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Sökning: WFRF:(Wacker M) > (2020-2024)

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1.
  • Niemi, MEK, et al. (författare)
  • 2021
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2.
  • Kanai, M, et al. (författare)
  • 2023
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  • Wacker, A, et al. (författare)
  • Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy
  • 2020
  • Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:22, s. 12415-12435
  • Tidskriftsartikel (refereegranskat)abstract
    • The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
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11.
  • Miyake, F., et al. (författare)
  • A Single-Year Cosmic Ray Event at 5410 BCE Registered in 14C of Tree Rings
  • 2021
  • Ingår i: Geophysical Research Letters. - 0094-8276. ; 48:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The annual 14C data in tree rings is an outstanding proxy for uncovering extreme solar energetic particle (SEP) events in the past. Signatures of extreme SEP events have been reported in 774/775 CE, 992/993 CE, and ∼660 BCE. Here, we report another rapid increase of 14C concentration in tree rings from California, Switzerland, and Finland around 5410 BCE. These 14C data series show a significant increase of ∼6‰ in 5411–5410 BCE. The signature of 14C variation is very similar to the confirmed three SEP events and points to an extreme short-term flux of cosmic ray radiation into the atmosphere. The rapid 14C increase in 5411/5410 BCE rings occurred during a period of high solar activity and 60 years after a grand 14C excursion during 5481–5471 BCE. The similarity of our 14C data to previous events suggests that the origin of the 5410 BCE event is an extreme SEP event.
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12.
  • Reimer, Paula J., et al. (författare)
  • The IntCal20 Northern Hemisphere Radiocarbon Age Calibration Curve (0-55 cal kBP)
  • 2020
  • Ingår i: Radiocarbon. - 0033-8222. ; 62:4, s. 725-757
  • Tidskriftsartikel (refereegranskat)abstract
    • Radiocarbon (C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
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  • Cuneo, Bettina F., et al. (författare)
  • Mothers with long QT syndrome are at increased risk for fetal death : findings from a multicenter international study
  • 2020
  • Ingår i: American Journal of Obstetrics and Gynecology. - : MOSBY-ELSEVIER. - 0002-9378 .- 1097-6868. ; 222:3, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical data-bases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at <= 20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P = .036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.
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15.
  • Kaizer, Alexander M., et al. (författare)
  • Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
  • 2023
  • Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:11
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.CONCLUSION: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.
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16.
  • Schnieders, R, et al. (författare)
  • 1H, 13C and 15N chemical shift assignment of the stem-loop 5a from the 5'-UTR of SARS-CoV-2
  • 2021
  • Ingår i: Biomolecular NMR assignments. - : Springer Science and Business Media LLC. - 1874-270X .- 1874-2718. ; 15:1, s. 203-211
  • Tidskriftsartikel (refereegranskat)abstract
    • The SARS-CoV-2 (SCoV-2) virus is the causative agent of the ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to the genus of Betacoronaviruses. The 5′- and 3′-genomic ends of the 30 kb SCoV-2 genome are potential antiviral drug targets. Major parts of these sequences are highly conserved among Betacoronaviruses and contain cis-acting RNA elements that affect RNA translation and replication. The 31 nucleotide (nt) long highly conserved stem-loop 5a (SL5a) is located within the 5′-untranslated region (5′-UTR) important for viral replication. SL5a features a U-rich asymmetric bulge and is capped with a 5′-UUUCGU-3′ hexaloop, which is also found in stem-loop 5b (SL5b). We herein report the extensive 1H, 13C and 15N resonance assignment of SL5a as basis for in-depth structural studies by solution NMR spectroscopy.
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17.
  • Brehm, Nicolas, et al. (författare)
  • Tree-rings reveal two strong solar proton events in 7176 and 5259 BCE
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Sun sporadically produces eruptive events leading to intense fluxes of solar energetic particles (SEPs) that dramatically disrupt the near-Earth radiation environment. Such events have been directly studied for the last decades but little is known about the occurrence and magnitude of rare, extreme SEP events. Presently, a few events that produced measurable signals in cosmogenic radionuclides such as 14C, 10Be and 36Cl have been found. Analyzing annual 14C concentrations in tree-rings from Switzerland, Germany, Ireland, Russia, and the USA we discovered two spikes in atmospheric 14C occurring in 7176 and 5259 BCE. The ~2% increases of atmospheric 14C recorded for both events exceed all previously known 14C peaks but after correction for the geomagnetic field, they are comparable to the largest event of this type discovered so far at 775 CE. These strong events serve as accurate time markers for the synchronization with floating tree-ring and ice core records and provide critical information on the previous occurrence of extreme solar events which may threaten modern infrastructure.
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  • Fahrni, Simon M., et al. (författare)
  • Single-Year German oak and Californian Bristlecone Pine C Data at the Beginning of the Hallstatt Plateau from 856 BC to 626 BC
  • 2020
  • Ingår i: Radiocarbon. - 0033-8222. ; 62:4, s. 919-937
  • Tidskriftsartikel (refereegranskat)abstract
    • As part of the ongoing effort to improve the Northern Hemisphere radiocarbon (C) calibration curve, this study investigates the period of 856 BC to 626 BC (2805-2575 yr BP) with a total of 403 single-year C measurements. In this age range, IntCal13 was constructed largely from German and Irish oak as well as Californian bristlecone pine C dates, with most samples measured with a 10-yr resolution. The new data presented here is the first atmospheric C single-year record of the older end of the Hallstatt plateau based on an absolutely dated tree-ring chronology. The data helped reveal a major solar proton event (SPE) which caused a spike in the production rate of cosmogenic radionuclides around 2610/2609 BP. This production event is thought to have reached a magnitude similar to the 774/775 AD production event but has remained undetected due to averaging effects in the decadal calibration data. The record leading up to the 2610/2609 BP event reveals a 11-yr solar cycle with varying cyclicity. Features of the new data and the benefits of higher resolution calibration are discussed.
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  • Heaton, T. J., et al. (författare)
  • Radiocarbon : A key tracer for studying Earth’s dynamo, climate system, carbon cycle, and Sun
  • 2021
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6568
  • Forskningsöversikt (refereegranskat)abstract
    • Radiocarbon (14C), as a consequence of its production in the atmosphere and subsequent dispersal through the carbon cycle, is a key tracer for studying the Earth system. Knowledge of past 14C levels improves our understanding of climate processes, the Sun, the geodynamo, and the carbon cycle. Recently updated radiocarbon calibration curves (IntCal20, SHCal20, and Marine20) provide unprecedented accuracy in our estimates of 14C levels back to the limit of the 14C technique (~55,000 years ago). Such improved detail creates new opportunities to probe the Earth and climate system more reliably and at finer scale. We summarize the advances that have underpinned this revised set of radiocarbon calibration curves, survey the broad scientific landscape where additional detail on past 14C provides insight, and identify open challenges for the future.
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20.
  • Mukherjee, Koushik, et al. (författare)
  • Classical-linear-chain behavior from dipolar droplets to supersolids
  • 2023
  • Ingår i: Physical Review A (Atomic, Molecular and Optical Physics). - 2469-9926. ; 107:043319
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate the classicality of linear dipolar droplet arrays through a normal mode analysis of the dynamical properties in comparison to the supersolid regime. The vibrational patterns of isolated-droplet crystals that time-evolve after a small initial kick closely follow the properties of a linear droplet chain. For larger kick velocities, however, droplets may coalesce and separate again, showing distinct deviations from classicality. In the supersolid regime the normal modes are eliminated by a counterflow of mass between the droplets, signaled by a reduction of the center-of-mass motion. Our study effectively captures the vibrational patterns of isolated droplets in the presence of three-body loss and can be generalized to systems with a larger number of droplet arrays.
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21.
  • Nilsson Tengstrand, Mikael, et al. (författare)
  • Persistent Currents in Toroidal Dipolar Supersolids
  • 2021
  • Ingår i: Physical Review A. - 2469-9926. ; 103
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate the rotational properties of a dipolar Bose-Einstein condensate trapped in a toroidal geometry. Studying the ground states in the rotating frame and at fixed angular momenta, we observe that the condensate acts in distinctly different ways depending on whether it is in the superfluid or in the supersolid phase. We find that intriguingly, the toroidal dipolar condensate can support a supersolid persistent current which occurs at a local minimum in the ground state energy as a function of angular momentum, where the state has a vortex solution in the superfluid component of the condensate. The decay of this state is prevented by a barrier that in part consists of states where a fraction of the condensate mimics solid-body rotation in a direction opposite to that of the vortex. Furthermore, the rotating toroidal supersolid shows hysteretic behavior that is qualitatively different depending on the superfluid fraction of the condensate.
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22.
  • Önder, E., et al. (författare)
  • Frequency modulations due to domain dynamics in terahertz quantum cascade lasers
  • 2023
  • Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 133:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The light output of quantum cascade lasers is strongly affected by electric field-domain oscillations if the laser shows electrical instabilities. This can result in a substantial broadening of the emission spectrum, which is investigated here by detailed simulations for a terahertz device. We explain how the light pulsation is affected by electrical injection conditions and external capacitances. Experimental data confirm that the oscillation frequencies are not essentially affected by circuit conditions, while a large external capacitance produces almost non-observable oscillations due to stabilization of the circuit.
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