| 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. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 4. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Bosch Campos, Ana, et al.
(författare)
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PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer
- 2015
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 7:283, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Activating mutations of PIK3CA are the most frequent genomic alterations in estrogen receptor (ER)-positive breast tumors, and selective phosphatidylinositol 3-kinase a (PI3Kα) inhibitors are in clinical development. The activity of these agents, however, is not homogeneous, and only a fraction of patients bearing PIK3CA-mutant ER-positive tumors benefit from single-agent administration. Searching for mechanisms of resistance, we observed that suppression of PI3K signaling results in induction of ER-dependent transcriptional activity, as demonstrated by changes in expression of genes containing ER-binding sites and increased occupancy by the ER of promoter regions of upregulated genes. Furthermore, expression of ESR1 mRNA and ER protein were also increased upon PI3K inhibition. These changes in gene expression were confirmed in vivo in xenografts and patient-derived models and in tumors from patients undergoing treatment with the PI3Kα inhibitor BYL719. The observed effects on transcription were enhanced by the addition of estradiol and suppressed by the anti-ER therapies fulvestrant and tamoxifen. Fulvestrant markedly sensitized ER-positive tumors to PI3Kα inhibition, resulting in major tumor regressions in vivo. We propose that increased ER transcriptional activity may be a reactive mechanism that limits the activity of PI3K inhibitors and that combined PI3K and ER inhibition is a rational approach to target these tumors.
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| 6. |
- Gudbjartsson, Daniel F., et al.
(författare)
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Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:3, s. 342-347
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).
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| 7. |
- Gutierrez, Jesus, et al.
(författare)
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Subjective evaluation of visual quality and simulator sickness of short 360 videos : ITU-T Rec. P.919
- 2022
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Ingår i: IEEE transactions on multimedia. - 1520-9210 .- 1941-0077. ; 24, s. 3087-3100
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Tidskriftsartikel (refereegranskat)abstract
- Recently an impressive development in immersive technologies, such as Augmented Reality (AR), Virtual Reality (VR) and 360 video, has been witnessed. However, methods for quality assessment have not been keeping up. This paper studies quality assessment of 360 video from the cross-lab tests (involving ten laboratories and more than 300 participants) carried out by the Immersive Media Group (IMG) of the Video Quality Experts Group (VQEG). These tests were addressed to assess and validate subjective evaluation methodologies for 360 video. Audiovisual quality, simulator sickness symptoms, and exploration behavior were evaluated with short (from 10 seconds to 30 seconds) 360 sequences. The following factors' influences were also analyzed: assessment methodology, sequence duration, Head-Mounted Display (HMD) device, uniform and non-uniform coding degradations, and simulator sickness assessment methods. The obtained results have demonstrated the validity of Absolute Category Rating (ACR) and Degradation Category Rating (DCR) for subjective tests with 360 videos, the possibility of using 10-second videos (with or without audio) when addressing quality evaluation of coding artifacts, as well as any commercial HMD (satisfying minimum requirements). Also, more efficient methods than the long Simulator Sickness Questionnaire (SSQ) have been proposed to evaluate related symptoms with 360 videos. These results have been instrumental for the development of the ITU-T Recommendation P.919. Finally, the annotated dataset from the tests is made publicly available for the research community.
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| 8. |
- Gutierrez, Jesus, et al.
(författare)
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Subjective evaluation of visual quality and simulator sickness of short 360 videos : ITU-T Rec. P.919
- 2022
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Ingår i: IEEE transactions on multimedia. - : Institute of Electrical and Electronics Engineers (IEEE). - 1520-9210 .- 1941-0077. ; 24, s. 3087-3100
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Tidskriftsartikel (refereegranskat)abstract
- Recently an impressive development in immersive technologies, such as Augmented Reality (AR), Virtual Reality (VR) and 360 video, has been witnessed. However, methods for quality assessment have not been keeping up. This paper studies quality assessment of 360 video from the cross-lab tests (involving ten laboratories and more than 300 participants) carried out by the Immersive Media Group (IMG) of the Video Quality Experts Group (VQEG). These tests were addressed to assess and validate subjective evaluation methodologies for 360 video. Audiovisual quality, simulator sickness symptoms, and exploration behavior were evaluated with short (from 10 seconds to 30 seconds) 360 sequences. The following factors' influences were also analyzed: assessment methodology, sequence duration, Head-Mounted Display (HMD) device, uniform and non-uniform coding degradations, and simulator sickness assessment methods. The obtained results have demonstrated the validity of Absolute Category Rating (ACR) and Degradation Category Rating (DCR) for subjective tests with 360 videos, the possibility of using 10-second videos (with or without audio) when addressing quality evaluation of coding artifacts, as well as any commercial HMD (satisfying minimum requirements). Also, more efficient methods than the long Simulator Sickness Questionnaire (SSQ) have been proposed to evaluate related symptoms with 360 videos. These results have been instrumental for the development of the ITU-T Recommendation P.919. Finally, the annotated dataset from the tests is made publicly available for the research communit
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| 9. |
- John, Viola, et al.
(författare)
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Comperative ecological Life Cycle Assessment for residential buildings
- 2011
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Ingår i: World Sustainable Building Conference 2011, October 18-21, 2011, Helsinki, Finland.
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Konferensbidrag (refereegranskat)abstract
- Life Cycle Assessment (LCA) offers a viable way of evaluating a buildings environmental impact throughout all life phases (construction, use/occupation and deconstruction). However, LCAs of buildings still need to be well-established so that in the future, architects and planners will already be able to conduct them at early design stages. The evaluation of residential buildings, which for instance in Switzerland contribute about 88% to the overall Swiss building stock [1], will be especially important in the future in order to minimize environmental impacts. The Chair of Sustainable Construction at ETH Zurich is conducting a major research study on how to assure comparability, reliability and simplification of LCAs on residential buildings in the future. In a representative study, up to 100 residential apartment buildings are analyzed. The aim of this study is to integrate complexity in LCA by means of identifying those building parameters (e.g. construction materials and components, heating energy, etc.) most relevant for LCAs in typical apartment buildings in terms of their environmental impacts, while also considering economic aspects. In this instance, only Swiss buildings are examined, however, the methodology is generally applicable. Based on this analysis, a concept for a light standardized LCA tool for Swiss residential apartment buildings will be developed which enables architects and planners to easily evaluate the environmental impacts of a building right from the beginning of the design process. This paper introduces the methodological approach applied in the ETH research project Life Cycle Assessment of Infrastructure - Buildings.
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| 10. |
- John, Viola, et al.
(författare)
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Hoch oder quer? Ökologische Lebenszyklusanalyse eines Hochhauses im Vergleich zu einem Riegelgebäude
- 2010
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Ingår i: Bauingenieur. - 0005-6650. ; :8, s. 341-352
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Tidskriftsartikel (refereegranskat)abstract
- Urban sprawl is a worldwide tendency leading to an increased demand for adequate highly condensed living space within cities. To meet this demand, there are two typical building types: the high rise and the elongate apartment building. This article aims at providing a comparative ecological life cycle assessment (LCA) for the structure of these two building types. For the analysis, an existing elongate apartment building, planned for a site with bad soil conditions and a high groundwater level in Zurich, was examined. This building was then compared to a hypothetic high rise building, designed for the same site in Zurich and meeting identical energy standards as well as containing a comparable amount of accommodation units and floor space. The weighting of the environmental impact of the buildings over their entire lifecycle was illustrated through two different weighting indices (Eco-Indicator 99 [1], Ecological Scarcity ’06 [2]). Additionally, the cumulative energy demand (CED) [3] for both buildings was calculated. Afterwards, a sensitivity analysis was conducted, accounting for the influence of improved soil properties and a low groundwater level. The LCA results show that with bad soil properties, the high rise building has a significantly lower cumulative energy demand and environmental impact than the elongate building, whereas improved soil properties lead to the elongate building exceeding the high rise building in terms of environmental impacts.
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