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4. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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5. |
- 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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6. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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8. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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10. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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11. |
- Aad, G., et al.
(författare)
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- 2013
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swepub:Mat__t (refereegranskat)
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12. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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14. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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15. |
- Jiyang, Xie, et al.
(författare)
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Analysis of Key Factors in Heat Demand Prediction with Neural Networks
- 2017
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Ingår i: Energy Procedia. - : Elsevier BV. - 1876-6102. ; 105, s. 2965-2970
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Tidskriftsartikel (refereegranskat)abstract
- The development of heat metering has promoted the development of statistic models for the prediction of heat demand, due to the large amount of available data, or big data. Weather data have been commonly used as input in such statistic models. In order to understand the impacts of direct solar radiance and wind speed on the model performance comprehensively, a model based on Elman neural networks (ENN) was adopted, of which the results can help heat producers to optimize their production and thus mitigate costs. Compared with the measured heat demand, the introduction of wind speed and direct solar radiation has opposite impacts on the performance of ENN and the inclusion of wind speed can improve the prediction accuracy of ENN. However, ENN cannot benefit from the introduction of both wind speed and direct solar radiation simultaneously.
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16. |
- Liu, Yu-peng, et al.
(författare)
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应用酶热生物分析仪快速测量血糖的研究分析
- 2013
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Ingår i: Journal of Clinical and Experimental Medicine. ; 12:8, s. 579-581
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Tidskriftsartikel (refereegranskat)abstract
- Objective To compare the enzyme thermistor bioanalysis equipment with blood glucose meter which is analyzed by automatic biochemical analyzer, validate the correct rate of this equipment. The long-term aim of the project was to develop a prototype for a bedside monitor system for semi-continuous monitoring of the blood glucose concentration. This was made possible by using the special advantage of the thermal sensor technique in combination with the adjustment of flow. Methods 150 patients were collected in our department. The glucose level was determined using a single channel enzyme thermistor device. Then the results were compared with lab biochemistry analysator. Results There was no significant difference between these two methods (P>0.05). The measuring method with single channel enzyme thermistor device is a reliable method in determining blood glucose level. Single channel enzyme thermistor keep a coincidence with automatic biochemical analyzer. The assay cycle time was 3 minutes. Comparative analysis between our device and the clinical system device showed an excellent correlation for 150 patient blood samples. The device was stabile for hundreds of injections over a period of 45 days. Conclusion Determined glucose in whole blood using a single channel Enzyme Thermistor device can be used to assess the severity of an illness and for evaluating therapeutic efficacy. The ability of the device to analyze whole blood without any pretreatment makes it possible to develop real-time analysis.
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17. |
- Ma, Z., et al.
(författare)
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Deep Neural Network-based Impacts Analysis of Multimodal Factors on Heat Demand Prediction
- 2020
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Ingår i: IEEE Transactions on Big Data. - : IEEE. - 2372-2096 .- 2332-7790. ; 6:3, s. 594-605
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of heat demand using artificial neural networks has attracted enormous research attention. Weather conditions, such as direct solar irradiance and wind speed, have been identified as key parameters affecting heat demand. This paper employs an Elman neural network to investigate the impacts of direct solar irradiance and wind speed on the heat demand from the perspective of the entire district heating network. Results of the overall mean absolute percentage error (MAPE) show that direct solar irradiance and wind speed have quite similar impacts. However, the involvement of direct solar irradiance can clearly reduce the maximum absolute deviation when only involving direct solar irradiance and wind speed, respectively. In addition, the simultaneous involvement of both wind speed and direct solar irradiance does not show an obvious improvement of MAPE. Moreover, the prediction accuracy can also be affected by other factors like data discontinuity and outliers.
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18. |
- Ma, Z., et al.
(författare)
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The role of data analysis in the development of intelligent energy networks
- 2017
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Ingår i: IEEE Network. - : Institute of Electrical and Electronics Engineers Inc.. - 0890-8044 .- 1558-156X. ; 31:5, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis plays an important role in the development of intelligent energy networks (IENs). This article reviews and discusses the application of data analysis methods for energy big data. The installation of smart energy meters has provided a huge volume of data at different time resolutions, suggesting data analysis is required for clustering, demand forecasting, energy generation optimization, energy pricing, monitoring and diagnostics. The currently adopted data analysis technologies for IENs include pattern recognition, machine learning, data mining, statistics methods, and so on. However, existing methods for data analysis cannot fully meet the requirements for processing the big data produced by IENs, therefore more comprehensive data analysis methods are needed to handle the increasing amount of data and to mine more valuable information.
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20. |
- Potapov, Anton M., et al.
(författare)
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Global fine-resolution data on springtail abundance and community structure
- 2024
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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21. |
- Wang, Longxin, et al.
(författare)
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Telomere-to-telomere and haplotype-resolved genome assembly of the Chinese cork oak (Quercus variabilis)
- 2023
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Ingår i: Frontiers in Plant Science. - : Frontiers Media S.A.. - 1664-462X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- The Quercus variabilis, a deciduous broadleaved tree species, holds significant ecological and economical value. While a chromosome-level genome for this species has been made available, it remains riddled with unanchored sequences and gaps. In this study, we present a nearly complete comprehensive telomere-to-telomere (T2T) and haplotype-resolved reference genome for Q. variabilis. This was achieved through the integration of ONT ultra-long reads, PacBio HiFi long reads, and Hi-C data. The resultant two haplotype genomes measure 789 Mb and 768 Mb in length, with a contig N50 of 65 Mb and 56 Mb, and were anchored to 12 allelic chromosomes. Within this T2T haplotype-resolved assembly, we predicted 36,830 and 36,370 protein-coding genes, with 95.9% and 96.0% functional annotation for each haplotype genome. The availability of the T2T and haplotype-resolved reference genome lays a solid foundation, not only for illustrating genome structure and functional genomics studies but also to inform and facilitate genetic breeding and improvement of cultivated Quercus species.
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22. |
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23. |
- Xie, Chu Si, et al.
(författare)
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Post-Traumatic Growth during COVID-19 : The Role of Perceived Social Support, Personality, and Coping Strategies
- 2022
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Ingår i: Healthcare. - : MDPI AG. - 2227-9032. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Although many studies on mental health have been conducted among various populations during the COVID-19 pandemic, few studies have focused on post-traumatic growth (PTG) in the general population. The current study aimed to explore whether perceived social support, personality, and coping strategies are associated with PTG in the COVID-19 pandemic period. The study also investigated whether coping strategies mediate the relations between perceived social support, personality, and PTG. A total of 181 participants (Mage = 24) completed the self-report questionnaire online, which was distributed via various online channels, mainly in China and Sweden. The relations between the study variables were examined with correlation analyses and a multiple mediation analysis. Results showed that more than half of the participants (60.8%) reported experiences of PTG during the pandemic. Additionally, perceived social support, personality traits (extraversion, emotional stability, agreeableness, and conscientiousness) and coping strategies (problem-focused coping, emotion-focused coping, and social support coping) were positively correlated with PTG. In addition, coping strategies (problem-focused coping, emotion-focused coping, and avoidance coping) mediated the relations between perceived social support, personality traits and PTG. Theoretical and practical implications of this study are discussed, concluding that the findings of this study have the potential to guide intervention efforts to promote positive change during the pandemic.
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24. |
- Xie, Yan-Hua, et al.
(författare)
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Nuclear Factor-kappaB-Mediated Endothelin Receptor Up-Regulation Increases Renal Artery Contractility in Rats
- 2013
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 113:6, s. 401-410
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Tidskriftsartikel (refereegranskat)abstract
- Increased renal artery contractility leads to renal vasospasm and ischaemia as well as kidney damage. This study was designed to examine the hypothesis that organ culture of renal arteries induces transcriptional up-regulation of endothelin type A (ETA) and type B2 (ETB2) receptors in the smooth muscle cells via activation of nuclear factor-kappaB (NF-B) and subsequently increases renal artery contractility. Rat renal artery segments were organ-cultured for 6 or 24hr to increase endothelin receptor-mediated contraction. To dissect molecular mechanisms involved in this process, inhibitors for NF-B signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and translation (cycloheximide) were used during organ culture. Endothelin receptors were studied using a sensitive myograph (functional contractility), real-time PCR (mRNA analysis) and immunohistochemistry (protein localization). Compared with fresh segments, contractile responses to endothelin-1 (non-selective endothelin receptor agonist) and sarafotoxin 6c (selective ETB receptor agonist) were significantly increased in the segments after 24hr of organ culture; ETB2 receptor-mediated maximal contraction increased from 2.7 +/- 0.5 to 135.3 +/- 5.1 (p<0.001), and potency (pEC(50)) of ETA receptor agonist increased from 8.20 +/- 0.04 to 8.72 +/- 0.07 (p<0.001). This was in parallel with increased corresponding mRNA and protein expression for ETA and ETB2 receptors. BMS345541, MG-132, actinomycin D or cyclohexamide, respectively, suppressed the up-regulation of ETA and ETB2 receptors. Immunostaining performed with specific antibody showed that IB was phosphorylated during organ culture. In conclusion, activation of NF-B mediates up-regulation of ETA and ETB2 receptors and subsequently increases renal artery contractility, which may contribute to renal vasospasm and ischaemia as well as kidney damage.
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25. |
- Xie, Yan-hua, et al.
(författare)
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Up-Regulation of G-Protein-Coupled Receptors for Endothelin and Thromboxane by Lipid-Soluble Smoke Particles in Renal Artery of Rat
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7843 .- 1742-7835. ; 107:4, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- Up-regulation of G-protein-coupled receptors (GPCR) plays key roles in renal hypertension and cardiovascular disease pathogenesis. The present study was designed to examine if lipid-soluble cigarette smoking particles (DSP), nicotine and endotoxin (LPS), induce GPCR up-regulation for thromboxane A(2) (TP), endothelin type A (ETA) and type B (ETB) receptors in renal artery, and if intracellular signal mechanisms are involved. Renal artery segments of rats were exposed to DSP, nicotine or LPS, in organ culture for up to 24 hr. The GPCR-mediated contractions were recorded by using a myograph system. Expression of the GPCR was examined by real-time PCR and immunohistochemistry at mRNA and protein levels. Sarafatoxin 6c (S6c, selective ETB receptor agonist), endothelin-1 (ET-1, non-selective ETA and ETB receptor agonist) and 9,11-Dideoxy-9a,11a-methanoepoxy prostaglandin F-2a (U46619, a TP receptor agonist) induced contractions were significantly increased after the arterial segments exposed to DSP in a concentration-dependent (0.1-0.4 mu l/ml) manner, and S6c also induced a time-dependent contraction, compared to control (dimethyl sulfoxide). This was in parallel with enhanced mRNA expression for ETB receptor but not ETA and TP receptors, while increased protein expression for ETA, ETB and TP receptors was seen. The specific nuclear factor-kappa B (NF-kappa B) signal pathway inhibitor BMS345541 was applied to link DSP effects to the GPCR up-regulation. It totally abolished ETB receptor up-regulation, but not ETA and TP receptor up-regulations. Our results suggest that DSP transcriptionally up-regulated ETB receptor expression in rat renal artery via NF-kappa B signal pathways, whereas up-regulation of ETA and TP receptor-mediated contraction may involve post-transcriptional mechanisms.
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26. |
- Zhang, Qi, et al.
(författare)
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Muscle-like Artificial Molecular Actuators for Nanoparticles
- 2018
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Ingår i: Chem. - : Cell Press. - 2451-9308 .- 2451-9294. ; 4:11, s. 2670-2684
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Tidskriftsartikel (refereegranskat)abstract
- Muscle tissue performs crucial contraction/extension motions that generate mechanical force and work by consuming chemical energy. Inspired by this naturally created biomolecular machine, artificial molecular muscles are designed and synthesized to undertake linear actuation functions. However, most of these muscle-like actuators are performed at large ensembles, while to realize the nanoscale actuation at the single-to few-molecule level remains challenging. Herein, we developed an artificial muscle-like molecular actuator that can reversibly control the proximity of the attached nano-objects, gold nanoparticles, within the single-molecule length level by its stimuli-responsive muscle-like linear contraction/extension motion. The molecular actuation motion is accompanied by an optical signal output resulting from the plasmonic resonance properties of gold nanoparticles. Meanwhile, the thermal noise of the muscle-like molecular actuator can be overcome by integrating the optical signal over a sufficiently long period.
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27. |
- Zhang, Yaping, et al.
(författare)
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Downregulation of Thromboxane A2 Receptor Occurs Mainly via Nuclear Factor-KappaB Signaling Pathway in Rat Renal Artery
- 2017
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Ingår i: Advances in Pharmacological Sciences. - : Hindawi Limited. - 1687-6334 .- 1687-6342. ; 2017
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Tidskriftsartikel (refereegranskat)abstract
- Thromboxane A2 (TXA2) acts on TXA2 receptors (TP) to regulate renal artery blood flow and subsequently contributes to the pathogenesis of renal ischemia. The present study was designed to examine if nuclear factor-kappaB (NF-B) signaling pathway is involved in the downregulation of TP receptors in rat renal artery. Rat renal artery segments were organ cultured for 6 or 24 h. Downregulation of TP receptors was monitored using myograph (contractile function), real-time PCR (receptor mRNA), and immunohistochemistry (receptor protein). Specific inhibitors (MG-132 and BMS345541) for NF-B signaling pathway were used to dissect the underlying molecular mechanisms involved. Compared to fresh (noncultured) segments, organ culture of the renal artery segments for 24 h induced a significant rightward shift of U46619 (TP receptor agonist) contractile response curves (pEC50: 6.89±0.06 versus 6.48±0.04, P<0.001). This decreased contractile response to U46619 was paralleled with decreased TP receptor mRNA and protein expressions in the renal artery smooth muscle cells. Specific inhibitors (MG-132 and BMS345541) for NF-B signaling pathway significantly abolished the decreased TP protein expression and receptor-mediated contractions. In conclusion, downregulation of TP receptors in the renal artery smooth muscle cells occurs mainly via the NF-B signaling pathway.
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