The physical properties of 12 eclipsing binaries of M-type dwarfs with superflare activity are characterized by combining the ground-based spectroscopic measurements and the photometric light curves obtained by the Kepler Space Telescope. All of these binary systems have Algol-type orbital configurations. The primary components are mostly of the early M-type dwarfs (M0–M3). Even though the occurrence rate of large flares with energy >1034 erg of the EBs is less than the hyperflaring M dwarfs, the corresponding cumulative flare frequency is in general about a factor of 10 higher than the single M dwarfs with flare activity. This might be the consequence of magnetic interaction between the primary and secondary component of individual binaries. The slow rotators are not as active as the fast rotators, some of which display a possible eclipsing effect in their flare activity.
We report the flare activity of Wolf 359, the fifth closest star to the Sun and a candidate exoplanet-hosting M dwarf. The star was a target of the Kepler/K2 mission and was observed by the EDEN project, a global network of 1–2 m class telescopes for detection and characterization of rocky exoplanets in the habitable zones of late-M dwarfs within 50 light year from the solar system. In the combination of the archived K2 data and our EDEN observations, a total of 872 flares have been detected, 861 with the K2 (860 in the short-cadence and 18 in the long-cadence data, with 17 long-cadence events having short-cadence counterparts) and 11 with EDEN. Wolf 359 has relatively strong flare activity even among flaring M dwarfs, in terms of the flare activity indicator (FA) defined as the integrated flare energy relative to the total stellar bolometric energy, where FA = ∑E f /∫L bol dt ∼ 8.93 × 10−5 for the long-cadence flares, whereas for K2 short cadence and EDEN flares, the FA values are somewhat larger, FA ≈ 6.67 × 10−4 and FA ≈ 5.25 × 10−4, respectively. Such a level of activity, in accordance with the rotation period (P rot), suggests the star to be in the saturation phase. The size of the starspots is estimated to be at least 1.87% ± 0.59% of the projected disk area of Wolf 359. We find no correlation of FA with the stellar rotational phase. Our analysis indicates a flare frequency distribution in a power-law form of dN / dE ∝ E − α with α = 2.13 ± 0.14, equivalent to an occurrence rate of flares E f ≥ 1031 erg about once per day and of superflares with E f ≥ 1033 erg approximately 10 times per year. These superflares may impact the habitability of system in multiple ways, the details of which are topics for future investigations.
HER2-ECD (human epidermal growth factor receptor 2 – extracellular domain) is a prominent therapeutic target validated for treating HER2-positive breast and gastric cancer, but HER2-specific therapeutic options for treating advanced gastric cancer remain limited. We have developed antibody-drug conjugates (ADCs), comprising IgG1 linked via valine-citrulline to monomethyl auristatin E, with potential to treat HER2-positive gastric cancer in humans. The antibodies optimally selected from the ADC discovery platform, which was developed to discover antibody candidates suitable for immunoconjugates from synthetic antibody libraries designed using antibody-antigen interaction principles, were demonstrated to be superior immunoconjugate targeting modules in terms of efficacy and off-target toxicity. In comparison with the two control humanized antibodies (trastuzumab and H32) derived from murine antibody repertoires, the antibodies derived from the synthetic antibody libraries had enhanced receptor-mediated internalization rate, which could result in ADCs with optimal efficacies. Along with the ADCs, two other forms of immunoconjugates (scFv-PE38KDEL and IgG1-AL1-PE38KDEL) were used to test the antibodies for delivering cytotoxic payloads to xenograft tumor models in vivo and to cultured cells in vitro. The in vivo experiments with the three forms of immunoconjugates revealed minimal off-target toxicities of the selected antibodies from the synthetic antibody libraries; the off-target toxicities of the control antibodies could have resulted from the antibodies’ propensity to target the liver in the animal models. Our ADC discovery platform and the knowledge gained from our in vivo tests on xenograft models with the three forms of immunoconjugates could be useful to anyone developing optimal ADC cancer therapeutics.
From a study of the light curves of the M dwarfs observed by the Kepler space telescope in its primary mission, a number of flare events with the peak flux increases reaching more than the nominal stellar luminosity have been found. One of them, KIC 9201463, produced an extreme flare with the peak flux increase jumping to five times the quiet-time value. In relative terms, this class of hyperflares is much stronger than the superflares of the solar-type stars and could have a very important influence on the atmospheric evolution and the potential development of biospheres of habitable super-Earths orbiting around M dwarf stars. A cross-correlation of the flare activities of some of these M dwarf stars and their Hα equivalent width (EW) values derived from the LAMOST project indicates that the Hα EW values can be used to monitor the occurrence of hyperflares as well as the level of flare activity of different classes of M dwarfs with fast to slow rotations, and hence the long-term environmental effects of star–planet interaction of exoplanets.
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