| 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. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Blackman, Corey
(författare)
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Evaluation of a thermally driven heat pump for solar heating and cooling applications
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exploiting solar energy technology for both heating and cooling purposes has the potential of meeting an appreciable portion of the energy demand in buildings throughout the year. By developing an integrated, multi-purpose solar energy system, that can operate all twelve months of the year, a high utilisation factor can be achieved which translates to more economical systems. However, there are still some techno-economic barriers to the general commercialisation and market penetration of such technologies. These are associated with high system and installation costs, significant system complexity, and lack of knowledge of system implementation and expected performance. A sorption heat pump module that can be integrated directly into a solar thermal collector has thus been developed in order to tackle the aforementioned market barriers. This has been designed for the development of cost-effective pre-engineered solar energy system kits that can provide both heating and cooling.This thesis summarises the characterisation studies of the operation of individual sorption modules, sorption module integrated solar collectors and a full solar heating and cooling system employing sorption module integrated collectors. Key performance indicators for the individual sorption modules showed cooling delivery for 6 hours at an average power of 40 W and a temperature lift of 21°C. Upon integration of the sorption modules into a solar collector, measured solar radiation energy to cooling energy conversion efficiencies (solar cooling COP) were between 0.10 and 0.25 with average cooling powers between 90 and 200 W/m2 collector aperture area. Further investigations of the sorption module integrated collectors implementation in a full solar heating and cooling system yielded electrical cooling COP ranging from 1.7 to 12.6 with an average of 10.6 for the test period.Additionally, simulations were performed to determine system energy and cost saving potential for various system sizes over a full year of operation for a 140 m2 single-family dwelling located in Madrid, Spain. Simulations yielded an annual solar fraction of 42% and potential cost savings of €386 per annum for a solar heating and cooling installation employing 20m2 of sorption integrated collectors.
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| 4. |
- Blackman, Corey
(författare)
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Evaluation of Modular Thermally Driven Heat Pump Systems
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The building sector accounts for approximately 40% of primary energy use within the European Union, therefore reductions in the energy use intensity of this sector are critical in decreasing total energy usage. Given that the majority of energy used within the built environment is for space conditioning and domestic hot water preparation, prudence would suggest that decreasing primary energy used for these end purposes would have the biggest overall environmental impact. A significant portion of the energy demands in buildings throughout the year could potentially be met using solar energy technology for both heating and cooling. Additionally, improving the efficiency of current heating and cooling appliances can reduce environmental impacts during the transition from non-renewable to renewable sources of energy. However, in spite of favourable energy saving prospects, major energy efficiency improvements as well as solar heating and cooling technology are still somewhat underutilised. This is typically due to higher initial costs, and lack of knowledge of system implementation and expected performance. The central premise of this thesis is that modular thermally (i.e., sorption) driven heat pumps can be integrated into heating and cooling systems to provide energy cost savings. These sorption modules, by virtue of their design, could be integrated directly into a solar thermal collector. With the resulting sorption integrated collectors, cost-effective pre-engineered solar heating and cooling system kits can be developed. Sorption modules could also be employed to improve the efficiency of natural gas driven boilers. These modules would effectively transform standard condensing boilers into high efficiency gas-driven heat pumps that, similar to electric heat pumps, make use of air or ground-source heat. Based on the studies carried, sorption modules are promising for integration into heating and cooling systems for the built environment generating appreciable energy and cost-savings. Simulations yielded an annual solar fraction of 42% and potential cost savings of €386 per annum for a sorption integrated solar heating and cooling installation versus a state-of-the-art heating and cooling system. Additionally, a sorption integrated gas-fired condensing boiler yielded annual energy savings of up to 14.4% and corresponding annual energy cost savings of up to €196 compared to a standard condensing boiler. A further evaluation method for sorption modules, saw the use of an artificial neural network (ANN) to characterise and predict the performance of the sorption module under various operating conditions. This generic, application agnostic model, could characterise sorption module performance within a ± 8% margin of error. This study thus culminates in the proposal of an overall systematic evaluation method for sorption modules that could be employed for various applications based on the analytical, experimental and simulation methods developed.
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| 5. |
- Blackman, Corey, et al.
(författare)
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Experimental Evaluation and Concept Demonstration of a Novel Modular Gas-Driven Sorption Heat Pump
- 2017
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Konferensbidrag (refereegranskat)abstract
- Gas-driven sorption heat pumps (GDSHPs) exhibit possibilities in the reduction of energy use and environmental impact of heating systems that utilise natural gas. By utilising renewable thermal energy from the environment, that is, air, ground or water sources, significant reduction of primary energy use can be achieved. However, high cost, low coefficient of performance (COP) and large volume per unit thermal power produced have limited the proliferation of GDSHPs. In this work, exploiting the benefits of reversible chemical reactions in sorption systems, with no internal moving parts, noise, vibration and maintenance-free reactor design, two novel modular prototype sorption components were developed and evaluated experimentally. They were designed to operate as part of an intermittent cycle GDSHP to deliver heat directly to a load or to a stratified hot water store. Prototype 1 was an ammonia-salt basic sorption unit while prototype 2 was an ammonia-salt resorption unit both employing proprietary composite sorbent materials. Test results showed that the prototype 2 reactor produced a specific heating capacity of 46 W/litre at a temperature lift of 50°C yielding a COP of 1.38. Prototype 1 demonstrated higher heating capacity of 73 W/litre at a temperature lift of 70°C but exhibited lower COP of 1.10. Given its higher COP but lower temperature lift, prototype 2 could be employed in a GDSHP designed for moderate heating demands or where a ground source heat exchanger is employed as the low temperature heat source. In the case where a higher temperature lift is required, for example, for an air-source GDSHP unit then the prototype 1 design would be more applicable.
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| 6. |
- Blackman, Corey, et al.
(författare)
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Techno-economic evaluation of solar-assisted heating and cooling systems with sorption module integrated solar collectors
- 2015
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 70, s. 409-417, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- Currently the use of solar energy for heating and cooling isn't widespread. In order to reduce primary energy consumption in the built environment along with improving the thermal performance of the current building stock, retrofit solutions are required to utilise renewable energy. Using solar energy to reduce primary energy consumption is seen as a possible solution. With the precipitous fall in the prices of crystalline solar photovoltaic modules, utilising this technology to reduce electrical energy consumption for cooling is an attractive solution. Recently, a sorption module integrated collector has been developed in order to improve cost-effectiveness and simplify solar thermal heating and cooling systems. A techno-economic analysis has been performed to evaluate solar photovoltaic cooling and solar thermal cooling systems for residential renewable energy retrofit. The analysis is based on potential energy and cost savings according to simulated heating and cooling loads under climatic conditions of Madrid, Spain. Simplified models were used to determine heating and cooling demands and the solar energy contribution to heating and cooling loads. Additionally, given the sorption collector's unique capacity to store solar energy thermally and provide cooling at night an analysis has been carried out to identify the combined benefit of solar-assisted heating and cooling via photovoltaics during the day and solar sorption at night. For system sizes between 5m(2) and 20m(2) solar fractions between 16% and 64% could be achieved which translated to annual energy cost savings between (sic)153 to (sic)615. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 7. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 8. |
- Zivanovic, Andrej, et al.
(författare)
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Co-evolution of AR gene copy number and structural complexity in endocrine therapy resistant prostate cancer
- 2023
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Ingår i: NAR Cancer. - : Oxford University Press. - 2632-8674. ; 5:3
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Tidskriftsartikel (refereegranskat)abstract
- Androgen receptor (AR) inhibition is standard of care for advanced prostate cancer (PC). However, efficacy is limited by progression to castration-resistant PC (CRPC), usually due to AR re-activation via mechanisms that include AR amplification and structural rearrangement. These two classes of AR alterations often co-occur in CRPC tumors, but it is unclear whether this reflects intercellular or intracellular heterogeneity of AR. Resolving this is important for developing new therapies and predictive biomarkers. Here, we analyzed 41 CRPC tumors and 6 patient-derived xenografts (PDXs) using linked-read DNA-sequencing, and identified 7 tumors that developed complex, multiply-rearranged AR gene structures in conjunction with very high AR copy number. Analysis of PDX models by optical genome mapping and fluorescence in situ hybridization showed that AR residing on extrachromosomal DNA (ecDNA) was an underlying mechanism, and was associated with elevated levels and diversity of AR expression. This study identifies co-evolution of AR gene copy number and structural complexity via ecDNA as a mechanism associated with endocrine therapy resistance.
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