| 1. |
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| 2. |
- 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. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
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| 6. |
- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
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Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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| 7. |
- Zheng, Jing-Jing, et al.
(författare)
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Electronic structure and phase stability of plutonium hydrides : Role of Coulomb repulsion and spin-orbital coupling
- 2014
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Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 39:25, s. 13255-13265
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Tidskriftsartikel (refereegranskat)abstract
- The electronic and magnetic states, chemical bonding and reactions, and phonon spectrum of the plutonium hydrides Puliz (x = 2, 3) are investigated by employing first-principles calculations by means of the density functional theory (DFT) + U approach. The strong correlation and the spin-orbit coupling (sac) effects on these 5f electrons systems are systematically studied. Results show that both the strong correlation and the SOC play critical roles in correctly describing their ground-state properties. The antiferromagnetic configuration of PuH2 is found energetically most stable while for PuH3 the ferromagnetic state is the most stable state. Our calculated phonon spectra clearly indicate the dynamical stability of these magnetic configurations. For PuH3, more electrons from the Pu atoms are released to bond with H than that in PuH2. As a result, the lattice constant is contracted by increasing the H concentration. Reacting from metal Pu and molecule H-2, more PuH3 should be produced than PuH2 in low temperature condition. Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.
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| 8. |
- Abraham, Roshan Mammen, et al.
(författare)
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Tau neutrinos in the next decade : from GeV to EeV
- 2022
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Ingår i: Journal of Physics G. - : Institute of Physics Publishing (IOPP). - 0954-3899 .- 1361-6471. ; 49:11
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Tidskriftsartikel (refereegranskat)abstract
- Tau neutrinos are the least studied particle in the standard model. This whitepaper discusses the current and expected upcoming status of tau neutrino physics with attention to the broad experimental and theoretical landscape spanning long-baseline, beam-dump, collider, and astrophysical experiments. This whitepaper was prepared as a part of the NuTau2021 Workshop.
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| 9. |
- An, Di, et al.
(författare)
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Additive manufacturing and characterization of complex Al2O3 parts based on a novel stereolithography method
- 2017
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Ingår i: International Journal of Applied Ceramic Technology. - : Wiley. - 1546-542X .- 1744-7402. ; 14:5, s. 836-844
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we prepared Al2O3 ceramic green parts with complex geometry and architecture using an additive manufacturing process based on stereolithography. The rheological and thermal behavior of Al2O3 slurry was firstly examined and used to establish the conditions for molding and debinding. As opposed to previous researches that only focused on manufacture techniques, the sintering behavior and densification process were systematically investigated. In addition, special attentions were paid to the evolution of microstructure between green bodies and sintered parts. The results showed that debound parts were equipped with uniform particle packing and narrow pore size distribution. The dimensions of the Al2O3 parts changed anisotropically with the different processing steps. The densification process was greatly accelerated by the decrease in pore size and annihilating of interconnected pores in which significant grain growth was observed above 1450 degrees C. The sintered part also had a homogeneous microstructure and no interface between adjacent layers. High densification (relative density of 99.1%) and much desirable Vickers hardness (17.9 GPa) of Al2O3 parts were achieved at the sintering temperature of 1650 degrees C.
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| 10. |
- Arndt, D. S., et al.
(författare)
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State of the Climate in 2016
- 2017
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
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Tidskriftsartikel (refereegranskat)abstract
- In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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| 11. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 12. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 13. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 14. |
- Bodén, Andreas, et al.
(författare)
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Conductivity of SDC and (Li/Na)2CO3 composite electrolytes in reducing and oxidising atmospheres
- 2007
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 172:2, s. 520-529
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Tidskriftsartikel (refereegranskat)abstract
- Composite electrolytes made of samarium-doped cerium oxide and a mixture of lithium carbonate and sodium carbonate salts are investigated with respect to their structure, morphology and ionic conductivity. The composite electrolytes are considered promising for use in so called intermediate temperature solid oxide fuel cells (IT-SOFC), operating at 400-600 degrees C. The electrolytes are tested in both gaseous anode (reducing) and cathode (oxidising) environments and at different humidities and carbon dioxide partial pressures. For the structure and morphology measurements, it was concluded that no changes occur to the materials after usage. From measurements of melting energies, it was concluded that the melting point of the carbonate salt phase decreases with decreasing fraction of carbonate salt and that a partial melting occurs before the bulk melting point of the salt is reached. For all the composites, two regions may be observed for the conductivity, one below the carbonate salt melting point and one above the melting point. The conductivity is higher when electrolytes are tested in anode gas than when tested in cathode gas, at least for electrolytes with less than half the volume fraction consisting of carbonate salt. The higher the content of carbonate salt phase, the higher the conductivity of the composite for the temperature region above the carbonate melting point. Below the melting point, though, the conductivity does not follow this trend. Calculations on activation energies for the conductivity show no trend or value that indicates a certain transport mechanism for ion transport, either when changing between the different composites or between different gas environments.
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| 15. |
- Chang, Lei, et al.
(författare)
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Environmental harshness and unpredictability, life history, and social and academic behavior of adolescents in nine countries.
- 2019
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Ingår i: Developmental Psychology. - : American Psychological Association (APA). - 0012-1649 .- 1939-0599. ; 55:4, s. 890-903
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Tidskriftsartikel (refereegranskat)abstract
- Safety is essential for life. To survive, humans and other animals have developed sets of psychological and physiological adaptations known as life history (LH) tradeoff strategies in response to various safety constraints. Evolutionarily selected LH strategies in turn regulate development and behavior to optimize survival under prevailing safety conditions. The present study tested LH hypotheses concerning safety based on a 6-year longitudinal sample of 1,245 adolescents and their parents from 9 countries. The results revealed that, invariant across countries, environmental harshness, and unpredictability (lack of safety) was negatively associated with slow LH behavioral profile, measured 2 years later, and slow LH behavioral profile was negatively and positively associated with externalizing behavior and academic performance, respectively, as measured an additional 2 years later. These results support the evolutionary conception that human development responds to environmental safety cues through LH regulation of social and learning behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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| 16. |
- Chang, Lei, et al.
(författare)
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External environment and internal state in relation to life-history behavioural profiles of adolescents in nine countries
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1917
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Tidskriftsartikel (refereegranskat)abstract
- The external environment has traditionally been considered as the primary driver of animal life history (LH). Recent research suggests that animals' internal state is also involved, especially in forming LH behavioural phenotypes. The present study investigated how these two factors interact in formulating LH in humans. Based on a longitudinal sample of 1223 adolescents in nine countries, the results show that harsh and unpredictable environments and adverse internal states in childhood are each uniquely associated with fast LH behavioural profiles consisting of aggression, impulsivity, and risk-taking in adolescence. The external environment and internal state each strengthened the LH association of the other, but overall the external environment was more predictive of LH than was the internal state. These findings suggest that individuals rely on a multitude and consistency of sensory information in more decisively calibrating LH and behavioural strategies.
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| 17. |
- Desjardins, Kewin, et al.
(författare)
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Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
- 2019
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Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
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Konferensbidrag (refereegranskat)abstract
- A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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| 18. |
- Di Baldassarre, Giuliano, et al.
(författare)
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Sociohydrology : Scientific Challenges in Addressing the Sustainable Development Goals
- 2019
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Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; 55:8, s. 6327-6355
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Tidskriftsartikel (refereegranskat)abstract
- The Sustainable Development Goals (SDGs) of the United Nations Agenda 2030 represent an ambitious blueprint to reduce inequalities globally and achieve a sustainable future for all mankind. Meeting the SDGs for water requires an integrated approach to managing and allocating water resources, by involving all actors and stakeholders, and considering how water resources link different sectors of society. To date, water management practice is dominated by technocratic, scenario-based approaches that may work well in the short term but can result in unintended consequences in the long term due to limited accounting of dynamic feedbacks between the natural, technical, and social dimensions of human-water systems. The discipline of sociohydrology has an important role to play in informing policy by developing a generalizable understanding of phenomena that arise from interactions between water and human systems. To explain these phenomena, sociohydrology must address several scientific challenges to strengthen the field and broaden its scope. These include engagement with social scientists to accommodate social heterogeneity, power relations, trust, cultural beliefs, and cognitive biases, which strongly influence the way in which people alter, and adapt to, changing hydrological regimes. It also requires development of new methods to formulate and test alternative hypotheses for the explanation of emergent phenomena generated by feedbacks between water and society. Advancing sociohydrology in these ways therefore represents a major contribution toward meeting the targets set by the SDGs, the societal grand challenge of our time. Plain Language Summary Water crises that humanity faces are increasingly connected and are growing in complexity. As such, they require a more integrated approach in managing water resources, which involves all actors and stakeholders and considers how water resources link different sectors of society. Yet, water management practice is still dominated by technocratic approaches, which emphasize technical solutions. While these approaches may work in the short-term, they often result in unintended consequences in the long-term. Sociohydrology is developing a generalizable understanding of the interactions and feedbacks between natural,technical and social processes, which can improve water management practice. As such, advancing sociohydrology can contribute to address the global water crises and meet the water-related targets defined by the United Nations' Sustainable Development Goals.
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| 19. |
- Di, Jing, et al.
(författare)
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A novel composite electrolyte based on CeO2 for low temperature solid oxide fuel cells
- 2008
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Ingår i: Journal of Inorganic Materials. - 1000-324X. ; 23:3, s. 573-577
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Tidskriftsartikel (refereegranskat)abstract
- A novel composite material based on mixture of samarium-doped ceria (SDC)-carbonate was studied as electrolyte in low temperature solid oxide fuel cells. The phase and microstructures of composite electrolyte were examined by XRD and SEM. The electrical conductivity was investigated by AC impedance spectroscopy at 400-700 degrees C in different atmospheres. An abrupt change in the conductivity at about 500 degrees C indicates that different mechanisms affect transfer in different temperature ranges. The conductivity increases with the carbonate fraction above 500 degrees C. The conductivity in reduce atmosphere is higher than that in oxide atmosphere. An anode-supported fuel cell using SDC-carbonate as electrolyte was fabricated and tested. The result shows that all the composite electrolytes exhibit better performance than pure SDC electrolyte. The electrolyte with 20wt% carbonate can achieve the highest power density of 415mW center dot cm(-2) and an open circuit voltage of 1.00V at 500 degrees C.
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| 20. |
- Di, Jing, et al.
(författare)
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Samarium doped ceria-(Li/Na)(2)CO3 composite electrolyte and its electrochemical properties in low temperature solid oxide fuel cell
- 2010
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 195:15, s. 4695-4699
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Tidskriftsartikel (refereegranskat)abstract
- A composite of samarium doped ceria (SDC) and a binary carbonate eutectic (52 mol% Li2CO3/48 mol% Na2CO3) is investigated with respect to its morphology, conductivity and fuel cell performances. The morphology study shows the composition could prevent SDC particles from agglomeration. The conductivity is measured under air, argon and hydrogen, respectively. A sharp increase in conductivity occurs under all the atmospheres, which relates to the superionic phase transition in the interface phases between SDC and carbonates. Single cells with the composite electrolyte are fabricated by a uniaxial die-press method using NiO/electrolyte as anode and lithiated NiO/electrolyte as cathode. The cell shows a maximum power density of 590 mW cm(-2) at 600 degrees C, using hydrogen as the fuel and air as the oxidant. Unlike that of cells based on pure oxygen ionic conductor or pure protonic conductor, the open circuit voltage of the SDC-carbonate based fuel cell decreases with an increase in water content of either anodic or cathodic inlet gas, indicating the electrolyte is a co-ionic (H+/O2-) conductor. The results also exhibit that oxygen ionic conductivity contributes to the major part of the whole conductivity under fuel cell circumstances. (C) 2010 Elsevier B.V. All rights reserved.
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| 21. |
- Engebretsen, Elisabeth Lund, et al.
(författare)
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Feminist Activism
- 2019
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Ingår i: Savinetti, N. (ed.) Gendered Dimensions of Welfare in China and the Nordic Region. Feminist transformations, visions and recommendations.. - Copenhagen : NIAS – Nordic Institute of Asian Studies Report. ; , s. 13-16
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 22. |
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| 23. |
- Fan, Liangdong, 1985-, et al.
(författare)
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Potential low-temperature application and hybrid-ionic conducting property of ceria-carbonate composite electrolytes for solid oxide fuel cells
- 2011
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Ingår i: International journal of hydrogen energy. - : Elsevier BV. - 0360-3199 .- 1879-3487. ; 36:16, s. 9987-9993
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Tidskriftsartikel (refereegranskat)abstract
- Ceria-carbonate composite materials have been widely investigated as candidate electrolytes for solid oxide fuel cells operated at 300-600 degrees C. However, fundamental studies on the composite electrolytes are still in the early stages and intensive research is demanded to advance their applications. In this study, the crystallite structure, microstructure, chemical activity, thermal expansion behavior and electrochemical properties of the samaria doped ceria-carbonate (SCC) composite have been investigated. Single cells using the SCC composite electrolyte and Ni-based electrodes were assembled and their electrochemical performances were studied. The SCC composite electrolyte exhibits good chemical compatibility and thermal-matching with Ni-based electrodes. Peak power density up to 916 mW cm(-2) was achieved at 550 degrees C, which was attributed to high electrochemical activity of both electrolyte and electrode materials. A stable discharge plateau was obtained under a current density of 1.5 A cm(-2) at 550 degrees C for 120 min. In addition, the ionic conducting property of the SCC composite electrolyte was investigated using electrochemical impedance spectroscopy technique. It was found that the hybrid-ionic conduction improves the total ionic conductivity and fuel cell performance. These results highlight potential low-temperature application of ceria-carbonate composite electrolytes for solid oxide fuel cells.
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| 24. |
- Fan, Liangdong, et al.
(författare)
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Proton and Oxygen Ionic Conductivity of Doped Ceria-Carbonate Composite by Modified Wagner Polarization
- 2012
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Ingår i: International Journal of Electrochemical Science. - 1452-3981. ; 7:9, s. 8420-8435
-
Tidskriftsartikel (refereegranskat)abstract
- The impressive ionic conductivity and tunable conduction behaviors have made the ceria-carbonate composite an attractive electrolyte for low temperature ceramic fuel cells. However, the conduction mechanism is not yet well studied. In the present study, both proton and oxygen ion conductivity as well as the transport properties of samaria-doped ceria/ sodium-lithium-carbonate (denoted as SDCLN) composite are investigated by the fuel cell study and the modified Hebb-Wagner polarization measurements. The multi-ionic polarization behaviors and the transfer processes in composite electrolyte under external electrical field are analyzed. A maximum power density of 780 mW cm(-2) and a calculated total ion (proton and oxygen ion) conductivity of 0.153 S cm(-1) are obtained under H-2/air condition at 550 degrees C. The Wagner DC polarization measurements show that the proton conduction dominates the total ionic conductivity. A synergistic effect exists between the charge carriers in the doped ceria-carbonate composite system. An ideal interfacial conduction model is also proposed based on the obtained results.
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| 25. |
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| 26. |
- Gaziano, Liam, et al.
(författare)
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Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19
- 2021
-
Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4
-
Tidskriftsartikel (refereegranskat)abstract
- Large-scale Mendelian randomization and colocalization analyses using gene expression and soluble protein data for 1,263 actionable druggable genes, which encode protein targets for approved drugs or drugs in clinical development, identify IFNAR2 and ACE2 as the most promising therapeutic targets for early management of COVID-19. Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. We found significant Mendelian randomization results for three proteins (ACE2, P = 1.6 x 10(-6); IFNAR2, P = 9.8 x 10(-11) and IL-10RB, P = 2.3 x 10(-14)) using cis-expression quantitative trait loci genetic instruments that also had strong evidence for colocalization with COVID-19 hospitalization. To disentangle the shared expression quantitative trait loci signal for IL10RB and IFNAR2, we conducted phenome-wide association scans and pathway enrichment analysis, which suggested that IFNAR2 is more likely to play a role in COVID-19 hospitalization. Our findings prioritize trials of drugs targeting IFNAR2 and ACE2 for early management of COVID-19.
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| 27. |
- Griesmayer, E., et al.
(författare)
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Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
- 2019
-
Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
-
Konferensbidrag (refereegranskat)abstract
- Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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| 28. |
- Jin, Chuan, 1986-, et al.
(författare)
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CAR T cells expressing a bacterial virulence factor trigger potent bystander antitumour responses in solid cancers
- 2022
-
Ingår i: Nature Biomedical Engineering. - : Springer Nature. - 2157-846X. ; 6:7, s. 830-841
-
Tidskriftsartikel (refereegranskat)abstract
- Chimeric antigen receptor T cells (CAR T cells) are effective against haematologic malignancies. However, in solid tumours, their potency is hampered by local immunosuppression and by the heterogeneous expression of the antigen that the CAR targets. Here we show that CAR T cells expressing a pluripotent pro-inflammatory neutrophil-activating protein (NAP) from Helicobacter pylori trigger endogenous bystander T-cell responses against solid cancers. In mice with subcutaneous murine pancreatic ductal adenocarcinomas, neuroblastomas or colon carcinomas, CAR(NAP) T cells led to slower tumour growth and higher survival rates than conventional mouse CAR T cells, regardless of target antigen, tumour type and host haplotype. In tumours with heterogeneous antigen expression, NAP secretion induced the formation of an immunologically 'hot' microenvironment that supported dendritic cell maturation and bystander responses, as indicated by epitope spreading and infiltration of cytotoxic CD8(+) T cells targeting tumour-associated antigens other than the CAR-targeted antigen. CAR T cells armed with NAP neither increased off-tumour toxicity nor hampered the efficacy of CAR T cells, and hence may have advantageous translational potential. T cells expressing a pluripotent pro-inflammatory neutrophil-activating protein from Helicobacter pylori trigger endogenous bystander T-cell responses against solid cancers.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 33. |
- Li, Hui, et al.
(författare)
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Enabling the transition to ductile MAX phases and the exfoliation to MXenes via tuning the A element
- 2023
-
Ingår i: Journal of The American Ceramic Society. - : Wiley-Blackwell. - 0002-7820 .- 1551-2916. ; 106:6, s. 3765-3776
-
Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional MXenes, exfoliated from their parental precursors-MAX phases, exhibit several outstanding properties and have achieved several accomplishments in a vast range of fields. Developing novel and high-performance MXenes has become a vital task in materials science, so estimating the possibilities for exfoliation is a topic positioned at the research frontier. Here, the likelihood of exfoliating 36 M(2)AC MAX phases was explored by using density functional theory. For MAX phases, the composition-dependent mechanical performances were investigated, highlighting evident trends, and, more essentially, improving MAX phases toughness, which can be achieved via modulating the A site. Two novel criteria were then introduced to assess the probability of exfoliating MXenes from MAX phases, having less complexity and lower computational cost than the prior studies. The excellent agreement provided by the new criteria with the reported results demonstrates that they are feasible, reliable as well as easily accessible. Furthermore, some key features that were previously suggested to be related to exfoliation are instead determined to be weakly correlated with it. We thus performed a detailed numerical analysis to locate representative and correlated features that are fundamental for the exfoliation. Our findings provide deep insight into the synthesis process and accelerate the discovery of new MXenes.
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| 34. |
- Li, Yuhan, et al.
(författare)
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Understanding the electrochemical properties of A(2)MSiO(4) (A = Li and Na; M = Fe, Mn, Co and Ni) and the Na doping effect on Li2MSiO4 from first-principles calculations
- 2016
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Ingår i: Journal of Materials Chemistry A. - : Royal Society of Chemistry (RSC). - 2050-7488 .- 2050-7496. ; 4:44, s. 17455-17463
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Tidskriftsartikel (refereegranskat)abstract
- To explore the feasibility of regarding silicate materials as sustainable cathode materials for rechargeable Na ion batteries, the voltage plateaus, cycling stabilities, electrical conductivities and ionic conductivities of Li2MSiO4 and Na2MSiO4 (M = Fe, Mn, Co and Ni) are investigated by first principles calculations. The calculated electrochemical performance of silicate materials gives reasonable explanations for the poor capacity retention of Li2MnSiO4 as well as the reason why Li2FeSiO4 and Li2CoSiO4 exchange only one Li ion per formula unit. In comparison with Na2MSiO4, Li2MSiO4 presents higher voltage and better cycling stability. However, Na2MSiO4 displays higher electrical and ionic conductivities. Moreover, Na2NiSiO4 also presents significant potential for application as a good cathode material for Na ion batteries, as it can deliver high voltage and reversibly exchange 1.5 Li ions per formula unit. Furthermore, to make full use of the advantages of Li2MSiO4 and Na2MSiO4, a Na doped Li1.5Na0.5MSiO4 system is explored as well. The results suggest that Na doping can improve the electronic and ionic conductivities of Li2MSiO4 materials and simultaneously maintain the voltage and cycling stability. Therefore, Na ion doping should be an effective methodology to improve the performance of Li2MSiO4 cathode materials.
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| 35. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
-
Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 36. |
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| 37. |
- Ma, Jing
(författare)
-
Cancer Immunotherapy : Oncolytic viruses and CAR-T cells
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Various forms of cancer immunotherapy have developed rapidly with improved survival and quality of life for cancer patients. Cancer immunotherapy aims to educate the patient’s immune system to eliminate cancer cells, including immune checkpoint inhibitors (ICIs), adoptive cell transfer (mostly T cells), oncolytic viruses (OVs) and cancer vaccines. Especially ICIs have induced durable responses in patients with many different types of cancers. Chimeric antigen receptor (CAR)-T cell therapy has shown good efficacy in treating hematologic malignancies. However, there is still a significant number of patients that do not benefit from these treatments due to immune evasion. Strategies to modify cancer immunotherapies with immunomodulating agent needs to be investigated to maximize the effect of immunotherapy. Helicobacter pylori Neutrophil Activating Protein (HP-NAP) could be used as an immunomodulating agent to recruit, activate and mature immune cells, such as dendritic cells (DCs), monocytes and neutrophils, and also induce T helper type 1 (Th1)-polarized response. In this thesis, we examined to arm oncolytic virus or CAR-T cells with HP-NAP.Papers I and II investigate oncolytic viruses. In paper I, we investigated wild-type Adenovirus (Ad), Semliki forest virus (SFV) and Vaccinia virus (VV), for their ability to mediate lysis of tumor cells, which was found to be associated with the release of danger-associated molecular patterns (DAMPs) and subsequently triggered phagocytosis and maturation of DCs. However, only SFV-infected tumor cells triggered significant Th1-cytokine release by DCs and induced antigen-specific T cell activation, while VV induced immunosuppressive responses. In Paper II, we armed VV and SFV with the tumor-associated antigen GD2 and HP-NAP. We found that arming these OVs with HP-NAP resulted in distinct anti-tumor immune response and therapeutic benefit. VV-GD2m-NAP showed significantly increased therapeutic efficacy compared to VV-GD2m, associated with elevated antiGD2 antibody production. In contrast, there was no additive antitumor effect for SFV-GD2m-NAP compared with SFV-GD2m. Due to intrinsic properties of OVs, engineering OVs with immunomodulating agents needs careful consideration. Engineering SFV or similar viruses, which is very immunogenic, should focus on improving oncolysis, de-bulking tumor and release of tumor-associated antigens, while for VV or similar viruses, with immunosuppressive properties, the focus can be on arming the virus with immune modulators to improve anti-tumor immune response. Papers III and IV investigate CAR-T cells. In paper III, CAR-T cells were engineered to inducible secrete HP-NAP upon antigen recognition (CAR(NAP)-Ts). CAR(NAP)-Ts successfully reduced tumor growth and prolonged survival of mice in several solid tumor models with epitope spreading and initiated endogenous anti-tumor immune responses. Secreted HP-NAP created an immunologically hot tumor microenvironment with enhanced infiltration of immune cells (DCs, neutrophils, macrophages, and cytotoxic natural killer cells). In paper IV, we developed CAR T cells targeting CD20 (rituCD20CAR T cells). We found that rituCD20CAR T cells could efficiently kill CD20-positive lymphoma cell lines (U2932, Karpas422, DB, U698, Raji, Daudi) as well as primary mantle cell CD20-positive lymphoma (CD20+ MCL) cells accompanying with IFNγ secretion. Both rituCD20CAR and NAP-armed rituCD20CAR(NAP) T-cell treatment delayed tumor growth and prolonged mice survival in the murine lymphoma A20-hCD20 model. In summary, combing OVs and CAR-T cells with the immunomodulating agent HP-NAP is a promising way of maximizing the benefit of immunotherapy to combat cancers.
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| 38. |
- Ma, Jing, et al.
(författare)
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Characterization of virus-mediated immunogenic cancer cell death and the consequences for oncolytic virus-based immunotherapy of cancer
- 2020
-
Ingår i: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Oncolytic viruses have the potential to induce immunogenic cell death (ICD) that may provoke potent and long-lasting anti-cancer immunity. Here we aimed to characterize the ICD-inducing ability of wild-type Adenovirus (Ad), Semliki Forest virus (SFV) and Vaccinia virus (VV). We did so by investigating the cell death and immune-activating properties of virus-killed tumor cells. Ad-infection of tumor cells primarily activates autophagy, but also activate events of necroptotic and pyroptotic cell death. SFV infection on the other hand primarily activates immunogenic apoptosis while VV activates necroptosis. All viruses mediated lysis of tumor cells leading to the release of danger-associated molecular patterns, triggering of phagocytosis and maturation of dendritic cells (DCs). However, only SFV-infected tumor cells triggered significant T helper type 1 (Th1)-cytokine release by DCs and induced antigen-specific T-cell activation. Our results elucidate cell death processes activated upon Ad, SFV, and VV infection and their potential to induce T cell-mediated anti-tumor immune responses. This knowledge provides important insight for the choice and design of therapeutically successful virus-based immunotherapies.
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| 39. |
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| 40. |
- Ma, Jing, et al.
(författare)
-
Concurrent expression of HP-NAP enhances antitumor efficacy of oncolytic vaccinia virus but not for Semliki Forest virus
- 2021
-
Ingår i: MOLECULAR THERAPY-ONCOLYTICS. - : Cell Press. - 2372-7705. ; 21, s. 356-366
-
Tidskriftsartikel (refereegranskat)abstract
- Oncolytic viruses (OVs) represent promising therapeutic agents for cancer therapy by selective oncolysis and induction of anti-tumor immunity. OVs can be engineered to express tumor-associated antigens and immune-modulating agents to provoke stronger antitumor immunity. Here, we engineered vaccinia virus (VV) and Semliki Forest virus (SFV) to express neuroblastoma-associated antigen disialoganglioside (GD2) and the immune modulator Helicobacter pylori neutrophil-activating protein (NAP) and compared their therapeutic potency. Oncolytic VV did not exhibit any antitumor benefits, whereas SFV was able to delay subcutaneous neuroblastoma (NXS2) tumor growth. Additional expression of the GD2 mimotope (GD2m) by VV-GD2m or SFV-GD2m did not improve their anti-tumor capacity compared to the parent viruses. Further arming these OVs with NAP resulted in contrasting anti-tumor efficacy. VV (VV-GD2m-NAP) significantly improved therapeutic efficacy compared to VV-GD2m, which was also associated with a significantly elevated anti-GD2 antibody, whereas there was no additive antitumor efficacy for SFV-GD2m-NAP compared to SFV-GD2m, nor was the anti-GD2 antibody response improved. Instead, NAP induced higher neutralizing antibodies against SFV. These observations suggest that distinct immune stimulation profiles are elicited when the same immunostimulatory factor is expressed by different OVs. Therefore, careful consideration and detailed characterization are needed when engineering OVs with immune-modulators.
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| 41. |
- Marcouille, O., et al.
(författare)
-
Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
- 2019
-
Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
-
Konferensbidrag (refereegranskat)abstract
- Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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| 42. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 43. |
- Martikainen, Miika, et al.
(författare)
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IFN-I-tolerant oncolytic Semliki Forest virus in combination with anti-PD1 enhances T cell response against mouse glioma
- 2021
-
Ingår i: MOLECULAR THERAPY-ONCOLYTICS. - : Cell Press. - 2372-7705. ; 21, s. 37-46
-
Tidskriftsartikel (refereegranskat)abstract
- Oncolytic virotherapy holds promise of effective immunotherapy against otherwise nonresponsive cancers such as glioblastoma. Our previous findings have shown that although oncolytic Semliki Forest virus (SFV) is effective against various mouse glioblastoma models, its therapeutic potency is hampered by type I interferon (IFN-I)-mediated antiviral signaling. In this study, we constructed a novel IFN-I-resistant SFV construct, SFV-AM6, and evaluated its therapeutic potency in vitro, ex vivo, and in vivo in the IFN-I competent mouse GL261 glioma model. In vitro analysis shows that SFV-AM6 causes immunogenic apoptosis in GL261 cells despite high IFN-I signaling. MicroRNA-124 de-targeted SFV-AM6-124T selectively replicates in glioma cells, and it can infect orthotopic GL261 gliomas when administered intraperitoneally. The combination of SFV-AM6-124T and anti-programmed death 1 (PD1) immunotherapy resulted in increased immune cell infiltration in GL261 gliomas, including an increased tumor-reactive CD8(+) fraction. Our results show that SFV-AM6-124T can overcome hurdles of innate anti-viral signaling. Combination therapy with SFV-AM6-124T and antiPD1 promotes the inflammatory response and improves the immune microenvironment in the GL261 glioma model.
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| 44. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 45. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
-
Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 46. |
- Plivelic, Tomás S., et al.
(författare)
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X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
- 2019
-
Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
-
Konferensbidrag (refereegranskat)abstract
- A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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| 47. |
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| 48. |
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| 49. |
- Stone, Rivka C, et al.
(författare)
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Interferon regulatory factor 5 activation in monocytes of systemic lupus erythematosus patients is triggered by circulating autoantigens independent of type I interferons
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 64:3, s. 788-798
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Genetic variants of interferon regulatory factor 5 (IRF-5) are associated with susceptibility to systemic lupus erythematosus (SLE). IRF-5 regulates the expression of proinflammatory cytokines and type I interferons (IFNs) believed to be involved in the pathogenesis of SLE. The aim of this study was to determine the activation status of IRF-5 by assessing its nuclear localization in the immune cells of SLE patients and healthy donors, and to identify SLE-associated triggers of IRF-5 activation. Methods: IRF-5 nuclear localization in subpopulations of peripheral blood mononuclear cells from 14 genotyped SLE patients and 11 healthy controls was assessed using imaging flow cytometry. The activation and function of IRF-5 were examined after ex vivo stimulation of healthy donor monocytes with SLE serum or components of SLE serum. Cellular localization was determined by ImageStream flow cytometry, and cytokine expression was analyzed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results: IRF-5 was activated in a cell type–specific manner; monocytes from SLE patients had constitutively elevated levels of nuclear IRF-5, as compared to natural killer cells and T cells. SLE serum was identified as a trigger for IRF-5 nuclear accumulation; however, neither IFNα nor SLE immune complexes could induce nuclear localization. Instead, autoantigens composed of apoptotic/necrotic material triggered IRF-5 nuclear accumulation in monocytes. Production of the cytokines IFNα, tumor necrosis factor α, and interleukin-6 in monocytes stimulated with SLE serum or autoantigens was distinct, yet showed a correlation with the kinetics of IRF-5 nuclear localization. Conclusion: This study provides the first formal proof that IRF-5 activation is altered in the monocytes of SLE patients, which can be attributed, in part, to the SLE blood environment.
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| 50. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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