We present updated orbital elements for the Wolf–Rayet (WR) binary WR 140 (HD 193793; WC7pd + O5.5fc). The new orbital elements were derived using previously published measurements along with 160 new radial velocity measurements across the 2016 periastron passage of WR 140. Additionally, four new measurements of the orbital astrometry were collected with the CHARA Array. With these measurements, we derive stellar masses of $M_{\rm WR} = 10.31\pm 0.45 \, \mathrm{M}_\odot$ and $M_{\rm O} = 29.27\pm 1.14 \, \mathrm{M}_{\odot }$. We also include a discussion of the evolutionary history of this system from the Binary Population and Spectral Synthesis model grid to show that this WR star likely formed primarily through mass-loss in the stellar winds, with only a moderate amount of mass lost or transferred through binary interactions.
A series of compounds with different R groups, such as aliphatic and aromatic amides, carbamates, sulfonamides, and ureas, has been tested and all of the compounds showed very similar affinities to E-selectin. Compounds 3 b ± d were selected as representative examples. See: R.[20] NMR spectroscopic measurements were carried out on a Varian UnityPlus 600 spectrometer operating at a frequency of 600 MHz. All experiments were carried out at 25 8C with compound concentrations of approximately 10 mm in D 2 O solutions. ROESY experiments were carried out with mixing times of 150 ms. For some compounds, ROESY spectra were recorded using 50 ms and 100 ms mixing times, and the results were indistinguishable. Typical acquisition times in the direct and indirect dimensions were 340 ms and 64 ms, respectively. The data were zero-filled to yield a digital resolution of 1.46 Hz and 2.92 Hz, respectively. For bound 2, NOE values were extracted from transfer NOE spectra (see ref.[7b]). Signal integration was performed using Varian VNMR software. All NOEs were normalized using intraglycosidic NOE enhancements such as H1 G ± H3 G and H4 F ± H5 F . The distances between these hydrogens are given by the chair conformations of fucose and galactose and should be very similar for compounds 2, 4, 5, and 6. It should be noted that the measured NOE values do not refer to a distinct conformation of the molecule but represent the weighted mean distance over several coexisting low energy conformations.[21] a)
<div>Abstract<p>After significant effort over the last 30 years, antibody–drug conjugates (ADC) have recently gained momentum as a therapeutic modality, and nine ADCs have been approved by the FDA to date, with additional ADCs in late stages of development. Here, we introduce dolaflexin, a novel ADC technology that overcomes key limitations of the most common ADC platforms with two key features: a higher drug-to-antibody ratio and a novel auristatin with a controlled bystander effect. The novel, cell permeable payload, auristatin F-hydroxypropylamide, undergoes metabolic conversion to the highly potent, but less cell permeable auristatin F to balance the bystander effect through drug trapping within target cells. We conducted studies in mice, rats, and cynomolgus monkeys to complement <i>in vitro</i> characterization and contrasted the performance of dolaflexin with regard to antitumor activity, pharmacokinetic properties, and safety in comparison with the ADC platform utilized in the approved ADC ado-trastuzumab emtansine (T-DM1). A HER2-targeted dolaflexin ADC was shown to have a much lower threshold of antigen expression for potent cell killing <i>in vitro</i>, was effective <i>in vivo</i> in tumors with low HER2 expression, and induced tumor regressions in a xenograft model that is resistant to T-DM1.</p></div>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.