When it Pays to Rush: Interpreting Morphogen Gradients Prior to Steady-State

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state.Comment: 18 pages, 3 figure

Spouses Need Not Apply: The Legality of Antinepotism and No-Spouse Rules

Over the last three decades, there have been significant increases in labor force participation by women. Initially, this increase was fueled by the entry of single, childless women into the labor market. Married women primarily dedicated their efforts to home care concerns. However, in recent years, a new trend has emerged as the levels of market work undertaken by married women have increased relative to those of unmarried women

The California-Kepler Survey. IV. Metal-rich Stars Host a Greater Diversity of Planets

Probing the connection between a star's metallicity and the presence and properties of any associated planets offers an observational link between conditions during the epoch of planet formation and mature planetary systems. We explore this connection by analyzing the metallicities of Kepler target stars and the subset of stars found to host transiting planets. After correcting for survey incompleteness, we measure planet occurrence: the number of planets per 100 stars with a given metallicity $M$. Planet occurrence correlates with metallicity for some, but not all, planet sizes and orbital periods. For warm super-Earths having $P = 10-100$ days and $R_P = 1.0-1.7~R_E$, planet occurrence is nearly constant over metallicities spanning $-$0.4 dex to +0.4 dex. We find 20 warm super-Earths per 100 stars, regardless of metallicity. In contrast, the occurrence of warm sub-Neptunes ($R_P = 1.7-4.0~R_E$) doubles over that same metallicity interval, from 20 to 40 planets per 100 stars. We model the distribution of planets as $d f \propto 10^{\beta M} d M$, where $\beta$ characterizes the strength of any metallicity correlation. This correlation steepens with decreasing orbital period and increasing planet size. For warm super-Earths $\beta = -0.3^{+0.2}_{-0.2}$, while for hot Jupiters $\beta = +3.4^{+0.9}_{-0.8}$. High metallicities in protoplanetary disks may increase the mass of the largest rocky cores or the speed at which they are assembled, enhancing the production of planets larger than 1.7 $R_E$. The association between high metallicity and short-period planets may reflect disk density profiles that facilitate the inward migration of solids or higher rates of planet-planet scattering.Comment: 32 pages, 15 figures, 9 tables, accepted for publication in The Astronomical Journa

Orbital Orientations of Exoplanets: HAT-P-4b is Prograde and HAT-14b is Retrograde

We present observations of the Rossiter-McLaughlin effect for two exoplanetary systems, revealing the orientations of their orbits relative to the rotation axes of their parent stars. HAT-P-4b is prograde, with a sky-projected spin-orbit angle of λ = –4.9 ± 11.9 deg. In contrast, HAT-P-14b is retrograde, with λ = 189.1 ± 5.1 deg. These results conform with a previously noted pattern among the stellar hosts of close-in giant planets: hotter stars have a wide range of obliquities and cooler stars have low obliquities. This, in turn, suggests that three-body dynamics and tidal dissipation are responsible for the short-period orbits of many exoplanets. In addition, our data revealed a third body in the HAT-P-4 system, which could be a second planet or a companion star

Constraints on the Obliquities of Kepler Planet-Hosting Stars

Stars with hot Jupiters have obliquities ranging from 0-180 degrees, but relatively little is known about the obliquities of stars with smaller planets. Using data from the California-Kepler Survey, we investigate the obliquities of stars with planets spanning a wide range of sizes, most of which are smaller than Neptune. First, we identify 156 planet hosts for which measurements of the projected rotation velocity (vsini) and rotation period are both available. By combining estimates of v and vsini, we find nearly all the stars to be compatible with high inclination, and hence, low obliquity (less than about 20 degrees). Second, we focus on a sample of 159 hot stars (> 6000K) for which vsini is available but not necessarily the rotation period. We find 6 stars for which vsini is anomalously low, an indicator of high obliquity. Half of these have hot Jupiters, even though only 3% of the stars that were searched have hot Jupiters. We also compare the vsini distribution of the hot stars with planets to that of 83 control stars selected without prior knowledge of planets. The mean vsini of the control stars is lower than that of the planet hosts by a factor of approximately pi/4, as one would expect if the planet hosts have low obliquities. All these findings suggest that the Kepler planet-hosting stars generally have low obliquities, with the exception of hot stars with hot Jupiters.Comment: AJ, in pres

Systemic treatment of advanced and metastatic urothelial cancer: The landscape in Australia

The 5-year survival rate of metastatic urothelial carcinoma (mUC) is estimated to be as low as 5%. Currently, systemic platinum-based chemotherapy followed by avelumab maintenance therapy is the only first-line treatment for mUC that has an overall survival benefit. Cisplatin-based chemotherapy (usually in combination with gemcitabine) is the preferred treatment but carboplatin is substituted where contraindications to cisplatin exist. Treatment with immune checkpoint inhibitors, antibody-drug conjugates, and kinase inhibitors has not yet demonstrated superiority to chemotherapy as first-line therapy and remains investigational in this setting. A recent media release indicates that chemotherapy plus nivolumab gives an OS advantage as first-line treatment but results of this study have not yet been made public. Pembrolizumab remains an option in those having primary progression on first-line chemotherapy or within 12 months of neoadjuvant chemotherapy. The antibody-drug conjugate, enfortumab vedotin has TGA approval for patients whose cancer has progressed following chemotherapy and immunotherapy and has just received a positive Pharmaceutical Benefits Scheme recommendation. The use of molecular screens for somatic genetic mutations, gene amplifications, and protein expression is expanding as drugs that target such abnormalities show promise. However, despite these advances, a substantial proportion of patients with mUC have significant barriers to receiving any treatment, including advancing age, frailty, and comorbidities, and less toxic, effective therapies are needed

The California-Kepler Survey. III. A Gap in the Radius Distribution of Small Planets

The size of a planet is an observable property directly connected to the physics of its formation and evolution. We used precise radius measurements from the California-Kepler Survey (CKS) to study the size distribution of 2025 $\textit{Kepler}$ planets in fine detail. We detect a factor of $\geq$2 deficit in the occurrence rate distribution at 1.5-2.0 R$_{\oplus}$. This gap splits the population of close-in ($P$ < 100 d) small planets into two size regimes: R$_P$ < 1.5 R$_{\oplus}$ and R$_P$ = 2.0-3.0 R$_{\oplus}$, with few planets in between. Planets in these two regimes have nearly the same intrinsic frequency based on occurrence measurements that account for planet detection efficiencies. The paucity of planets between 1.5 and 2.0 R$_{\oplus}$ supports the emerging picture that close-in planets smaller than Neptune are composed of rocky cores measuring 1.5 R$_{\oplus}$ or smaller with varying amounts of low-density gas that determine their total sizes.Comment: Paper III in the California-Kepler Survey series, accepted to the Astronomical Journa

Friends of Hot Jupiters II: No Correspondence Between Hot-Jupiter Spin-Orbit Misalignment and the Incidence of Directly Imaged Stellar Companions

Multi-star systems are common, yet little is known about a stellar companion's influence on the formation and evolution of planetary systems. For instance, stellar companions may have facilitated the inward migration of hot Jupiters towards to their present day positions. Many observed short period gas giant planets also have orbits that are misaligned with respect to their star's spin axis, which has also been attributed to the presence of a massive outer companion on a non-coplanar orbit. We present the results of a multi-band direct imaging survey using Keck NIRC2 to measure the fraction of short period gas giant planets found in multi-star systems. Over three years, we completed a survey of 50 targets ("Friends of Hot Jupiters") with 27 targets showing some signature of multi-body interaction (misaligned or eccentric orbits) and 23 targets in a control sample (well-aligned and circular orbits). We report the masses, projected separations, and confirmed common proper motion for the 19 stellar companions found around 17 stars. Correcting for survey incompleteness, we report companion fractions of $48\%\pm9\%$, $47\%\pm12\%$, and $51\%\pm13\%$ in our total, misaligned/eccentric, and control samples, respectively. This total stellar companion fraction is $2.8\,\sigma$ larger than the fraction of field stars with companions approximately $50-2000\,$AU. We observe no correlation between misaligned/eccentric hot Jupiter systems and the incidence of stellar companions. Combining this result with our previous radial velocity survey, we determine that $72\% \pm 16\%$ of hot Jupiters are part of multi-planet and/or multi-star systems.Comment: typos and references updated; 25 pages, 7 figures and 10 tables, accepted for publication in Ap

The California-Kepler Survey V. Peas in a Pod: Planets in a Kepler Multi-planet System are Similar in Size and Regularly Spaced

We have established precise planet radii, semimajor axes, incident stellar fluxes, and stellar masses for 909 planets in 355 multi-planet systems discovered by Kepler. In this sample, we find that planets within a single multi-planet system have correlated sizes: each planet is more likely to be the size of its neighbor than a size drawn at random from the distribution of observed planet sizes. In systems with three or more planets, the planets tend to have a regular spacing: the orbital period ratios of adjacent pairs of planets are correlated. Furthermore, the orbital period ratios are smaller in systems with smaller planets, suggesting that the patterns in planet sizes and spacing are linked through formation and/or subsequent orbital dynamics. Yet, we find that essentially no planets have orbital period ratios smaller than $1.2$, regardless of planet size. Using empirical mass-radius relationships, we estimate the mutual Hill separations of planet pairs. We find that $93\%$ of the planet pairs are at least 10 mutual Hill radii apart, and that a spacing of $\sim20$ mutual Hill radii is most common. We also find that when comparing planet sizes, the outer planet is larger in $65 \pm 0.4\%$ of cases, and the typical ratio of the outer to inner planet size is positively correlated with the temperature difference between the planets. This could be the result of photo-evaporation.Comment: Published in The Astronomical Journal. 15 pages, 17 figure

The California-Kepler Survey. II. Precise Physical Properties of 2025 Kepler Planets and Their Host Stars

We present stellar and planetary properties for 1305 Kepler Objects of Interest (KOIs) hosting 2025 planet candidates observed as part of the California-Kepler Survey. We combine spectroscopic constraints, presented in Paper I, with stellar interior modeling to estimate stellar masses, radii, and ages. Stellar radii are typically constrained to 11%, compared to 40% when only photometric constraints are used. Stellar masses are constrained to 4%, and ages are constrained to 30%. We verify the integrity of the stellar parameters through comparisons with asteroseismic studies and Gaia parallaxes. We also recompute planetary radii for 2025 planet candidates. Because knowledge of planetary radii is often limited by uncertainties in stellar size, we improve the uncertainties in planet radii from typically 42% to 12%. We also leverage improved knowledge of stellar effective temperature to recompute incident stellar fluxes for the planets, now precise to 21%, compared to a factor of two when derived from photometry.Comment: 13 pages, 4 figures, 4 tables, accepted for publication in AJ; full versions of tables 3 and 4 are include