firme and v & aacute;rzea forest types, the phylogenetic composition varies by geographic region, but the igap & oacute; and white-sand forest types retain a unique evolutionary signature regardless of region. Overall, we find that soil chemistry, climate and topography explain 24% of the variation in phylogenetic composition, with 79% of that variation being spatially structured (R-2 = 19% overall for combined spatial/environmental effects). The phylogenetic composition also shows substantial spatial patterns not related to the environmental variables we quantified (R-2 = 28%). A greater number of lineages were significant indicators of geographic regions than forest types. Main Conclusion: Numerous tree lineages, including some ancient ones (>66 Ma), show strong associations with geographic regions and edaphic forest types of Amazonia. This shows that specialization in specific edaphic environments has played a long-standing role in the evolutionary assembly of Amazonian forests. Furthermore, many lineages, even those that have dispersed across Amazonia, dominate within a specific region, likely because of phylogenetically conserved niches for environmental conditions that are prevalent within regions.
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| 12. |
- Ravikumar, Sadhana, et al.
(författare)
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Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology
- 2021
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.
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| 13. |
- Ravikumar, Sadhana, et al.
(författare)
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Improved Segmentation of Deep Sulci in Cortical Gray Matter Using a Deep Learning Framework Incorporating Laplace’s Equation
- 2023
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Ingår i: Information Processing in Medical Imaging - 28th International Conference, IPMI 2023, Proceedings. - 1611-3349 .- 0302-9743. - 9783031340475 ; 13939 LNCS, s. 692-704
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Konferensbidrag (refereegranskat)abstract
- When developing tools for automated cortical segmentation, the ability to produce topologically correct segmentations is important in order to compute geometrically valid morphometry measures. In practice, accurate cortical segmentation is challenged by image artifacts and the highly convoluted anatomy of the cortex itself. To address this, we propose a novel deep learning-based cortical segmentation method in which prior knowledge about the geometry of the cortex is incorporated into the network during the training process. We design a loss function which uses the theory of Laplace’s equation applied to the cortex to locally penalize unresolved boundaries between tightly folded sulci. Using an ex vivo MRI dataset of human medial temporal lobe specimens, we demonstrate that our approach outperforms baseline segmentation networks, both quantitatively and qualitatively.
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| 14. |
- Ravikumar, Sadhana, et al.
(författare)
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Unfolding the Medial Temporal Lobe Cortex to Characterize Neurodegeneration Due to Alzheimer’s Disease Pathology Using Ex vivo Imaging
- 2021
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Ingår i: Machine Learning in Clinical Neuroimaging - 4th International Workshop, MLCN 2021, Held in Conjunction with MICCAI 2021, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030875855 ; 13001 LNCS, s. 3-12
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Konferensbidrag (refereegranskat)abstract
- Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology.
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| 15. |
- Roh, Hyung S., et al.
(författare)
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Integrating Color Deconvolution Thresholding and Weakly Supervised Learning for Automated Segmentation of Neurofibrillary Tangle and Neuropil Threads
- 2023
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Ingår i: Medical Imaging 2023 : Digital and Computational Pathology - Digital and Computational Pathology. - 1605-7422. - 9781510660472 ; 12471
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Konferensbidrag (refereegranskat)abstract
- Abnormally phosphorylated tau proteins are known to be a major indicator of Alzheimer's Disease (AD) with strong association with memory loss and cognitive decline. Automated generation of pixel-wise accurate neurofibrillary tangles (NFTs) and neuropil threads (NTs) segmentation is a challenging task, due to lack of ground truth segmentation data of these abnormal tau pathology. This problem is most prominent in the case of segmenting NTs, where the small threadlike morphology makes pixel-wise labeling a laborious task and unrealistic for large-scale studies. Lack of ground truth data poses a significant limitation for many learning-based methods to generate accurate segmentations of NFTs and NTs. This work presents an automated pipeline for pixel level segmentation of NFTs and NTs that does not rely on ground truth segmentation data. The pipeline is composed of four main steps: (1) color deconvolution is used to separate histopathology images into staining channels (DAB, Hematoxylin, and Eosin), (2) Otsu's thresholding is used on the DAB stain channel to generate pixel level segmentation of abnormal tau proteins staining, (3) a weakly-supervised learning paradigm (WildCat), using only global descriptors of images, is used to generate density maps of potential regions of NFTs and NTs, and (4) density maps and segmentations are then integrated using connected component analysis to localize NFTs and NTs in the detected tau segmentations. Our results show high global classification accuracy for NFTs (Acc:0.96) and NTs (Acc:0.91), and statistically significant distinctions when evaluating the percent area occupied of the detected NTs relative to expert ratings of NTs severity. Qualitative assessment of the NFTs and NTs results showed accurate pixel-level segmentations of the NFTs, while modest performance for NTs.
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| 16. |
- ter Steege, Hans, et al.
(författare)
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Mapping density, diversity and species-richness of the Amazon tree flora
- 2023
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Ingår i: COMMUNICATIONS BIOLOGY. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution. A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.
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| 17. |
- Yushkevich, Paul A., et al.
(författare)
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Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe
- 2021
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:9, s. 2784-2797
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Tidskriftsartikel (refereegranskat)abstract
- Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.
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| 18. |
- Zapatero-Belinchón, Francisco J., et al.
(författare)
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Interdependent Impact of Lipoprotein Receptors and Lipid-Lowering Drugs on HCV Infectivity
- 2021
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- The HCV replication cycle is tightly associated with host lipid metabolism: Lipoprotein receptors SR-B1 and LDLr promote entry of HCV, replication is associated with the formation of lipid-rich membranous organelles and infectious particle assembly highjacks the very‑low-density lipoprotein (VLDL) secretory pathway. Hence, medications that interfere with the lipid metabolism of the cell, such as statins, may affect HCV infection. Here, we study the interplay between lipoprotein receptors, lipid homeostasis, and HCV infection by genetic and pharmacological interventions. We found that individual ablation of the lipoprotein receptors SR‑B1 and LDLr did not drastically affect HCV entry, replication, or infection, but double lipoprotein receptor knock-outs significantly reduced HCV infection. Furthermore, we could show that this effect was neither due to altered expression of additional HCV entry factors nor caused by changes in cellular cholesterol content. Strikingly, whereas lipid‑lowering drugs such as simvastatin or fenofibrate did not affect HCV entry or infection of immortalized hepatoma cells expressing SR-B1 and/or LDLr or primary human hepatocytes, ablation of these receptors rendered cells more susceptible to these drugs. Finally, we observed no significant differences between statin users and control groups with regards to HCV viral load in a cohort of HCV infected patients before and during HCV antiviral treatment. Interestingly, statin treatment, which blocks the mevalonate pathway leading to decreased cholesterol levels, was associated with mild but appreciable lower levels of liver damage markers before HCV therapy. Overall, our findings confirm the role of lipid homeostasis in HCV infection and highlight the importance of the mevalonate pathway in the HCV replication cycle.
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| 19. |
- Zola, Enria, et al.
(författare)
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Expected Bit Rate for Terminals Moving According to the Random Waypoint Model in a WLAN Cell
- 2013
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Konferensbidrag (refereegranskat)abstract
- The IEEE 802.11 standard defines the different bit rates and modulation schemes to which a WLAN device may adapt according to the channel quality. User mobility may also have an impact on the available bit rate. This paper presents a study of the bit rate evolution along time for devices that move according to the Random Waypoint mobility pattern in WLAN cells. Simulation has been applied in order to obtain statistical results that permit to characterize the evolution of the bit rate behavior along time and to compute average results in the ideal case (without interference) and in the presence of interfering devices. Our results can be useful in the solution of optimization problems in which decision on where to connect must be taken based on some minimum guaranteed bit rate. They also can be useful in the design of inter and intra-cell handover methods and load balancing schemes.
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| 20. |
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