The bright supergiant Betelgeuse (Alpha Orionis, HD 39801) experienced a visual dimming during 2019 December and the first quarter of 2020, reaching an historic minimum 2020 February 7-13. During ...2019 September-November, prior to the optical dimming event, the photosphere was expanding. At the same time, spatially resolved ultraviolet spectra using the Hubble Space Telescope/Space Telescope Imaging Spectrograph revealed a substantial increase in the ultraviolet spectrum and Mg ii line emission from the chromosphere over the southern hemisphere of the star. Moreover, the temperature and electron density inferred from the spectrum and C ii diagnostics also increased in this hemisphere. These changes happened prior to the Great Dimming Event. Variations in the Mg ii k-line profiles suggest material moved outwards in response to the passage of a pulse or acoustic shock from 2019 September through November. It appears that this extraordinary outflow of material from the star, likely initiated by convective photospheric elements, was enhanced by the coincidence with the outward motions in this phase of the ∼400 day pulsation cycle. These ultraviolet observations appear to provide the connecting link between the known large convective cells in the photosphere and the mass ejection event that cooled to form the dust cloud in the southern hemisphere imaged in 2019 December, and led to the exceptional optical dimming of Betelgeuse in 2020 February.
Abstract
The luteinizing hormone receptor (LHCGR) is expressed at low levels in mural granulosa cells and cumulus cells of antral follicles and is induced dramatically in granulosa cells but not in ...cumulus cells by follicle-stimulating hormone (FSH). Therefore, we hypothesized that FSH not only activates transcription factors controlling Lhcgr expression but also alters other events to permit and enhance Lhcgr expression in granulosa cells but not in cumulus cells. In granulosa cells, the level of DNA methylation in the Lhcgr promoter region was significantly decreased by equine chorionic gonadotropin (eCG) in vivo. However, in cumulus cells, hypermethylation of the Lhcgr promoter remained after eCG stimulation. eCG induced estrogen production from testosterone (T) and retinoic acid (RA) synthesis in granulosa cells. When either T or RA in the presence or absence of FSH was added to granulosa cell cultures, the combined treatment with FSH and RA induced demethylation of Lhcgr-promoter region and Lhcgr expression. FSH-dependent RA synthesis was negatively regulated by coculture of granulosa cells with denuded oocytes, suggesting that oocyte-secreted factors downregulate RA production in cumulus cells where Lhcgr expression was not induced. Strikingly, treatment of cultured cumulus-oocyte complexes with a SMAD inhibitor, SB431542, significantly induced RA production, demethylation of Lhcgr-promoter region, and Lhcgr expression in cumulus cells. These results indicate the demethylation of the Lhcgr-promoter region is mediated, at least in part, by RA synthesis and is a key mechanism regulating the cell type–specific differentiation during follicular development.
Oocytes negatively regulate retinoic acid synthesis in preovulatory follicles, which affects the expression of Lhcgr in follicular somatic cells via a DNA-demethylation–dependent mechanism.
Rhythmic events in female reproductive physiology, including ovulation, are tightly controlled by the circadian timing system. The molecular clock, a feedback loop oscillator of clock gene ...transcription factors, dictates rhythms of gene expression in the hypothalamo-pituitary-ovarian axis. Circadian disruption due to environmental factors (eg, shift work) or genetic manipulation of the clock has negative impacts on fertility. Although the central pacemaker in the suprachiasmatic nucleus classically regulates the timing of ovulation, we have shown that this rhythm also depends on phasic sensitivity to LH. We hypothesized that this rhythm relies on clock function in a specific cellular compartment of the ovarian follicle. To test this hypothesis we generated mice with deletion of the Bmal1 locus in ovarian granulosa cells (GCs) (Granulosa Cell Bmal1 KO; GCKO) or theca cells (TCs) (Theca Cell Bmal1 KO; TCKO). Reproductive cycles, preovulatory LH secretion, ovarian morphology and behavior were not grossly altered in GCKO or TCKO mice. We detected phasic sensitivity to LH in wild-type littermate control (LC) and GCKO mice but not TCKO mice. This decline in sensitivity to LH is coincident with impaired fertility and altered patterns of LH receptor (Lhcgr) mRNA abundance in the ovary of TCKO mice. These data suggest that the TC is a pacemaker that contributes to the timing and amplitude of ovulation by modulating phasic sensitivity to LH. The TC clock may play a critical role in circadian disruption-mediated reproductive pathology and could be a target for chronobiotic management of infertility due to environmental circadian disruption and/or hormone-dependent reprogramming in women.
The application of synthetic glycopolymers to anti-adhesive therapies has so far been limited by their lack of lectin specificity. Here we employ a macromolecular engineering approach to mimic glycan ...architecture. A new, 3-step tandem post-polymerisation methodology was developed which afforded precise control over both chain length and carbohydrate (galactose)-polymer backbone linker distance. This route also allowed a secondary binding (branched) motif to be introduced onto the linker, increasing specificity and affinity towards bacterial toxins without the need for extensive carbohydrate or organic chemistry. Sequential variation of this motif was found to dramatically alter both the affinity and the specificity of the glycopolymers towards two lectins, CTx and PNA, by up to 20-fold either viadirect binding, or increased steric constraints. Using this method, a glycopolymer that showed increased specificity towards CTx was identified.
A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Because the signaling molecules RAS and ...ERK1/2 (extracellular signal-regulated kinases 1 and 2) are activated by an LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBPβ (CCAAT/Enhancer-binding protein-β) is a critical downstream mediator of ERK1/2 activation. Thus, ERK1/2 and C/EBPβ constitute an in vivo LH-regulated signaling pathway that controls ovulation- and luteinization-related events.
Upconversion (UC) is a promising option to enhance the efficiency of solar cells by conversion of sub-bandgap infrared photons to higher energy photons that can be utilized by the solar cell. The UC ...quantum yield is a key parameter for a successful application. Here the UC luminescence properties of Er3+-doped Gd2O2S are investigated by means of luminescence spectroscopy, quantum yield measurements, and excited state dynamics experiments. Excitation into the maximum of the 4I15/2 → 4I13/2 Er3+ absorption band around 1500 nm induces very efficient UC emission from different Er3+ excited states with energies above the silicon bandgap, in particular, the emission originating from the 4I11/2 state around 1000 nm. Concentration dependent studies reveal that the highest UC quantum yield is realized for a 10% Er3+-doping concentration. The UC luminescence is compared to the well-known Er3+-doped β-NaYF4 UC material for which the highest UC quantum yield has been reported for 25% Er3+. The UC internal quantum yields were measured in this work for Gd2O2S: 10%Er3+ and β-NaYF4: 25%Er3+ to be 12 ± 1% and 8.9 ± 0.7%, respectively, under monochromatic excitation around 1500 nm at a power of 700 W/m2. The UC quantum yield reported here for Gd2O2S: 10%Er3+ is the highest value achieved so far under monochromatic excitation into the 4I13/2 Er3+ level. Power dependence and lifetime measurements were performed to understand the mechanisms responsible for the efficient UC luminescence. We show that the main process yielding 4I11/2 UC emission is energy transfer UC.
The molecular bridges that link the LH surge with functional changes in cumulus cells that possess few LH receptors are being unraveled. Herein we document that epidermal growth factor (EGF)-like ...factors amphiregulin (Areg), epiregulin (Ereg), and betacellulin (Btc) are induced in cumulus oocyte complexes (COCs) by autocrine and paracrine mechanisms that involve the actions of prostaglandins (PGs) and progesterone receptor (PGR). Areg and Ereg mRNA and protein levels were reduced significantly in COCs and ovaries collected from prostaglandin synthase 2 (Ptgs2) null mice and Pgr null (PRKO) mice at 4 h and 8 h after human chorionic gonadotropin, respectively. In cultured COCs, FSH/forskolin induced Areg mRNA within 0.5 h that peaked at 4 h, a process blocked by inhibitors of p38MAPK (SB203580), MAPK kinase (MEK) 1 (PD98059), and PTGS2 (NS398) but not protein kinase A (PKA) (KT5720). Conversely, AREG but not FSH induced Ptsg2 mRNA at 0.5 h with peak expression of Ptgs2 and Areg mRNAs at 4 h, processes blocked by the EGF receptor tyrosine kinase inhibitor AG1478 (AG), PD98059, and NS398. PGE2 reversed the inhibitory effects of AG on AREG-induced expression of Areg but not Ptgs2, placing Ptgs2 downstream of EGF-R signaling. Phorbol 12-myristate 13-acetate (PMA) and adenovirally expressed PGRA synergistically induced Areg mRNA in granulosa cells. In COCs, AREG not only induced genes that impact matrix formation but also genes involved in steroidogenesis (StAR, Cyp11a1) and immune cell-like functions (Pdcd1, Runx1, Cd52). Collectively, FSH-mediated induction of Areg mRNA via p38MAPK precedes AREG induction of Ptgs2 mRNA via ERK1/2. PGs acting via PTGER2 in cumulus cells provide a secondary, autocrine pathway to regulate expression of Areg in COCs showing critical functional links between G protein-coupled receptor and growth factor receptor pathways in ovulating follicles.
Light Detection and Ranging (LiDAR) provides high resolution horizontal and vertical spatial point cloud data, and is increasingly being used in a number of applications and disciplines, which have ...concentrated on the exploit and manipulation of the data using mainly its three dimensional nature. LiDAR information potential is made even greater though, with its consideration of intensity.
Elevation and intensity airborne LiDAR data are used in this study in order to classify forest and ground types quickly and efficiently without the need for manipulating multispectral image files, using a supervised object-orientated approach. LiDAR has the advantage of being able to create elevation surfaces that are in 3D, while also having information on LiDAR intensity values, thus it is a spatial and spectral segmentation tool. This classification method also uses point distribution frequency criteria to differentiate between land cover types. Classifications were performed using two methods, one that included the influence of the ground in heavily vegetated areas, and the other which eliminated the ground points before classification. The classification of three meanders of the Garonne and Allier rivers in France has demonstrated overall classification accuracies of 95% and 94% for the methods including and excluding the ground influence respectively. Five types of riparian forest were classified with accuracies between 66 and 98%. These forest types included planted and natural forest stands of different ages. Classifications of short vegetation and bare earth also produced high accuracies averaging above 90%.
Summary
Alemtuzumab, a humanized anti‐CD52 monoclonal antibody, is approved for treatment of relapsing multiple sclerosis (MS). In the Phase II/III trials, patients received 12 or 24 mg/day of ...alemtuzumab in two treatment courses (5 days for course 1 and 3 days for course 2), 12 months apart. Serum concentrations of alemtuzumab peaked on the last day of dosing in each course and mostly fell below the limit of quantitation by day 30. Alemtuzumab rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days. Lymphocytes repopulated over time, with B cell recovery usually complete within 6 months. T lymphocytes recovered more slowly and generally did not return to baseline by 12 months post‐treatment. Approximately 40 and 80% of patients had total lymphocyte counts, reaching the lower limit of normal by 6 and 12 months after each course, respectively. The clearance of alemtuzumab is dependent on circulating lymphocyte count. A majority of treated patients tested positive for anti‐alemtuzumab antibodies, including inhibitory antibodies, during the 2‐year studies, and a higher proportion of patients tested positive in course 2 than in course 1. The presence of anti‐alemtuzumab antibody appeared to be associated with slower clearance of alemtuzumab from the circulation but had no impact on the pharmacodynamics. No effects of age, race or gender on the pharmacokinetics or pharmacodynamics were observed. Together, the pharmacokinetics, pharmacodynamics and immunogenicity results support the continued development and use of alemtuzumab for the treatment of MS, and probably explain its sustained effects beyond the dosing interval.
Alemtuzumab, a humanized anti‐CD52 monoclonal antibody, given to multiple sclerosis (MS) patients at 12 or 24 mg/day in two treatment courses (5 days for course 1 and 3 days for course 2), 12 months apart, rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days. Lymphocytes repopulated over time, with B cell recovery usually complete within 6 months. T lymphocytes recovered more slowly and generally did not return to baseline by 12 months post‐treatment. The pharmacokinetics, pharmacodynamics and immunogenicity of alemtuzumab in MS were discussed.
Short-wave infrared (SWIR) fluorescence could become the new gold standard in optical imaging for biomedical applications due to important advantages such as lack of autofluorescence, weak photon ...absorption by blood and tissues, and reduced photon scattering coefficient. Therefore, contrary to the visible and NIR regions, tissues become translucent in the SWIR region. Nevertheless, the lack of bright and biocompatible probes is a key challenge that must be overcome to unlock the full potential of SWIR fluorescence. Although rare-earth-based core-shell nanocrystals appeared as promising SWIR probes, they suffer from limited photoluminescence quantum yield (PLQY). The lack of control over the atomic scale organization of such complex materials is one of the main barriers limiting their optical performance. Here, the growth of either homogeneous (α-NaYF
) or heterogeneous (CaF
) shell domains on optically-active α-NaYF
:Yb:Er (with and without Ce
co-doping) core nanocrystals is reported. The atomic scale organization can be controlled by preventing cation intermixing only in heterogeneous core-shell nanocrystals with a dramatic impact on the PLQY. The latter reached 50% at 60 mW/cm
; one of the highest reported PLQY values for sub-15 nm nanocrystals. The most efficient nanocrystals were utilized for in vivo imaging above 1450 nm.
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