ABSTRACT
HATS-18 b is a transiting planet with a large mass and a short orbital period, and is one of the best candidates for the detection of orbital decay induced by tidal effects. We present ...extensive photometry of HATS-18 from which we measure 27 times of mid-transit. Two further transit times were measured from data from the Transiting Exoplanet Survey Satellite (TESS) and three more taken from the literature. The transit timings were fitted with linear and quadratic ephemerides and an upper limit on orbital decay was determined. This corresponds to a lower limit on the modified stellar tidal quality factor of $Q_\star ^{\, \prime } \gt 10^{5.11 \pm 0.04}$. This is at the cusp of constraining the presence of enhanced tidal dissipation due to internal gravity waves. We also refine the measured physical properties of the HATS-18 system, place upper limits on the masses of third bodies, and compare the relative performance of TESS and the 1.54 m Danish Telescope in measuring transit times for this system.
Summary Background & aims Inflammation is catabolic and causes muscle loss. It is unknown if amino acid supplementation reverses these effects during the acute phase of inflammation. The aim was to ...test whether amino acid supplementation counteracts endotoxin-induced catabolism. Methods Eight young, healthy, lean males were investigated three times in randomized order: (i) normal conditions (Placebo), (ii) endotoxemia (LPS), and (iii) endotoxemia with amino acid supplementation (LPS + A). Protein kinetics were determined using phenylalanine, tyrosine, and urea tracers. Each study day consisted of a four-hour non-insulin stimulated period and a two-hour hyperinsulinemic euglycemic clamp period. Muscle biopsies were collected once each period. Results Endotoxin administration created a significant inflammatory response (cytokines, hormones, and vital parameters) without significant differences between LPS and LPS + A. Whole body protein breakdown was elevated during LPS compared with Placebo and LPS + A (p < 0.05). Whole body protein synthesis was higher during LPS + A than both Placebo and LPS (p < 0.003). Furthermore, protein synthesis was higher during LPS than during Placebo (p < 0.02). Net muscle phenylalanine release was markedly decreased during LPS + A (p < 0.004), even though muscle protein synthesis and breakdown rates did not differ significantly between interventions. LPS + A increased mammalian target of rapamycin (mTOR) phosphorylation (p < 0.05) and eukaryotic translation factor 4E-binding protein 1 (4EBP1) phosphorylation (p = 0.007) without activating AMPK or affecting insulin signaling through Akt. During insulin stimulation net muscle phenylalanine release and protein degradation were further reduced. Conclusions Amino acid supplementation in the acute phase of inflammation reduces whole body and muscle protein loss, and this effect is associated with activation of mTOR and downstream signaling to protein synthesis through mTORC1, suggesting a therapeutic role for intravenous amino acids in inflammatory states. Clinical trial registry : The Central Denmark Region Ethics Commitee (1-10-71-410-12) www.clinicaltrials.gov (identification number NCT01705782 ).
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Aims. Our aim in this paper is to refine the orbital and physical parameters of the HATS-2 planetary system and study transit timing variations and atmospheric composition thanks to transit ...observations that span more than 10 yr and that were collected using different instruments and pass-band filters. We also investigate the orbital alignment of the system by studying the anomalies in the transit light curves induced by starspots on the photosphere of the parent star. Methods. We analysed new transit events from both ground-based telescopes and NASA’s TESS mission. Anomalies were detected in most of the light curves and modelled as starspots occulted by the planet during transit events. We fitted the clean and symmetric light curves with the JKTEBOP code and those affected by anomalies with the PRISM+GEMC codes to simultaneously model the photometric parameters of the transits and the position, size, and contrast of each starspot. Results. We found consistency between the values we found for the physical and orbital parameters and those from the discovery paper and ATLAS9 stellar atmospherical models. We identified different sets of consecutive starspot-crossing events that temporally occurred in less than five days. Under the hypothesis that we are dealing with the same starspots, occulted twice by the planet during two consecutive transits, we estimated the rotational period of the parent star and, in turn the projected and the true orbital obliquity of the planet. We find that the system is well aligned. We identified the possible presence of transit timing variations in the system, which can be caused by tidal orbital decay, and we derived a low-resolution transmission spectrum.
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4.
Six Outbursts of Comet 46P/Wirtanen Kelley, Michael S. P.; Farnham, Tony L.; Li, Jian-Yang ...
The planetary science journal,
08/2021, Volume:
2, Issue:
4
Journal Article
Peer reviewed
Open access
Abstract
Cometary activity is a manifestation of sublimation-driven processes at the surface of nuclei. However, cometary outbursts may arise from other processes that are not necessarily driven by ...volatiles. In order to fully understand nuclear surfaces and their evolution, we must identify the causes of cometary outbursts. In that context, we present a study of mini-outbursts of comet 46P/Wirtanen. Six events are found in our long-term lightcurve of the comet around its perihelion passage in 2018. The apparent strengths range from −0.2 to −1.6 mag in a 5″ radius aperture and correspond to dust masses between ∼10
4
and 10
6
kg, but with large uncertainties due to the unknown grain size distributions. However, the nominal mass estimates are on the same order of magnitude as the mini-outbursts at comet 9P/Tempel 1 and 67P/Churyumov-Gerasimenko, events that were notably lacking at comet 103P/Hartley 2. We compare the frequency of outbursts at the four comets, and suggest that the surface of 46P has large-scale (∼10–100 m) roughness that is intermediate to that of 67P and 103P, if not similar to the latter. The strength of the outbursts appear to be correlated with time since the last event, but a physical interpretation with respect to solar insolation is lacking. We also examine Hubble Space Telescope images taken about two days following a near-perihelion outburst. No evidence for macroscopic ejecta was found in the image, with a limiting radius of about 2 m.
Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a ...general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300−10307. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201−18209. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.
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Context.
Brown dwarfs are transition objects between stars and planets that are still poorly understood, for which several competing mechanisms have been proposed to describe their formation. Mass ...measurements are generally difficult to carry out for isolated objects as well as for brown dwarfs orbiting low-mass stars, which are often too faint for a spectroscopic follow-up.
Aims.
Microlensing provides an alternative tool for the discovery and investigation of such faint systems. Here, we present an analysis of the microlensing event OGLE-2019-BLG-0033/MOA-2019-BLG-035, which is caused by a binary system composed of a brown dwarf orbiting a red dwarf.
Methods.
Thanks to extensive ground observations and the availability of space observations from
Spitzer,
it has been possible to obtain accurate estimates of all microlensing parameters, including the parallax, source radius, and orbital motion of the binary lens.
Results.
Following an accurate modeling process, we found that the lens is composed of a red dwarf with a mass of
M
1
= 0.149 ± 0.010
M
⊙
and a brown dwarf with a mass of
M
2
= 0.0463 ± 0.0031
M
⊙
at a projected separation of
a
⊥
= 0.585 au. The system has a peculiar velocity that is typical of old metal-poor populations in the thick disk. A percent-level precision in the mass measurement of brown dwarfs has been achieved only in a few microlensing events up to now, but will likely become more common in the future thanks to the
Roman
space telescope.
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Several protein-tyrosine phosphatases (PTPs) have been proposed to act as negative regulators of insulin signaling. Recent studies have shown increased insulin sensitivity and resistance to obesity ...in PTP1B knockout mice, thus pointing to this enzyme as a potential drug target in diabetes. Structure-based design, guided by PTP mutants and x-ray protein crystallography, was used to optimize a relatively weak, nonphosphorus, nonpeptide general PTP inhibitor (2-(oxalyl-amino)-benzoic acid) into a highly selective PTP1B inhibitor. This was achieved by addressing residue 48 as a selectivity determining residue. By introducing a basic nitrogen in the core structure of the inhibitor, a salt bridge was formed to Asp-48 in PTP1B. In contrast, the basic nitrogen causes repulsion in other PTPs containing an asparagine in the equivalent position resulting in a remarkable selectivity for PTP1B. Importantly, this was accomplished while retaining the molecular weight of the inhibitor below 300 g/mol.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Protein-tyrosine phosphatases (PTPs) are critically involved in regulation of signal transduction processes. Members of this class of enzymes are considered attractive therapeutic targets in several ...disease states, e.g. diabetes, cancer, and inflammation. However, most reported PTP inhibitors have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore embarked on identifying a general, reversible, competitive PTP inhibitor that could be used as a common scaffold for lead optimization for specific PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid (OBA) as a classical competitive inhibitor of several PTPs. X-ray crystallography of PTP1B complexed with OBA and related non-phosphate low molecular weight derivatives reveals that the binding mode of these molecules to a large extent mimics that of the natural substrate including hydrogen bonding to the PTP signature motif. In addition, binding of OBA to the active site of PTP1B creates a unique arrangement involving Asp181, Lys120, and Tyr46. PTP inhibitors are essential tools in elucidating the biological function of specific PTPs and they may eventually be developed into selective drug candidates. The unique enzyme kinetic features and the low molecular weight of OBA makes it an ideal starting point for further optimization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To identify the region(s) of the insulin receptor and the insulin-like growth factor I (IGF-I) receptor responsible for ligand specificity (high-affinity binding), expression vectors encoding soluble ...chimeric insulin/IGF-I receptors were prepared. The chimeric receptors were expressed in mammalian cells and partially purified. Binding studies revealed that a construct comprising an IGF-I receptor in which the 68 N-terminal amino acids of the insulin receptor α-subunit had replaced the equivalent IGF-I receptor segment displayed a markedly increased affinity for insulin. In contrast, the corresponding IGF-I receptor sequence is not critical for high-affinity IGF-I binding. It is shown that part of the cysteine-rich domain determines IGF-I specificity. We have previously shown that exchanging exons 1, 2, and 3 of the insulin receptor with the corresponding IGF-I receptor sequence results in loss of high affinity for insulin and gain of high affinity for IGF-I. Consequently, it is suggested that the ligand specificities of the two receptors (i.e., the sequences that discriminate between insulin and IGF-I) reside in different regions of a binding site with common features present in both receptors.
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