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- 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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3. |
- Kim, Joon Tae, et al.
(författare)
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Dual antiplatelet Use for extended period taRgeted to AcuTe ischemic stroke with presumed atherosclerotic OrigiN (DURATION) trial : Rationale and design
- 2023
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 18:8, s. 1015-1020
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407.
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4. |
- DeCarolis, Joseph, et al.
(författare)
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Leveraging Open-Source Tools for Collaborative Macro-energy System Modeling Efforts
- 2020
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Ingår i: Joule. - : Elsevier BV. - 2542-4351. ; 4:12, s. 2523-2526
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The authors are founding team members of a new effort to develop an Open Energy Outlook for the United States. The effort aims to apply best practices of policy-focused energy system modeling, ensure transparency, build a networked community, and work toward a common purpose: examining possible US energy system futures to inform energy and climate policy efforts. Individual author biographies can be found on the project website: https://openenergyoutlook.org/. DeCarolis et al. articulate the benefits of forming collaborative teams with a wide array of disciplinary and domain expertise to conduct analysis with macro-energy system models. Open-source models, tools, and datasets underpin such efforts by enabling transparency, accessibility, and replicability among team members and with the broader modeling community.
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5. |
- Földváry Ličina, Veronika, et al.
(författare)
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Development of the ASHRAE Global Thermal Comfort Database II
- 2018
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Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323. ; 142, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- Recognizing the value of open-source research databases in advancing the art and science of HVAC, in 2014 the ASHRAE Global Thermal Comfort Database II project was launched under the leadership of University of California at Berkeley's Center for the Built Environment and The University of Sydney's Indoor Environmental Quality (IEQ) Laboratory. The exercise began with a systematic collection and harmonization of raw data from the last two decades of thermal comfort field studies around the world. The ASHRAE Global Thermal Comfort Database II (Comfort Database), now an online, open-source database, includes approximately 81,846 complete sets of objective indoor climatic observations with accompanying “right-here-right-now” subjective evaluations by the building occupants who were exposed to them. The database is intended to support diverse inquiries about thermal comfort in field settings. A simple web-based interface to the database enables filtering on multiple criteria, including building typology, occupancy type, subjects' demographic variables, subjective thermal comfort states, indoor thermal environmental criteria, calculated comfort indices, environmental control criteria and outdoor meteorological information. Furthermore, a web-based interactive thermal comfort visualization tool has been developed that allows end-users to quickly and interactively explore the data.
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6. |
- Hellwig, Runa T., et al.
(författare)
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A framework for adopting adaptive thermal comfort principles in design and operation of buildings
- 2019
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Ingår i: Energy and Buildings. - : Elsevier BV. - 0378-7788. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- The concept of adaptive thermal comfort was formulated many decades ago and has been validated in numerous field studies. As a result, wider acceptable indoor temperature ranges based on adaptive models have been included in international and national standards and the adaptive approach to thermal comfort is regarded as a significant contributor in achieving low energy building design and operation. Despite the ever-increasing scientific literature on adaptive comfort around the world, the overall understanding of how to translate the adaptive principles into design practice and concepts for operating buildings is still limited, which suggests a gap between the scientific outcomes and the real-world applications. This discussion paper identifies the challenges and gaps in using the principles of adaptive thermal comfort by design practitioners and discusses them in light of relevant research findings. More than 100 literature sources were reviewed in support of the discussion. The paper then proposes a framework that aims to facilitate the adoption of adaptive comfort principles in design and operation of buildings and describes the outline of an imminent guideline for low energy building design based on the concept of adaptive thermal comfort.
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7. |
- Hellwig, Runa T., et al.
(författare)
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Applying adaptive principles: Developing guidance for planning practice
- 2019
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Ingår i: PROCEEDINGS OF THE 1ST INTERNATIONAL CONFERENCE ON COMFORT AT THE EXTREMES: ENERGY, ECONOMY AND CLIMATE.
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Konferensbidrag (refereegranskat)abstract
- One of the major challenges of building industry today is to provide indoor spaces allowing the occupants to make themselves comfortable while achieving low energy consumption. Considering the observed increasing temperatures and a more extreme climate, this becomes even more urgent and difficult to accomplish. It is therefore necessary to rely on approaches than contribute to sustainable building design, such as the adaptive approach to thermal comfort which postulates that people are not passive recipients of their environment but adapt behaviourally, physiologically and psychologically. The concept of adaptive thermal comfort was formulated many decades ago and has been validated in numerous field studies. Temperature thresholds based on adaptive models have been included in international and national standards. However, the overall understanding of how to translate the adaptive principles into design practice and concepts for operating buildings is still limited. Subtask B of IEA Annex 69 addresses this gap: “Strategy and practice of adaptive thermal comfort in low energy buildings”. The subtask aims to develop guidelines for low energy buildings that include the principle of adaptive comfort. This paper discusses the challenges and gaps identified in using the principles of adaptive thermal comfort in building design and operation and outlines the contents of the imminent guideline.
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8. |
- Hellwig, Runa T., et al.
(författare)
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Design of adaptive opportunities for people in buildings
- 2022
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Ingår i: Routledge Handbook of Resilient Thermal Comfort. - London : Routledge. - 9781003244929 ; , s. 193-209
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Adaptive opportunities for people are a key element in the adaptive thermal comfort approach. Research has led to a broad and solid foundation of knowledge, but design processes on how to support people’s behavioural control through building design are still missing. This chapter presents a design process for incorporating adaptive opportunities and discusses how such an approach enhances thermal resilience. The design process is facilitated with tools and exemplary design or operation actions for stakeholders. Non-energy using adaptive opportunities and the passive performance a building affords are the means to enhance not only human thermal comfort in buildings but also human resilience. This is because they offer people concrete options for acting and supporting their belief in their ability and skills to act in case of extreme weather events and can hence facilitate physiological adaptation. They are therefore paramount to build a resilient human-building interaction in a changing environment.
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9. |
- Hellwig, Runa T., et al.
(författare)
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Guidelines to bridge the gap between adaptive thermal comfort theory and building design and operation practice
- 2020
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Ingår i: 11th Windsor Conference: Resilient Comfort, WINDSOR 2020 - Proceedings. ; , s. 529-545
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Konferensbidrag (refereegranskat)abstract
- Adaptive thermal comfort guidelines have been developed within the work of Annex 69: “Strategy and practice of adaptive thermal comfort in low energy buildings”. The guidelines have been established based on a framework for adopting adaptive thermal comfort principles in building design and operation developed by the authors. The guidelines target building practitioners, addressing the critical interrelated role building planners, building operators and occupants play. A successful adaptive thermal comfort design, in which design for human thermal adaptation is foreseen, planned, and carefully embedded in the design and operation intent, is based on broad knowledge and understanding of the multiple quantifiable and non-quantifiable factors influencing human perception, as well as human building interaction. Adaptive building design follows a user-centric integrated design approach and therefore it is critical to consider the occupants' and the operators' role in buildings already in the design phase. This paper focuses on three main challenges identified earlier and how these are addressed in the guidelines, i.e. i) updating prevailing knowledge about human thermophysiology and adaptation, ii) developing a procedure for design of adaptive opportunities, and iii) providing guidance for operational planning and operation of adaptive buildings. The challenge for future research remains to assess the magnitude of how specific design decisions affect particular adaptive mechanisms.
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10. |
- Kwon, Hyuk Sung, et al.
(författare)
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Early increment of soluble triggering receptor expressed on myeloid cells 2 in plasma might be a predictor of poor outcome after ischemic stroke
- 2020
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Ingår i: Journal of clinical neuroscience. - : ELSEVIER SCI LTD. - 0967-5868 .- 1532-2653. ; 73, s. 215-218
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Tidskriftsartikel (refereegranskat)abstract
- Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) is derived from cleavage of TREM2, which is expressed on the cell surface of microlgia and other tissue-specific macrophages. In the present study, the changes in the sTREM2 levels after ischemic stroke (IS) and their association with clinical outcomes were evaluated. A total of 43 patients diagnosed with non-cardioembolic IS between June 2011 and May 2014 were consecutively included in this study. Patients treated with intravenous thrombolysis or intra-arterial thrombectomy were excluded. Plasma samples were collected three times (days 1, 7, and 90) after ictus. The sTREM2 level was measured in the samples using the highly sensitive solid-phase proximity ligation assay (SP-PLA). Among the 43 subjects, higher initial NIH stroke scale (NIHSS) score (P = 0.005), early increment of sTREM2 (P < 0.001), and late decrement of sTREM2 (P = 0.002), were more common in patients with poor outcome. Based on multivariate analysis, initial NIHSS score (P = 0.015) and early increment of sTREM2 (P = 0.032) were independently associated with poor outcome. The results from the present study indicate that increment of sTREM2 level at the early phase was a predictor of poor outcome. Serial follow-up of sTREM2 may aid prognosis after stroke.
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