• Canada

Metastatic breast cancer is a very heterogeneous disease. Recent advances in genomic sequencing have revealed genetic diversity between patients and across distinct subclonal cell populations within the same patient that may evolve across metastatic tumor sites and during treatment. With the increasing availability of commercial and laboratory-developed tests that can detect genomic alterations from patient tumor and blood samples, translating this knowledge into improved clinical care remains a challenge. The goals of this review are to outline the clinical relevance of tumor genomic heterogeneity and clonal evolution, to help clinicians understand how to interpret genomic testing reports, and to provide an overview of recurrent genomic alterations that may be relevant for clinical trials with investigational drug treatments.

We present an analysis of six independent on-sky datasets taken with the Keck-II/NIRC2 instrument. Using the off-axis point spread function (PSF) reconstruction software AIROPA, we extract stellar astrometry, photometry, and other fitting metrics in order to characterize the performance of this package. We test the effectiveness of AIROPA to reconstruct the PSF across the field of view in varying atmospheric conditions, number and location of PSF reference stars, stellar crowding and telescope position angle (PA). We compare the astrometric precision and fitting residuals between a static PSF model and a spatially varying PSF model that incorporates instrumental aberrations and atmospheric turbulence during exposures. Most of the fitting residuals we measure show little to no improvement in the variable-PSF mode over the single-PSF mode. For one of the data sets, we find photometric performance is significantly improved (by ${\sim}10\times$) by measuring the trend seen in photometry as a function of off-axis location. For nearly all other metrics we find comparable astrometric and photometric precision across both PSF modes, with a ${\sim}13$% smaller astrometric uncertainty in variable-PSF mode in the best case. We largely confirm that the spatially variable PSF does not significantly improve the astrometric and other PSF fitting residuals over the static PSF for on-sky observations. We attribute this to unaccounted instrumental aberrations that are not characterized through afternoon adaptive optics (AO) bench calibrations. Comment: 23 pages, 13 figures, submitted to JATIS

Frontiers in immunology 12, 701275 (2021). doi:10.3389/fimmu.2021.701275 Published by Frontiers Media, Lausanne

A conserved feature of the midblastula transition (MBT) is a requirement for a functional DNA replication checkpoint to coordinate cell cycle remodeling and zygotic genome activation (ZGA). We have investigated what triggers this checkpoint during Drosophila embryogenesis. We find that the magnitude of the checkpoint scales with the quantity of transcriptionally engaged DNA. Measuring RNA Polymerase II (Pol II) binding at 20-minute intervals over the course of ZGA reveals that the checkpoint coincides with widespread de novo recruitment of Pol II that precedes and does not require a functional checkpoint. This recruitment drives slowing or stalling of DNA replication at transcriptionally engaged loci. Reducing Pol II recruitment in zelda mutants both reduces replication stalling and bypasses the requirement for a functional checkpoint. This suggests a model where the checkpoint functions as a feedback mechanism to remodel the cell cycle in response to nascent ZGA.

Restraining and secluding children living in residential facilities, though controversial, are commonly practiced by staff to manage disruptive behavior. In an effort to address some of the ongoing issues about the practice, this article examined the reasons for their use, their theoretical underpinnings, and extant empirical evidence in support of the theories. It is suggested that the current array of theories be updated and comprehensive research programs be encouraged to assess their clinical utility with various populations in a variety of settings.

We study the fingering instability that occurs at the contact line of a thin sheet of a yield-stress fluid flowing down an incline. We derive an expression for the wavelength of the finger pattern as a function of inclination angle for a Herschel-Bulkley fluid. The wavelength is predicted to diverge at a finite angle which is related to the yield stress of the fluid. We also measure the wavelength of the finger pattern with suspensions of bentonite clay in water. Our experimental results agree well with the theoretical prediction.

Abstract In geostatistical simulation, a realization represents one possible outcome of the spatial uncertainty model. Tens to hundreds of realizations are generated in order to understand response property variation. There are ways to summarize local uncertainty, but visualizing all realizations is important to understand joint uncertainty between multiple locations. There is no straightforward manner to visualize all realizations at the same time or in sequence. This paper presents a new method to sequentially display multiple geostatistical realizations. The proposed algorithm performs an ordering of the visible portion of the realizations (images), according to the distance between realizations. The concept of distance corresponds to the differences computed cell by cell for every realization pair or to the differences computed from a moving window filtering applied to each realization. To define an optimal sequence of realizations, the shortest path route through the realizations is established by a simulated annealing technique. The gradual transition between realizations is enhanced by an image morphing technique where intermediate images are introduced between the original images. The final result consists of an animation that shows the sequence of realizations and allows better understanding of the uncertainty model.