| 1. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Tidskriftsartikel (refereegranskat)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
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| 4. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 5. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 6. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Kuzuhara, Masayuki, et al.
(författare)
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Gliese 12 b: A Temperate Earth-sized Planet at 12 pc Ideal for Atmospheric Transmission Spectroscopy
- 2024
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Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 969:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent discoveries of Earth-sized planets transiting nearby M dwarfs have made it possible to characterize the atmospheres of terrestrial planets via follow-up spectroscopic observations. However, the number of such planets receiving low insolation is still small, limiting our ability to understand the diversity of the atmospheric composition and climates of temperate terrestrial planets. We report the discovery of an Earth-sized planet transiting the nearby (12 pc) inactive M3.0 dwarf Gliese 12 (TOI-6251) with an orbital period (P(or)b) of 12.76 days. The planet, Gliese 12 b, was initially identified as a candidate with an ambiguous P-orb from TESS data. We confirmed the transit signal and P-orb using ground-based photometry with MuSCAT2 and MuSCAT3, and validated the planetary nature of the signal using high-resolution images from Gemini/NIRI and Keck/NIRC2 as well as radial velocity (RV) measurements from the InfraRed Doppler instrument on the Subaru 8.2 m telescope and from CARMENES on the CAHA 3.5 m telescope. X-ray observations with XMM-Newton showed the host star is inactive, with an X-ray-to-bolometric luminosity ratio of log L-X/L-bol approximate to - 5.7. Joint analysis of the light curves and RV measurements revealed that Gliese 12 b has a radius of 0.96 +/- 0.05 R-circle plus, a 3 sigma mass upper limit of 3.9M(circle plus), and an equilibrium temperature of 315 +/- 6 K assuming zero albedo. The transmission spectroscopy metric (TSM) value of Gliese 12 b is close to the TSM values of the TRAPPIST-1 planets, adding Gliese 12 b to the small list of potentially terrestrial, temperate planets amenable to atmospheric characterization with JWST.
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| 8. |
- Prieto-Díaz, Rubén, et al.
(författare)
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Exploring the Effect of Halogenation in a Series of Potent and Selective A2B Adenosine Receptor Antagonists
- 2023
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:1, s. 890-912
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Tidskriftsartikel (refereegranskat)abstract
- The modulation of the A2B adenosine receptor is a promising strategy in cancer (immuno) therapy, with A2BAR antagonists emerging as immune checkpoint inhibitors. Herein, we report a systematic assessment of the impact of (di- and mono-)halogenation at positions 7 and/or 8 on both A2BAR affinity and pharmacokinetic properties of a collection of A2BAR antagonists and its study with structure-based free energy perturbation simulations. Monohalogenation at position 8 produced potent A2BAR ligands irrespective of the nature of the halogen. In contrast, halogenation at position 7 and dihalogenation produced a halogen-size-dependent decay in affinity. Eight novel A2BAR ligands exhibited remarkable affinity (Ki < 10 nM), exquisite subtype selectivity, and enantioselective recognition, with some eutomers eliciting sub-nanomolar affinity. The pharmacokinetic profile of representative derivatives showed enhanced solubility and microsomal stability. Finally, two compounds showed the capacity of reversing the antiproliferative effect of adenosine in activated primary human peripheral blood mononuclear cells.
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| 9. |
- Rodriguez-Espigares, Ismael, et al.
(författare)
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GPCRmd uncovers the dynamics of the 3D-GPCRome
- 2020
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Ingår i: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 17:8, s. 777-787
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Tidskriftsartikel (refereegranskat)abstract
- G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
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| 10. |
- Rueda, Blanca, et al.
(författare)
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Analysis of IRF5 gene functional polymorphisms in rheumatoid arthritis
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:12, s. 3815-3819
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Recent findings suggest that interferon regulatory factor 5 (IRF-5) may play a crucial role in several cellular processes, including the transcription of genes for inflammatory cytokines. Two genetic variants of the IRF5 gene (rs2004640 in exon 1 and rs2280714 in the 3'-untranslated region) have been shown to exert functional modifications affecting IRF5 messenger RNA splicing and expression, and have been associated with genetic predisposition to systemic lupus erythematosus (SLE). The aim of this study was to analyze the possible contribution of the IRF5 gene to the predisposition to rheumatoid arthritis (RA). METHODS: Three case-control cohorts from Spain (724 RA patients and 542 healthy controls), Sweden (281 RA patients 474 healthy controls), and Argentina (284 RA patients and 286 healthy controls) were independently analyzed. Genotyping for IRF5 rs2004640 and rs2280714 was performed using a TaqMan 5' allele-discrimination assay. RESULTS: In the 3 cohorts studied, no statistically significant differences in allele or genotype frequencies of the rs2004640 and rs2280714 IRF5 polymorphisms were observed between RA patients and controls. Accordingly, haplotype analysis revealed that none of the IRF5 haplotypes was associated with genetic predisposition to RA. CONCLUSION: Our results suggest that the IRF5 functional polymorphisms analyzed do not seem to be implicated in genetic susceptibility to RA.
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| 11. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 12. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 13. |
- 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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| 14. |
- Azuaje, Jhonny, et al.
(författare)
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Pyrazin-2(1H)-ones as a novel class of selective A3 adenosine receptor antagonists
- 2015
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Ingår i: Future Medicinal Chemistry. - : Future Science Ltd. - 1756-8919 .- 1756-8927. ; 7:11, s. 1373-1380
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Tidskriftsartikel (refereegranskat)abstract
- Background: A(3)AR antagonists are promising drug candidates as neuroprotective agents as well as for the treatment of inflammation or glaucoma. The most widely known A(3)AR antagonists are derived from polyheteroaromatic scaffolds, which usually show poor pharmacokinetic properties. Accordingly, the identification of structurally simple A(3)AR antagonists by the exploration of novel diversity spaces is a challenging goal. Results: A convergent and efficient Ugi-based multicomponent approach enabled the discovery of pyrazin-2(1H)-ones as a novel class of A(3)AR antagonists. A combined experimental/computational strategy accelerated the establishment of the most salient features of the structure-activity and structure-selectivity relationships in this series. Conclusion: The optimization process provided pyrazin-2(1H)-ones with improved affinity and a plausible hypothesis regarding their binding modes was proposed.
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| 15. |
- Barea-Sepulveda, Marta, et al.
(författare)
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Total Ion Chromatogram and Total Ion Mass Spectrum as Alternative Tools for Detection and Discrimination (A Review)
- 2022
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Ingår i: CHEMOSENSORS. - : MDPI AG. - 2227-9040. ; 10:11
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Forskningsöversikt (refereegranskat)abstract
- Gas chromatography (GC) and mass spectrometry (MS) are widely used techniques in the analysis of complex mixtures due to their various advantages, such as high selectivity, reproducibility, precision, and sensitivity. However, the data processing is often complex and time-consuming and requires a great deal of experience, which might be a serious drawback in certain areas, such as quality control, or regarding research in the field of medicine or forensic sciences, where time plays a crucial role. For these reasons, some authors have proposed the use of alternative data processing approaches, such as the total ion chromatogram or total mass spectrum, allowing these techniques to be treated as sensors where each retention time or ratio m/z acts as a sensor collecting total intensities. In this way, the main advantages associated with both techniques are maintained, but the outcomes from the analysis can be reached in a faster, simpler, and an almost automated way. In this review, the main features of the GC- and MS-based analysis methodologies and the ways in which to apply them are highlighted. Moreover, their implementation in different fields, such as agri-food, forensics, environmental sciences, or medicine is discussed, highlighting important advantages as well as limitations.
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| 16. |
- Behera, Nilamani, et al.
(författare)
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Ultra-Low Current 10 nm Spin Hall Nano-Oscillators
- 2024
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Ingår i: Advanced Materials. - 0935-9648 .- 1521-4095. ; 36:5
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Tidskriftsartikel (refereegranskat)abstract
- Nano-constriction based spin Hall nano-oscillators (SHNOs) are at the forefront of spintronics research for emerging technological applications, such as oscillator-based neuromorphic computing and Ising Machines. However, their miniaturization to the sub-50 nm width regime results in poor scaling of the threshold current. Here, it shows that current shunting through the Si substrate is the origin of this problem and studies how different seed layers can mitigate it. It finds that an ultra-thin Al2O3 seed layer and SiN (200 nm) coated p-Si substrates provide the best improvement, enabling us to scale down the SHNO width to a truly nanoscopic dimension of 10 nm, operating at threshold currents below 30 (Formula presented.) A. In addition, the combination of electrical insulation and high thermal conductivity of the Al2O3 seed will offer the best conditions for large SHNO arrays, avoiding any significant temperature gradients within the array. The state-of-the-art ultra-low operational current SHNOs hence pave an energy-efficient route to scale oscillator-based computing to large dynamical neural networks of linear chains or 2Darrays.
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| 17. |
- Behera, Nilamani, et al.
(författare)
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Ultra-low-current Spin Hall Nano-oscillators
- 2023
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Ingår i: 2023 IEEE International Magnetic Conference - Short Papers, INTERMAG Short Papers 2023 - Proceedings. - 9798350338362
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Konferensbidrag (refereegranskat)abstract
- We report on the magnetodynamic properties and the magnetization auto-oscillations of ultra-low current 20 nm width nano-constriction spin Hall nano-oscillators (SHNOs) fabricated on different substrates and seed layers. Combining an optimized W88Ta12 alloy, low damping CoFeB, and a moderate perpendicular magnetic anisotropy, we push the threshold current down to 35 μA in the best devices. The best overall magnetodynamic properties and lowest threshold currents are obtained when using a 3 nm thick AlOx seed layer in between the high-resistance Si substrate and the W88Ta12 layer.
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| 18. |
- Bongers, B. J., et al.
(författare)
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Pan-cancer functional analysis of somatic mutations in G protein-coupled receptors
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- G Protein-coupled receptors (GPCRs) are the most frequently exploited drug target family, moreover they are often found mutated in cancer. Here we used a dataset of mutations found in patient samples derived from the Genomic Data Commons and compared it to the natural human variance as exemplified by data from the 1000 genomes project. We explored cancer-related mutation patterns in all GPCR classes combined and individually. While the location of the mutations across the protein domains did not differ significantly in the two datasets, a mutation enrichment in cancer patients was observed among class-specific conserved motifs in GPCRs such as the Class A "DRY" motif. A Two-Entropy Analysis confirmed the correlation between residue conservation and cancer-related mutation frequency. We subsequently created a ranking of high scoring GPCRs, using a multi-objective approach (Pareto Front Ranking). Our approach was confirmed by re-discovery of established cancer targets such as the LPA and mGlu receptor families, but also discovered novel GPCRs which had not been linked to cancer before such as the P2Y Receptor 10 (P2RY10). Overall, this study presents a list of GPCRs that are amenable to experimental follow up to elucidate their role in cancer.
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| 19. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 20. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 21. |
- Cerecetto, Hugo, et al.
(författare)
-
1, 2, 4-Triazine N-oxide derivatives : studies as potential hypoxic cytotoxins. Part III.
- 2004
-
Ingår i: Archiv der Pharmazie. - : Wiley. - 0365-6233 .- 1521-4184. ; 337:5, s. 271-80
-
Tidskriftsartikel (refereegranskat)abstract
- New 5-(2-arylethenyl)-1, 2, 4-triazine N-oxide and N, N'-dioxide derivatives were synthesized in order to obtain compounds as selective hypoxic cell cytotoxins. The desired products were obtained when the 5-methyl heterocycle reacted with the corresponding iminium electrophiles. The new compounds were tested for their cytotoxicity in oxia and hypoxia. Some of them proved to be less active in hypoxic conditions than Tirapazamine, 3-aminobenzo[1, 2-e]1, 2, 4-triazine N(1), N(4)-dioxide. Derivative 11, 6-methyl-5-[2-(5-nitrofuryl)ethenyl)-1, 2, 4-triazine N(4)-oxide, was the most cytotoxic compound, but it was non-selective. Some derivatives were studied as DNA-binding agents in oxic conditions showing poor affinity for this biomolecule. This result showed that the cytotoxic activity in oxia is DNA damage not dependent. Electrochemical and ESR spectroscopy studies were performed in order to determine the ability of compounds to produce radicals and the relation of these in the mechanism of cytotoxicity.
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| 22. |
- Cerecetto, Hugo, et al.
(författare)
-
1, 2, 4-Triazine N-oxide derivatives : studies as potential hypoxic cytotoxins. Part II.
- 2004
-
Ingår i: Archiv der Pharmazie. - : Weinheim Verlag. - 0365-6233 .- 1521-4184. ; 337:5, s. 247-258
-
Tidskriftsartikel (refereegranskat)abstract
- New 1, 2, 4-Triazine N-oxide and N, N'-dioxide derivatives were synthesized in order to obtain compounds as selective hypoxic cell cytotoxins. The starting heterocycles have been prepared using a standard microwave oven in a clean and good-yielded process. The reactivity of methyl-1, 2, 4-triazine N(4)-oxide and N(1), N(4)-dioxide with different electrophilic agents has been studied. The desired products were obtained only when iminium electrophiles were employed. The regioselectivity of this process has been studied by means of experimental and theoretical (at ab initio level) procedures. Theoretically was expected that the most stable intermediates where the benzylic-like anion from position 5. A fact which agreed with the experimental observed regioselectivity. The new compounds were tested for their cytotoxicity in oxia and hypoxia. Some of them proved to be less active in hypoxic conditions than tirapazamine, 3-amino-benzo[1, 2-e]1, 2, 4-triazine N(1), N(4)-dioxide. Derivative 19, 6-methyl-5-[2-(5-nitrothienyl)ethenyl)-1, 2, 4-triazine N(4)-oxide, was the most cytotoxic compound, but it was non-selective.
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| 23. |
- Consiglio, Camila, et al.
(författare)
-
Immune system adaptation during gender-affirming testosterone treatment
- 2023
-
Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159, s. 29-30
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.
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| 24. |
- El Maatougui, Abdelaziz, et al.
(författare)
-
Discovery of Potent and Highly Selective A(2B) Adenosine Receptor Antagonist Chemotypes
- 2016
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 59:5, s. 1967-1983
-
Tidskriftsartikel (refereegranskat)abstract
- Three novel families of A(2B) adenosine receptor antagonists were identified in the context of the structural exploration of the 3,4-dihydropyrimidin,2(1H)-one chemotype. The most appealing series contain imidazole, 1,2,4-triazole, or benzimidazole rings fused to the 2,3-positions of the parent diazinone core. The optimization process enabled identification of a highly potent (3.49 nM) A(2B) ligand that exhibits complete selectivity toward A(1), A(2A), and A(3) receptors. The results of functional cAMP experiments confirmed the antagonistic behavior of representative ligands. The main SAR trends identified within the series were substantiated by a molecular modeling study based on a receptor-driven docking model constructed on the basis of the crystal structure of the human A(2A) receptor.
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| 25. |
- Faux, Pierre, et al.
(författare)
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Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
- 2023
-
Ingår i: Communications Biology. - 2399-3642. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of similar to 123kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function. Neanderthal-derived variants in the SCN9A gene (encoding the voltage gated sodium channel, Nav1.7) are associated with enhanced experimental mechanical pain sensitivity in modern humans.
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| 26. |
- Garcia-Ruiz, Andres, et al.
(författare)
-
Hermetic Carbon Coatings for Electro-Thermal All-Fiber Phase Modulators
- 2019
-
Ingår i: Journal of Lightwave Technology. - : IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. - 0733-8724 .- 1558-2213. ; 37:18, s. 4567-4572
-
Tidskriftsartikel (refereegranskat)abstract
- Joule effect and thermal response of several carbon-coated fibers are modeled and analyzed. An electro-thermally driven all-fiber phase modulator based on these principles is proposed and a proof of concept of it is characterized. This kind of fiber could be the basis for developing all-fiber components aimed to operate in environments where the strength increase and impermeability to hydrogen diffusion guaranteed by the carbon coating is crucial.
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| 27. |
- Gonzalez, Hugo, et al.
(författare)
-
Cellular architecture of human brain metastases
- 2022
-
Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 185:4, s. 20-745
-
Tidskriftsartikel (refereegranskat)abstract
- Brain metastasis (BrM) is the most common form of brain cancer, characterized by neurologic disability and an abysmal prognosis. Unfortunately, our understanding of the biology underlying human BrMs remains rudimentary. Here, we present an integrative analysis of >100,000 malignant and non-malignant cells from 15 human parenchymal BrMs, generated by single-cell transcriptomics, mass cytometry, and complemented with mouse model- and in silico approaches. We interrogated the composition of BrM niches, molecularly defined the blood-tumor interface, and revealed stromal immunosuppressive states enriched with infiltrated T cells and macrophages. Specific single-cell interrogation of metastatic tumor cells provides a framework of 8 functional cell programs that coexist or anticorrelate. Collectively, these programs delineate two functional BrM archetypes, one proliferative and the other inflammatory, that are evidently shaped through tumor-immune interactions. Our resource provides a foundation to understand the molecular basis of BrM in patients with tumor cell-intrinsic and host environmental traits.
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| 28. |
- González, Victor Hugo, 1993, et al.
(författare)
-
Global Biasing Using a Hardware-Based Artificial Zeeman Term in Spinwave Ising Machines
- 2023
-
Ingår i: 2023 IEEE International Magnetic Conference - Short Papers, INTERMAG Short Papers 2023 - Proceedings. - 9798350338362
-
Konferensbidrag (refereegranskat)abstract
- A spinwave Ising machine (SWIM) is a newly proposed type of time-multiplexed hardware solver for combinatorial optimization that employs feedback coupling and phase sensitive amplification to map an Ising Hamiltonian into phase-binarized propagating spin-wave RF pulses in an Yttrium-Iron-Garnet (YIG) film. In this work, we increase the mathematical complexity of the SWIM by adding a global Zeeman term to a 4-spin MAX-CUT Hamiltonian using a continuous external electrical signal with the same frequency as the spin pulses and phase locked with with one of the two possible states. We are able to induce ferromagnetic ordering in both directions of the spin states despite antiferromagnetic pairwise coupling. Embedding a planar antiferromagnetic spin system in a magnetic field has been proven to increase the complexity of the graph associated to its Hamiltonian and thus this straightforward implementation helps explore higher degrees of complexity as the technology evolves.
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| 29. |
- González, Victor Hugo, 1993, et al.
(författare)
-
Global biasing using a hardware-based artificial Zeeman term in spinwave Ising machines
- 2024
-
Ingår i: APPLIED PHYSICS LETTERS. - 0003-6951 .- 1077-3118. ; 124:9
-
Tidskriftsartikel (refereegranskat)abstract
- A spinwave Ising machine (SWIM) is a recently proposed type of time-multiplexed hardware solver for combinatorial optimization that employs feedback coupling and phase sensitive amplification to map an Ising Hamiltonian into phase-binarized propagating spinwave RF pulses in an Yttrium-Iron-Garnet film. In this work, we increase the mathematical complexity of the SWIM by adding a global Zeeman term to a 4-spin nearest neighbor Hamiltonian using a continuous external electrical signal with the same frequency as the spin pulses and phase locked with one of the two possible states. We are able to induce ferromagnetic ordering in both directions of the spin states despite antiferromagnetic pairwise coupling. Embedding a planar antiferromagnetic spin system in a magnetic field has been proven to increase the complexity of the graph associated with its Hamiltonian, and, thus, this straightforward implementation helps explore higher degrees of complexity in this evolving solver.
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| 30. |
- González, Victor Hugo, 1993, et al.
(författare)
-
Voltage control of frequency and effective damping in nano-constriction-based spin Hall nano-oscillators
- 2023
-
Ingår i: 2023 IEEE International Magnetic Conference - Short Papers, INTERMAG Short Papers 2023 - Proceedings. - 9798350338362
-
Konferensbidrag (refereegranskat)abstract
- Using micromagnetic simulations, we study the tunability of strongly voltage-controlled magnetic anisotropy (VCMA), ΔK = ±200 kJ/m3, in voltage-gated W/CoFeB/MgO based nano-constriction spin Hall nano-oscillators. The VCMA modifies the local magnetic properties such that the magnetodynamics transitions between regimes of i) confinement, ii) tuning, and iii) separation, with qualitatively different behavior. As a consequence, voltage control remains efficient over a very large frequency range, and subsequent manufacturing advances could allow SHNOs to be easily integrated into next-generation electronics for further fundamental studies and industrial applications.
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| 31. |
- González, Victor Hugo, 1993, et al.
(författare)
-
Voltage control of frequency, effective damping, and threshold current in nano-constriction-based spin Hall nano-oscillators
- 2022
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 121:25
-
Tidskriftsartikel (refereegranskat)abstract
- Using micromagnetic simulations, we study the interplay between strongly voltage-controlled magnetic anisotropy (VCMA), Δ K = ±200 kJ/m3, and gate width, w = 10-400 nm, in voltage-gated W/CoFeB/MgO based nano-constriction spin Hall nano-oscillators. The VCMA modifies the local magnetic properties such that the magnetodynamics transitions between regimes of (i) confinement, (ii) tuning, and (iii) separation with qualitatively different behaviors. We find that the strongest tuning is achieved for gate widths of the same size as the constriction width, for which the effective damping can be increased an order of magnitude compared to its intrinsic value. As a consequence, voltage control remains efficient over a very large frequency range, and subsequent manufacturing advances could allow spin Hall nano-oscillators to be easily integrated into next-generation electronics for further fundamental studies and industrial applications.
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| 32. |
- Greenhalgh, David G., et al.
(författare)
-
Surviving Sepsis After Burn Campaign
- 2023
-
Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 49:7, s. 1487-1524
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. Methods: The International Society for Burn Injuries (ISBI) reached out to regional or na-tional burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and out-come" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC parti-cipants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. Results: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for in burn should be on a basis. Conclusion: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients. (c) 2023 Elsevier Ltd and ISBI. All rights reserved.
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| 33. |
- Hagerling, Catharina, et al.
(författare)
-
Immune effector monocyte–neutrophil cooperation induced by the primary tumor prevents metastatic progression of breast cancer
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:43, s. 21704-21714
-
Tidskriftsartikel (refereegranskat)abstract
- Metastatic behavior varies significantly among breast cancers. Mechanisms explaining why the majority of breast cancer patients never develop metastatic outgrowth are largely lacking but could underlie the development of novel immunotherapeutic target molecules. Here we show interplay between nonmetastatic primary breast cancer and innate immune response, acting together to control metastatic progression. The primary tumor systemically recruits IFNγ-producing immune effector monocytes to the lung. IFNγ up-regulates Tmem173/ STING in neutrophils and enhances their killing capacity. The immune effector monocytes and tumoricidal neutrophils target disseminated tumor cells in the lungs, preventing metastatic outgrowth. Importantly, our findings could underlie the development of immunotherapeutic target molecules that augment the function of immune effector monocytes and neutrophils.
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| 34. |
- Krakovka, Sascha, et al.
(författare)
-
Giardia intestinalis thymidine kinase is a high-affinity enzyme crucial for DNA synthesis and an exploitable target for drug discovery
- 2022
-
Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 298:6
-
Tidskriftsartikel (refereegranskat)abstract
- Giardiasis is a diarrheal disease caused by the unicellular parasite Giardia intestinalis, for which metronidazole is the main treatment option. The parasite is dependent on exogenous deoxyribonucleosides for DNA replication and thus is also potentially vulnerable to deoxyribonucleoside analogs. Here, we characterized the G. intestinalis thymidine kinase, a divergent member of the thymidine kinase 1 family that consists of two weakly homologous parts within one polypeptide. We found that the recombinantly expressed enzyme is monomeric, with 100-fold higher catalytic efficiency for thymidine compared to its second-best substrate, deoxyuridine, and is furthermore subject to feedback inhibition by dTTP. This efficient substrate discrimination is in line with the lack of thymidylate synthase and dUTPase in the parasite, which makes deoxy-UMP a dead-end product that is potentially harmful if converted to deoxy-UTP. We also found that the antiretroviral drug azidothymidine (AZT) was an equally good substrate as thymidine and was active against WT as well as metronidazole-resistant G. intestinalis trophozoites. This drug inhibited DNA synthesis in the parasite and efficiently decreased cyst production in vitro, which suggests that it could reduce infectivity. AZT also showed a good effect in G. intestinalis–infected gerbils, reducing both the number of trophozoites in the small intestine and the number of viable cysts in the stool. Taken together, these results suggest that the absolute dependency of the parasite on thymidine kinase for its DNA synthesis can be exploited by AZT, which has promise as a future medication effective against metronidazole-refractory giardiasis.
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| 35. |
- Kumar, Akash, et al.
(författare)
-
Fabrication of voltage-gated spin Hall nano-oscillators
- 2022
-
Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; :4, s. 1432-1439
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate an optimized fabrication process for electric field (voltage gate) controlled nano-constriction spin Hall nano-oscillators (SHNOs), achieving feature sizes of <30 nm with easy to handle ma-N 2401 e-beam lithography negative tone resist. For the nanoscopic voltage gates, we utilize a two-step tilted ion beam etching approach and through-hole encapsulation using 30 nm HfOx. The optimized tilted etching process reduces sidewalls by 75% compared to no tilting. Moreover, the HfOx encapsulation avoids any sidewall shunting and improves gate breakdown. Our experimental results on W/CoFeB/MgO/SiO2 SHNOs show significant frequency tunability (6 MHz V-1) even for moderate perpendicular magnetic anisotropy. Circular patterns with diameter of 45 nm are achieved with an aspect ratio better than 0.85 for 80% of the population. The optimized fabrication process allows incorporating a large number of individual gates to interface to SHNO arrays for unconventional computing and densely packed spintronic neural networks.
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| 36. |
- Litvinenko, Artem, 1989, et al.
(författare)
-
A spinwave Ising machine
- 2023
-
Ingår i: Communications Physics. - 2399-3650. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- Time-multiplexed Coherent Ising Machines (CIMs) have demonstrated promising results in rapidly solving large-scale combinatorial problems. However, CIMs remain relatively large and power-demanding. Here, we demonstrate a spinwave-based Ising machine (SWIM) that due to the low spinwave group velocity allows for sufficient miniaturization and reduced power consumption. The SWIM is implemented using a 10-mm-long 5-mu m-thick Yttrium Iron Garnet film with off-the-shelf microwave components and can support an 8-spin MAX-CUT problem and solve it in less than 4 mu s consuming only 7 mu J. As the SWIM minimizes its energy, we observe that the spin states can demonstrate both uniform and domain-propagation-like switching. The developed SWIM has the potential for substantial further miniaturization with reduction of power consumption, scalability in the number of supported spins, increase of operational speed, and may become a versatile platform for commercially feasible high-performance solvers of combinatorial optimization problems.
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| 37. |
- Litvinenko, Artem, 1989, et al.
(författare)
-
A Spinwave Time-Multiplexed Ising Machine
- 2023
-
Ingår i: 2023 IEEE International Magnetic Conference - Short Papers, INTERMAG Short Papers 2023 - Proceedings. - 9798350338362
-
Konferensbidrag (refereegranskat)abstract
- We present a spinwave-based time-multiplexed Ising Machine (SWIM) where artificial Ising spins are formed with ns-long spinwave RF pulses propagating in a delay line based on 5-μm thick Yttrium Iron Garnet (YIG) film. The phase of artificial Ising spins is binarized using an off-the-shelf phase-sensitive microwave amplifier and the coupling between spins is implemented with microwave delay cables. Thanks to the very low spinwave group velocity, the 7-mm long YIG delay line can host an 8-spin MAX-CUT combinatorial optimization problem and solve it in less than 4 μ while consuming only 7 μJ.
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| 38. |
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| 39. |
- Magalhães, Regina, et al.
(författare)
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Distributed detection of quadratic Kerr effect in silica fibers using chirped-pulse φoTDR
- 2019
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9781510631236 - 9781510631243
-
Konferensbidrag (refereegranskat)abstract
- Monitoring the presence of external electric fields over large distances and detecting losses along power transmission networks, is of extreme importance nowadays due to concerns with environment, efficiency, cost and safety. In this work, we evaluate a method to achieve distributed measurements of the quadratic electro-optic Kerr effect in silica fibers in a distributed way. For this purpose, we integrate a twin-hole fiber filled with BiSn alloy electrodes and monitor its electric-field induced refractive index (RI) change Δn by using a chirped-pulse phase-sensitive OTDR (CP-ΦOTDR). By exploiting its high sensitivity (RI changes of the order of 10-9), we demonstrate that the proposed system is able to detect the intrinsic quadratic electrooptic nonlinearity (the electric Kerr effect) in the fiber, an effect that is usually considered to be too weak to be exploited for practical applications. Additionally, we show that the CP-ΦOTDR is sufficiently sensitive to measure the electric Kerr effect with untreated standard telecommunication fibers under realistic fields.
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| 40. |
- Magalhaes, Regina, et al.
(författare)
-
Fiber-based distributed bolometry
- 2019
-
Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 27:4, s. 4317-4328
-
Tidskriftsartikel (refereegranskat)abstract
- Optical fibers are inherently designed to allow no interaction between the guided light and the surrounding optical radiation. Thus, very few optical fiber-based technologies exist in the field of optical radiation sensing. Accomplishing fully-distributed optical radiation sensing appears then as even more challenging since, on top of the lack of sensitivity explained above, we should add the need of addressing thousands of measurement points in a single, continuous optical cable. Nevertheless, it is clear that there exist a number of applications which could benefit from such a distributed sensing scheme, particularly if the sensitivity was sufficiently high to be able to measure correctly variations in optical radiation levels compatible with the earth surface. Distributed optical radiation sensing over large distances could be employed in applications such as Dynamic Line Rating (DLR), where it is known that solar radiation can be an important limiting factor in energy transmission through overhead power cables, and also in other applications such as thermo-solar energy. In this work, we present the proof-of-concept of the first distributed bolometer based on optical fiber technology and capable of detecting absolute changes of irradiance. The core idea of the system is the use of a special fiber coating with high emissivity (e.g., carbon coating or black paint). The high absorption of these coatings translates into a temperature change that can be read with sufficiently high sensitivity using phase-sensitive reflectometry. To demonstrate the concept, we interrogate distinct black-coated optical fibers using a chirped-pulse ÖOTDR, and we readily demonstrate the detection of light with resolutions in the order of 1% of the reference solar irradiance, offering a high-potential technology for integration in the aforementioned applications.
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| 41. |
- Magalhães, Regina, et al.
(författare)
-
Towards Distributed Measurements of Electric Fields Using Optical Fibers : Proposal and Proof-Of-Concept Experiment.
- 2020
-
Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 20:16
-
Tidskriftsartikel (refereegranskat)abstract
- Nowadays there is an increasing demand for the cost-effective monitoring of potential threats to the integrity of high-voltage networks and electric power infrastructures. Optical fiber sensors are a particularly interesting solution for applications in these environments, due to their low cost and positive intrinsic features, including small size and weight, dielectric properties, and invulnerability to electromagnetic interference (EMI). However, due precisely to their intrinsic EMI-immune nature, the development of a distributed optical fiber sensing solution for the detection of partial discharges and external electrical fields is in principle very challenging. Here, we propose a method to exploit the third-order and second-order nonlinear effects in silica fibers, as a means to achieve highly sensitive distributed measurements of external electrical fields in real time. By monitoring the electric-field-induced variations in the refractive index using a highly sensitive Rayleigh-based CP-φOTDR scheme, we demonstrate the distributed detection of Kerr and Pockels electro-optic effects, and how those can assign a new sensing dimension to optical fibers, transducing external electric fields into visible minute disturbances in the guided light. The proposed sensing configuration, electro-optical time domain reflectometry, is validated both theoretically and experimentally, showing experimental second-order and third-order nonlinear coefficients, respectively, of χ(2) ~ 0.27 × 10-12 m/V and χ(3) ~ 2.5 × 10-22 m2/V2 for silica fibers.
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| 42. |
- Mendoza-Revilla, Javier, et al.
(författare)
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Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
- 2022
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 39:4
-
Tidskriftsartikel (refereegranskat)abstract
- Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
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| 43. |
- Miranda-Pastoriza, Dario, et al.
(författare)
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Exploring Non-orthosteric Interactions with a Series of Potent and Selective A(3) Antagonists
- 2022
-
Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 13:2, s. 243-249
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Tidskriftsartikel (refereegranskat)abstract
- : A library of potent and highly A3AR selective pyrimidinebased compounds was designed to explore non-orthosteric interactions within this receptor. Starting from a prototypical orthosteric A3AR antagonist (ISVY130), the structure-based design explored functionalized residues at the exocyclic amide L1 region and aimed to provide additional interactions outside the A3AR orthosteric site. The novel ligands were assembled through an efficient and succinct synthetic approach, resulting in compounds that retain the A3AR potent and selective profile while improving the solubility of the original scaffold. The experimentally demonstrated tolerability of the L1 region to structural functionalization was further assessed by molecular dynamics simulations, giving hints of the non-orthosteric interactions explored by these series. The results pave the way to explore newly functionalized A3AR ligands, including covalent drugs and molecular probes for diagnostic and delivery purposes.
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| 44. |
- Naseh, Nima, et al.
(författare)
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Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years
- 2022
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Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 119:6, s. 745-752
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Hyperglycemia in very preterm infants is associated with increased morbidity and mortality. We aimed to investigate potential associations between early hyperglycemia, neonatal cerebral magnetic resonance imaging (MRI), and neurodevelopment at 2.5 years.Methods: The study population included 69 infants with gestational age (GA) 22.3-31.9 weeks (n = 29 with GA <28 weeks), born 2011-2014. Plasma glucose concentrations during the first week were checked according to clinical routines. Hyperglycemia was defined as glucose concentrations above 8.3 mmol/L (150 mg/dL) and above 10 mmol/L (180 mg/dL), respectively, categorized as the highest glucose days 0-2, number of days above 8.3 and 10 mmol/L, and prolonged (yes/no) 2 days or more above 8.3 and 10 mmol/L. The MRI analysis included morphological assessment, regional brain volumes, and assessment of apparent diffusion coefficient (ADC). Neurodevelopmental impairment (NDI) developed in 13 of 67 infants with available outcomes, of which 57 were assessed with the Bayley-III. Univariate and multiple linear and logistic regressions were performed with adjustments for GA, birth weight z-scores, and illness severity expressed as days on mechanical ventilation.Results: Hyperglycemia above 8.3 mmol/L and 10 mmol/L was present in 47.8% and 31.9% of the infants. Hyperglycemia correlated independently with lower white matter volume, but not with other regional brain volumes, and was also associated with lower ADC values in white matter. Hyperglycemia also correlated with lower Bayley-III cognitive and motor scores in infants with GA <28 weeks, but there was no significant effect on NDI.Conclusion: Early hyperglycemia is associated with white matter injury and poorer neurodevelopment in very preterm infants.
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| 45. |
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| 46. |
- Orozco, Gisela, et al.
(författare)
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Study of functional variants of the BANK1 gene in rheumatoid arthritis
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:2, s. 372-379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA). METHODS: Four different cohorts were included in the study: 1,080 RA patients and 1,368 healthy controls from Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and 287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls from Mexico. Samples were genotyped for BANK1 single-nucleotide polymorphisms (SNPs) using a TaqMan 5'-allele discrimination assay. Statistical analysis comparing allele and genotype distributions was performed with the chi-square test. RESULTS: We did not find a significant association between RA and the rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in the major alleles among RA patients. Similarly, for rs3733197, there was an increase in the major allele among patients in every cohort. Nevertheless, this skewing reached statistical significance in the Spanish (P = 0.01, odds ratio [OR] 1.17 [95% confidence interval (95% CI) 1.03-1.32]) and Argentinean (P = 0.04, OR 1.31 [95% CI 1.00-1.72]) populations. We found a significant association of rs10516487 (P = 0.005, OR 1.15 [95% CI 1.04-1.28]) and rs3733197 (P = 0.0009, OR 1.17 [95% CI 1.07-1.29]) with RA in the pooled analysis. In a 3-SNP haplotype analysis, we found that the major TGG haplotype was significantly associated with RA (P = 0.005, OR 1.14 [95% CI 1.04-1.25]). In addition, we found a common CAA haplotype that was protective against RA (P = 0.0004, OR 0.82 [95% CI 0.74-0.92]). CONCLUSION: These results suggest that BANK1 SNPs and haplotypes may contribute to RA susceptibility with a low risk.
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| 47. |
- Pereira, Fabio M., et al.
(författare)
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Hybrid Microfluidic Platform for Multifactorial Analysis Based on Electrical Impedance, Refractometry, Optical Absorption and Fluorescence
- 2016
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes the development of a novel microfluidic platform for multifactorial analysis integrating four label-free detection methods: electrical impedance, refractometry, optical absorption and fluorescence. We present the rationale for the design and the details of the microfabrication of this multifactorial hybrid microfluidic chip. The structure of the platform consists of a three-dimensionally patterned polydimethylsiloxane top part attached to a bottom SU-8 epoxy-based negative photoresist part, where microelectrodes and optical fibers are incorporated to enable impedance and optical analysis. As a proof of concept, the chip functions have been tested and explored, enabling a diversity of applications: (i) impedance-based identification of the size of micro beads, as well as counting and distinguishing of erythrocytes by their volume or membrane properties; (ii) simultaneous determination of the refractive index and optical absorption properties of solutions; and (iii) fluorescence-based bead counting.
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| 48. |
- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 49. |
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| 50. |
- Salome, Pedro M. P., et al.
(författare)
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Passivation of Interfaces in Thin Film Solar Cells : Understanding the Effects of a Nanostructured Rear Point Contact Layer
- 2018
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Ingår i: Advanced Materials Interfaces. - : Wiley. - 2196-7350. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Thin film solar cells based in Cu(In,Ga)Se-2 (CIGS) are among the most efficient polycrystalline solar cells, surpassing CdTe and even polycrystalline silicon solar cells. For further developments, the CIGS technology has to start incorporating different solar cell architectures and strategies that allow for very low interface recombination. In this work, ultrathin 350 nm CIGS solar cells with a rear interface passivation strategy are studied and characterized. The rear passivation is achieved using an Al2O3 nanopatterned point structure. Using the cell results, photoluminescence measurements, and detailed optical simulations based on the experimental results, it is shown that by including the nanopatterned point contact structure, the interface defect concentration lowers, which ultimately leads to an increase of solar cell electrical performance mostly by increase of the open circuit voltage. Gains to the short circuit current are distributed between an increased rear optical reflection and also due to electrical effects. The approach of mixing several techniques allows us to make a discussion considering the different passivation gains, which has not been done in detail in previous works. A solar cell with a nanopatterned rear contact and a 350 nm thick CIGS absorber provides an average power conversion efficiency close to 10%.
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