| 1. |
- Gaffney, K J, et al.
(författare)
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Observation of structural anisotropy and the onset of liquidlike motion during the nonthermal melting of InSb
- 2005
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 95:12
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Tidskriftsartikel (refereegranskat)abstract
- The melting dynamics of laser excited InSb have been studied with femtosecond x-ray diffraction. These measurements observe the delayed onset of diffusive atomic motion, signaling the appearance of liquidlike dynamics. They also demonstrate that the root-mean-squared displacement in the [111] direction increases faster than in the [110] direction after the first 500 fs. This structural anisotropy indicates that the initially generated fluid differs significantly from the equilibrium liquid.
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| 2. |
- Weigelt, G., et al.
(författare)
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VLTI-MATISSE chromatic aperture-synthesis imaging of eta Carinae's stellar wind across the Br alpha line Periastron passage observations in February 2020
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Eta Carinae is a highly eccentric, massive binary system (semimajor axis similar to 15.5 au) with powerful stellar winds and a phase-dependent wind-wind collision (WWC) zone. The primary star, eta Car A, is a luminous blue variable (LBV); the secondary, eta Car B, is a Wolf-Rayet or O star with a faster but less dense wind. Aperture-synthesis imaging allows us to study the mass loss from the enigmatic LBV eta Car. Understanding LBVs is a crucial step toward improving our knowledge about massive stars and their evolution. Aims. Our aim is to study the intensity distribution and kinematics of eta Car's WWC zone. Methods. Using the VLTI-MATISSE mid-infrared interferometry instrument, we perform Br alpha imaging of eta Car's distorted wind. Results. We present the first VLTI-MATISSE aperture-synthesis images of eta Car A's stellar windin several spectral channels distributed across the Br alpha 4.052 mu m line (spectral resolving power R similar to 960). Our observations were performed close to periastron passage in February 2020 (orbital phase similar to 14.0022). The reconstructed iso-velocity images show the dependence of the primary stellar wind on wavelength or line-of-sight (LOS) velocity with a spatial resolution of 6 mas (similar to 14 au). The radius of the faintest outer wind regions is similar to 26 mas (similar to 60 au). At several negative LOS velocities, the primary stellar wind is less extended to the northwest than in other directions. This asymmetry is most likely caused by the WWC. Therefore, we see both the velocity field of the undisturbed primary wind and the WWC cavity. In continuum spectral channels, the primary star wind is more compact than in line channels. A fit of the observed continuum visibilities with the visibilities of a stellar wind CMFGEN model (CMFGEN is an atmosphere code developed to model the spectra of a variety of objects) provides a full width at half maximum fit diameter of the primary stellar wind of 2.84 +/- 0.06 mas (6.54 +/- 0.14 au). We comparethe derived intensity distributions with the CMFGEN stellar wind model and hydrodynamic WWC models.
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| 3. |
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| 4. |
- Wade, G. A., et al.
(författare)
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The MiMeS survey of magnetism in massive stars : introduction and overview
- 2016
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 456:1, s. 2-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The MiMeS (Magnetism in Massive Stars) project is a large-scale, high-resolution, sensitive spectropolarimetric investigation of the magnetic properties of O- and early B-type stars. Initiated in 2008 and completed in 2013, the project was supported by three Large Program allocations, as well as various programmes initiated by independent principal investigators, and archival resources. Ultimately, over 4800 circularly polarized spectra of 560 O and B stars were collected with the instruments ESPaDOnS (Echelle SpectroPolarimetric Device for the Observation of Stars) at the Canada-France-Hawaii Telescope, Narval at the Telescope Bernard Lyot and HARPSpol at the European Southern Observatory La Silla 3.6 m telescope, making MiMeS by far the largest systematic investigation of massive star magnetism ever undertaken. In this paper, the first in a series reporting the general results of the survey, we introduce the scientific motivation and goals, describe the sample of targets, review the instrumentation and observational techniques used, explain the exposure time calculation designed to provide sensitivity to surface dipole fields above approximately 100 G, discuss the polarimetric performance, stability and uncertainty of the instrumentation, and summarize the previous and forthcoming publications.
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| 5. |
- Claesson, Elin, 1989, et al.
(författare)
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The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser
- 2020
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Ingår i: eLife. - 2050-084X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
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| 6. |
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| 7. |
- Damineli, Augusto, et al.
(författare)
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The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
- 2023
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
-
Tidskriftsartikel (refereegranskat)abstract
- Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
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| 8. |
- Gull, Theodore R., et al.
(författare)
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Eta Carinae : A Tale of Two Periastron Passages
- 2021
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 923:1, s. 102-102
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Tidskriftsartikel (refereegranskat)abstract
- Since 2002, the far-ultraviolet (FUV) flux (1150–1680 Å) of Eta Carinae, monitored by the Hubble Space Telescope/Space Telescope Imaging Spectrograph, has increased by an order of magnitude. This increase is attributed to partial dissipation of a line-of-sight (LOS) occulter that blocks the central core of the system. Across the 2020 February periastron passage, changes in the FUV emission show a stronger wavelength dependence than occurred across the 2003 July periastron passage. Across both periastron passages, most of the FUV spectrum dropped in flux then recovered a few months later. The 2020 periastron passage included enhancements of FUV flux in narrow spectral intervals near periastron followed by a transient absorption and recovery to pre-periastron flux levels. The drop in flux is due to increased absorption by singly ionized species as the secondary star plunges deep into the wind of the primary star, which blocks the companion's ionizing radiation. The enhanced FUV emission is caused by the companion's wind-blown cavity briefly opening a window to deeper layers of the primary star. This is the first time transient brightening has been seen in the FUV comparable to transients previously seen at longer wavelengths. Changes in resonance line-velocity profiles hint that the dissipating occulter is associated with material in LOS moving at −100 to −300 km s−1, similar in velocity of structures previously associated with the 1890s lesser eruption
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| 9. |
- Gull, Theodore R., et al.
(författare)
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Eta Carinae : An Evolving View of the Central Binary, Its Interacting Winds and Its Foreground Ejecta
- 2022
-
Ingår i: Astrophysical Journal. - : IOP Publishing Ltd. - 0004-637X .- 1538-4357. ; 933:2, s. 1-28
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Tidskriftsartikel (refereegranskat)abstract
- FUV spectra of eta Car, recorded across two decades with HST/STIS, document multiple changes in resonant lines caused by dissipating extinction in our line of sight. The FUV flux has increased nearly tenfold, which has led to increased ionization of the multiple shells within the Homunculus and photodestruction of H-2. Comparison of observed resonant line profiles with CMFGEN model profiles allows separation of wind-wind collision and shell absorptions from the primary wind P Cygni profiles. The dissipating occulter preferentially obscured the central binary and interacting winds relative to the very extended primary wind. We are now able to monitor changes in the colliding winds with orbital phase. High-velocity transient absorptions occurred across the most recent periastron passage, indicating acceleration of the primary wind by the secondary wind, which leads to a downstream, high-velocity bow shock that is newly generated every orbital period. There is no evidence of changes in the properties of the binary winds.
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| 10. |
- Gull, Theodore R., et al.
(författare)
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Eta Carinae - The Dissipating Occulter Is an Extended Structure
- 2023
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954:1
-
Tidskriftsartikel (refereegranskat)abstract
- Previous Hubble Space Telescope (HST)/Space Telescope Imaging Spectrograph (STIS) longslit observations of Eta Carinae (η Car) identified numerous absorption features in both the stellar spectrum, and in the adjacent nebular spectra, along our line of sight (LOS). The absorption features became temporarily stronger when the ionizing far-ultraviolet radiation field was reduced by the periastron passage of the secondary star. Subsequently, dissipation of a dusty structure in our LOS has led to a long-term increase in the apparent brightness of η Car, an increase in the ionizing ultraviolet (UV) radiation, and the disappearance of absorption from multiple velocity-separated shells extending across the foreground Homunculus lobe. We use HST/STIS spectro-images, coupled with published infrared and radio observations, to locate this intervening dusty structure. The velocity and spatial information indicate the occulter is ≈1000 au in front of η Car. The Homunculus is a transient structure composed of dusty, partially ionized ejecta that eventually will disappear due to the relentless rain of ionizing radiation and wind from the current binary system along with dissipation and mixing with the interstellar medium. This evolving complex continues to provide an astrophysical laboratory that changes on human timescales.
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| 11. |
- Pablo, H., et al.
(författare)
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epsilon Lupi : measuring the heartbeat of a doubly magnetic massive binary with BRITE Constellation
- 2019
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 488:1, s. 64-77
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Tidskriftsartikel (refereegranskat)abstract
- epsilon Lupi A is a binary system consisting of two main-sequence early B-type stars Aa and Ab in a short period, moderately eccentric orbit. The close binary pair is the only doubly magnetic massive binary currently known. Using photometric data from the BRITE Constellation we identify a modest heartbeat variation. Combining the photometry with radial velocities of both components we determine a full orbital solution including empirical masses and radii. These results are compared with stellar evolution models as well as interferometry and the differences discussed. We also find additional photometric variability at several frequencies, finding it unlikely these frequencies can be caused by tidally excited oscillations. We do, however, determine that these signals are consistent with gravity mode pulsations typical for slowly pulsating B stars. Finally we discuss how the evolution of this system will be affected by magnetism, determining that tidal interactions will still be dominant.
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| 12. |
- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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| 13. |
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| 14. |
- Edlund, Petra, et al.
(författare)
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The room temperature crystal structure of a bacterial phytochrome determined by serial femtosecond crystallography
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 angstrom resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 angstrom resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
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| 15. |
- Gabrysch, Markus, et al.
(författare)
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Formation of secondary electron cascades in single-crystalline plasma-deposited diamond upon exposure to femtosecond x-ray pulses
- 2008
-
Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 103:6
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Tidskriftsartikel (refereegranskat)abstract
- Secondary electron cascades were measured in high purity single-crystalline chemical vapor deposition (CVD) diamond, following exposure to ultrashort hard x-ray pulses (140 fs full width at half maximum, 8.9 keV energy) from the Sub-Picosecond Pulse Source at the Stanford Linear Accelerator Center. We report measurements of the pair creation energy and of drift mobility of carriers in two CVD diamond crystals. This was done for the first time using femtosecond x-ray excitation. Values for the average pair creation energy were found to be 12.17 +/- 0.57 and 11.81 +/- 0.59 eV for the two crystals, respectively. These values are in good agreement with recent theoretical predictions. The average drift mobility of carriers, obtained by the best fit to device simulations, was mu(h)= 2750 cm(2)/V s for holes and was mu(e)= 2760 cm(2) / V s for electrons. These mobility values represent lower bounds for charge mobilities due to possible polarization of the samples. The results demonstrate outstanding electric properties and the enormous potential of diamond in ultrafast x-ray detectors.
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| 16. |
- Hareter, M., et al.
(författare)
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MOST discovers a multimode delta Scuti star in a triple system : HD 61199
- 2008
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 492:1, s. 185-195
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Tidskriftsartikel (refereegranskat)abstract
- Context. A field star, HD61199 (V approximate to 8), simultaneously observed with Procyon by the MOST (Microvariability & Oscillations of STars) satellite in continuous runs of 34, 17, and 34 days in 2004, 2005, and 2007, was found to pulsate in 11 frequencies in the delta Scuti range with amplitudes from 1.7 down to 0.09 mmag. The photometry also showed variations with a period of about four days. To investigate the nature of the longer period, 45 days of time-resolved spectroscopy was obtained at the Thuringer Landessternwarte Tautenburg in 2004. The radial velocity measurements indicate that HD61199 is a triple system. Aims. A delta Scuti pulsator with a rich eigenspectrum in a multiple system is promising for asteroseismology. Our objectives were to identify which of the stars in the system is the delta Scuti variable and to obtain the orbital elements of the system and the fundamental parameters of the individual components, which are constrained by the pulsation frequencies of the delta Scuti star.Methods. Classical Fourier techniques and least-squares multi-sinusoidal fits were applied to the MOST photometry to identify the pulsation frequencies. The groundbased spectroscopy was analysed with least-squares-deconvolution (LSD) techniques, and the orbital elements derived with the KOREL and ORBITX routines. Asteroseismic models were also generated. Results. The photometric and spectroscopic data are compatible with a triple system consisting of a close binary with an orbital period of 3.57 days and a d Scuti companion (HD61199 A) as the most luminous component. The d Scuti star is a rapid rotator with about v sin i = 130 km s(-1) and an upper mass limit of about 2.1 M-circle dot. For the close binary components, we find they are of nearly equal mass, with lower mass limits of about 0.7 M-circle dot. Comparisons to synthetic spectra indicate these stars have a late-F spectral type. The observed oscillation frequencies are compared to pulsation models to further constrain the evolutionary state and mass of HD61199 A. The orbit frequency of the close binary corresponds to the difference of the two d Scuti frequencies with the highest amplitudes a coincidence that is remarkable, but not explained.
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| 17. |
- Hart, Traver, et al.
(författare)
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High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities
- 2015
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 163:6
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Tidskriftsartikel (refereegranskat)abstract
- The ability to perturb genes in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. To extend the catalog of human core and context-dependent fitness genes, we have developed a high-complexity second-generation genome-scale CRISPR-Cas9 gRNA library and applied it to fitness screens in five human cell lines. Using an improved Bayesian analytical approach, we consistently discover 5-fold more fitness genes than were previously observed. We present a list of 1,580 human core fitness genes and describe their general properties. Moreover, we demonstrate that context-dependent fitness genes accurately recapitulate pathway-specific genetic vulnerabilities induced by known oncogenes and reveal cell-type-specific dependencies for specific receptor tyrosine kinases, even in oncogenic KRAS backgrounds. Thus, rigorous identification of human cell line fitness genes using a high-complexity CRISPR-Cas9 library affords a high-resolution view of the genetic vulnerabilities of a cell.
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| 18. |
- Haughney, John, et al.
(författare)
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Achieving asthma control in practice: Understanding the reasons for poor control
- 2008
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 102:12, s. 1681-1693
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Forskningsöversikt (refereegranskat)abstract
- Achieving asthma control remains an elusive goat for the majority of patients worldwide. Ensuring a correct diagnosis of asthma is the first step in assessing poor symptom control; this requires returning to the basics of history taking and physical examination, in conjunction with lung function measurement when appropriate. A number of factors may contribute to suboptimal asthma control. Concomitant rhinitis, a common co-pathology and contributor to poor control, can often be identified by asking a simple question. Smoking too has been identified as a cause of poor asthma control. Practical barriers such as poor inhaler technique must be addressed. An appreciation of patients' views and concerns about maintenance asthma therapy can help guide discussion to address perceptual barriers to taking maintenance therapy (doubts about personal necessity and concerns about potential adverse effects). Further study into, and a greater consideration of, factors and patient characteristics that could predict individual responses to asthma therapies are needed. Finally, more clinical trials that enrol patient populations reflecting the real world diversity of patients seen in clinical. practice, including wide age ranges, presence of comorbidities, current smoking, and differing ethnic origins, will contribute to better individual patient management. (C) 2008 Elsevier Ltd. All rights reserved.
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| 19. |
- Horger, B A, et al.
(författare)
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Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons
- 1998
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 18:13, s. 4929-4937
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Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
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| 20. |
- Karikari, Thomas, et al.
(författare)
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The C291R Tau Variant Forms Different Types of Protofibrils
- 2020
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Ingår i: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the MAPT gene can lead to disease-associated variants of tau. However, the pathological mechanisms behind these genetic tauopathies are poorly understood. Here, we characterized the aggregation stages and conformational changes of tau C291R, a recently described MAPT mutation with potential pathogenic functions. The C291R variant of the tau four-repeat domain (tau-K18; a functional fragment with increased aggregation propensity compared with the full-length protein), aggregated into a mix of granular oligomers, amorphous and annular pore-like aggregates, in native-state and heparin-treated reactions as observed using atomic force microscopy (AFM) and negative-stained electron microscopy. On extended incubation in the native-state, tau-K18 C291R oligomers, unlike wild type (WT) tau-K18, aggregated to form protofibrils of four different phenotypes: (1) spherical annular; (2) spherical annular encapsulating granular oligomers; (3) ring-like annular but non-spherical; and (4) linear protofibrils. The ring-like tau-K18 C291R aggregates shared key properties of annular protofibrils previously described for other amyloidogenic proteins, in addition to two unique features: irregular/non-spherical-shaped annular protofibrils, and spherical protofibrils encapsulating granular oligomers. Tau-K18 C291R monomers had a circular dichroism (CD) peak at similar to 210 nm compared with similar to 199 nm for tau-K18 WT. These data suggest mutation-enhanced beta-sheet propensity. Together, we describe the characterization of tau-K18 C291R, the first genetic mutation substituting a cysteine residue. The aggregation mechanism of tau-K18 C291R appears to involve beta-sheet-rich granular oligomers which rearrange to form unique protofibrillar structures.
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| 21. |
- Norris, Shane A., et al.
(författare)
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Understanding and acting on the developmental origins of health and disease in Africa would improve health across generations
- 2017
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Ingår i: Global Health Action. - : TAYLOR & FRANCIS LTD. - 1654-9716 .- 1654-9880. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Data from many high- and low- or middle-income countries have linked exposures during key developmental periods (in particular pregnancy and infancy) to later health and disease. Africa faces substantial challenges with persisting infectious disease and now burgeoning non-communicable disease. This paper opens the debate to the value of strengthening the developmental origins of health and disease (DOHaD) research focus in Africa to tackle critical public health challenges across the life-course. We argue that the application of DOHaD science in Africa to advance life-course prevention programmes can aid the achievement of the Sustainable Development Goals, and assist in improving health across generations. To increase DOHaD research and its application in Africa, we need to mobilise multisectoral partners, utilise existing data and expertise on the continent, and foster a new generation of young African scientists engrossed in DOHaD.
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| 22. |
- Pickett, Connor S., et al.
(författare)
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Changes in the Na D-1 Absorption Components of eta Carinae Provide Clues on the Location of the Dissipating Central Occulter
- 2022
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Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 937:2
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Tidskriftsartikel (refereegranskat)abstract
- The Na D absorption doublet in the spectrum of eta Carinae is complex, with multiple absorption features associated with the Great Eruption (1840s), the Lesser Eruption (1890s), and the interstellar clouds. The velocity profile is further complicated by the P Cygni profile originating in the system's stellar winds and blending with the He i lambda 5876 profile. The Na D profile contains a multitude of absorption components, including those at velocities of -145 km s(-1), -168 km s(-1), and +87 km s(-1), which we concentrate on in this analysis. Ground-based spectra recorded from 2008 to 2021 show significant variability of the -145 km s(-1) absorption throughout long-term observations. In the high-ionization phases of eta Carinae prior to the 2020 periastron passage, this feature disappeared completely but briefly reappeared across the 2020 periastron, along with a second absorption at -168 km s(-1). Over the past few decades, eta Carinae has been gradually brightening, which is shown to be caused by a dissipating occulter. The decreasing absorption of the -145 km s(-1) component, coupled with similar trends seen in absorptions of ultraviolet resonant lines, indicate that this central occulter was possibly a large clump associated with the Little Homunculus or another clump between the Little Homunculus and the star. We also report on a foreground absorption component at +87 km s(-1). Comparison of Na D absorption in the spectra of nearby systems demonstrates that this redshifted component likely originates in an extended foreground structure consistent with a previous ultraviolet spectral survey in the Carina Nebula.
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| 23. |
- Qazi, Maleeha A, et al.
(författare)
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Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma.
- 2018
-
Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:17, s. 5023-5037
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to GBM therapy. In this study, we identify several EphRs that mark a therapeutically targetable GSC population in treatment-refractory, recurrent GBM (rGBM). Using a highly specific EphR antibody panel and CyTOF (cytometry by time-of-flight), we characterized the expression of all 14 EphR in primary and recurrent patient-derived GSCs to identify putative rGBM-specific EphR. EPHA2 and EPHA3 coexpression marked a highly tumorigenic cell population in rGBM that was enriched in GSC marker expression. Knockdown of EPHA2 and EPHA3 together led to increased expression of differentiation marker GFAP and blocked clonogenic and tumorigenic potential, promoting significantly higher survival in vivo Treatment of rGBM with a bispecific antibody against EPHA2/A3 reduced clonogenicity in vitro and tumorigenic potential of xenografted recurrent GBM in vivo via downregulation of AKT and ERK and increased cellular differentiation. In conclusion, we show that EPHA2 and EPHA3 together mark a GSC population in rGBM and that strategic cotargeting of EPHA2 and EPHA3 presents a novel and rational therapeutic approach for rGBM.Significance: Treatment of rGBM with a novel bispecific antibody against EPHA2 and EPHA3 reduces tumor burden, paving the way for the development of therapeutic approaches against biologically relevant targets in rGBM. Cancer Res; 78(17); 5023-37.
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| 24. |
- Weiss, W. W., et al.
(författare)
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New BRITE-Constellation observations of the roAp star α Cir⋆
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
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Tidskriftsartikel (refereegranskat)abstract
- Context. Chemically peculiar (CP) stars with a measurable magnetic field comprise the group of mCP stars. The pulsating members define the subgroup of rapidly oscillating Ap (roAp) stars, of which alpha Cir is the brightest member. Hence, alpha Cir allows the application of challenging techniques, such as interferometry, very high temporal and spectral resolution photometry, and spectroscopy in a wide wavelength range, that have the potential to provide unique information about the structure and evolution of a star.Aims. Based on new photometry from BRITE-Constellation, obtained with blue and red filters, and on photometry from WIRE, SMEI, and TESS we attempt to determine the surface spot structure of alpha Cir and investigate pulsation frequencies.Methods. We used photometric surface imaging and frequency analyses and Bayesian techniques in order to quantitatively compare the probability of different models.Results. BRITE-Constellation photometry obtained from 2014 to 2016 is put in the context of space photometry obtained by WIRE, SMEI, and TESS. This provides improvements in the determination of the rotation period and surface features (three spots detected and a fourth one indicated). The main pulsation frequencies indicate two consecutive radial modes and one intermediate dipolar mode. Advantages and problems of the applied Bayesian technique are discussed.
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| 25. |
- Zwintz, K., et al.
(författare)
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beta Cas : The first ffi Scuti star with a dynamo magnetic field
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 643
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Tidskriftsartikel (refereegranskat)abstract
- Context. F-type stars are characterised by several physical processes such as different pulsation mechanisms, rotation, convection, diffusion, and magnetic fields. The rapidly rotating delta Scuti star beta Cas can be considered as a benchmark star to study the interaction of several of these effects.Aims. We investigate the pulsational and magnetic field properties of beta Cas. We also determine the star's apparent fundamental parameters and chemical abundances.Methods. Based on photometric time series obtained from three different space missions (BRITE-Constellation, SMEI, and TESS), we conduct a frequency analysis and investigate the stability of the pulsation amplitudes over four years of observations. We investigate the presence of a magnetic field and its properties using spectropolarimetric observations taken with the Narval instrument by applying the least-squares deconvolution and Zeeman-Doppler imaging techniques.Results. The star beta Cas shows only three independent p-mode frequencies down to the few ppm-level; its highest amplitude frequency is suggested to be an n=3, l=2, m=0 mode. Its magnetic field structure is quite complex and almost certainly of a dynamo origin. The atmosphere of beta Cas is slightly deficient in iron peak elements and slightly overabundant in C, O, and heavier elements.Conclusions. Atypically for delta Scuti stars, we can only detect three pulsation modes down to exceptionally low noise levels for beta Cas. The star is also one of very few delta Scuti pulsators known to date to show a measurable magnetic field and the first delta Scuti star with a dynamo magnetic field. These characteristics make beta Cas an interesting target for future studies of dynamo processes in the thin convective envelopes of F-type stars, the transition region between fossil and dynamo fields, and the interaction between pulsations and magnetic field.
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