Rethinking Equitable Estoppel in Patent Law

In almost every context, the Federal Circuit has used estoppel doctrines to provide protection to parties from some sort of injustice. Yet recently, with equitable estoppel, the Federal Circuit has decided to infuse concepts of Article III justiciability to justify limiting the doctrine as only applicable to issued patents. In doing so, the Federal Circuit has ignored the long history behind equitable estoppel in favor of a rule that is improperly rationalized by the Constitution. This note argues that Federal Circuit\u27s recent equitable estoppel jurisprudence is inconsistent with equity\u27s goal of fairness and presents a new theory of equitable estoppel — inchoate estoppel — which would create fairer outcomes for patentees and defendants alike

Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

JWST/NIRCam Transmission Spectroscopy of the Nearby Sub-Earth GJ 341b

We present a JWST/NIRCam transmission spectrum from $3.9-5.0$ $\mu$m of the recently-validated sub-Earth GJ 341b ($\mathrm{R_P} = 0.92$ $\mathrm{R_{\oplus}}$, $\mathrm{T_{eq}} = 540$ K) orbiting a nearby bright M1 star ($\mathrm{d} = 10.4$ pc, $\mathrm{K_{mag}}=5.6$). We use three independent pipelines to reduce the data from the three JWST visits and perform several tests to check for the significance of an atmosphere. Overall, our analysis does not uncover evidence of an atmosphere. Our null hypothesis tests find that none of our pipelines' transmission spectra can rule out a flat line, although there is weak evidence for a Gaussian feature in two spectra from different pipelines (at 2.3 and $2.9\sigma$). However, the candidate features are seen at different wavelengths (4.3 $\mu$m vs 4.7 $\mu$m), and our retrieval analysis finds that different gas species can explain these features in the two reductions (CO$_2$ at $3.1\sigma$ compared to O$_3$ at $2.9\sigma$), suggesting that they are not real astrophysical signals. Our forward model analysis rules out a low mean molecular weight atmosphere ($< 350\times$ solar metallicity) to at least $3\sigma$, and disfavors CH$_4$-dominated atmospheres at $1-3\sigma$, depending on the reduction. Instead, the forward models find our transmission spectra are consistent with no atmosphere, a hazy atmosphere, or an atmosphere containing a species that does not have prominent molecular bands across the NIRCam/F444W bandpass, such as a water-dominated atmosphere. Our results demonstrate the unequivocal need for two or more transit observations analyzed with multiple reduction pipelines, alongside rigorous statistical tests, to determine the robustness of molecular detections for small exoplanet atmospheres.Comment: 25 pages, 18 figures, 6 tables. Accepted for publication in A

Double Trouble: Two Transits of the Super-Earth GJ 1132 b Observed with JWST NIRSpec G395H

The search for rocky planet atmospheres with JWST has focused on planets transiting M dwarfs. Such planets have favorable planet-to-star size ratios, enhancing the amplitude of atmospheric features. Since the expected signal strength of atmospheric features is similar to the single-transit performance of JWST, multiple observations are required to confirm any detection. Here, we present two transit observations of the rocky planet GJ 1132 b with JWST NIRSpec G395H, covering 2.8-5.2 $\mu$m. Previous HST WFC3 observations of GJ 1132 b were inconclusive, with evidence reported for either an atmosphere or a featureless spectrum based on analyses of the same dataset. Our JWST data exhibit substantial differences between the two visits. One transit is consistent with either a H$_2$O-dominated atmosphere containing ~1% CH$_4$ and trace N$_2$O ($\chi^{2}_{\nu}$ = 1.13) or stellar contamination from unocculted starspots ($\chi^{2}_{\nu}$ = 1.36). However, the second transit is consistent with a featureless spectrum. Neither visit is consistent with a previous report of HCN. Atmospheric variability is unlikely to explain the scale of the observed differences between the visits. Similarly, our out-of-transit stellar spectra show no evidence of changing stellar inhomogeneity between the two visits - observed 8 days apart, only 6.5% of the stellar rotation rate. We further find no evidence of differing instrumental systematic effects between visits. The most plausible explanation is an unlucky random noise draw leading to two significantly discrepant transmission spectra. Our results highlight the importance of multi-visit repeatability with JWST prior to claiming atmospheric detections for these small, enigmatic planets.Comment: 22 pages, 10 figures, 2 tables. Accepted for publication in ApJ Letters. Co-First Authors. Bonus materials and spectral data: https://doi.org/10.5281/zenodo.1000208

Superhelical Duplex Destabilization and the Recombination Position Effect

The susceptibility to recombination of a plasmid inserted into a chromosome varies with its genomic position. This recombination position effect is known to correlate with the average G+C content of the flanking sequences. Here we propose that this effect could be mediated by changes in the susceptibility to superhelical duplex destabilization that would occur. We use standard nonparametric statistical tests, regression analysis and principal component analysis to identify statistically significant differences in the destabilization profiles calculated for the plasmid in different contexts, and correlate the results with their measured recombination rates. We show that the flanking sequences significantly affect the free energy of denaturation at specific sites interior to the plasmid. These changes correlate well with experimentally measured variations of the recombination rates within the plasmid. This correlation of recombination rate with superhelical destabilization properties of the inserted plasmid DNA is stronger than that with average G+C content of the flanking sequences. This model suggests a possible mechanism by which flanking sequence base composition, which is not itself a context-dependent attribute, can affect recombination rates at positions within the plasmid

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

Ontogeny-Driven rDNA Rearrangement, Methylation, and Transcription, and Paternal Influence

Gene rearrangement occurs during development in some cell types and this genome dynamics is modulated by intrinsic and extrinsic factors, including growth stimulants and nutrients. This raises a possibility that such structural change in the genome and its subsequent epigenetic modifications may also take place during mammalian ontogeny, a process undergoing finely orchestrated cell division and differentiation. We tested this hypothesis by comparing single nucleotide polymorphism-defined haplotype frequencies and DNA methylation of the rDNA multicopy gene between two mouse ontogenic stages and among three adult tissues of individual mice. Possible influences to the genetic and epigenetic dynamics by paternal exposures were also examined for Cr(III) and acid saline extrinsic factors. Variables derived from litters, individuals, and duplicate assays in large mouse populations were examined using linear mixed-effects model. We report here that active rDNA rearrangement, represented by changes of haplotype frequencies, arises during ontogenic progression from day 8 embryos to 6-week adult mice as well as in different tissue lineages and is modifiable by paternal exposures. The rDNA methylation levels were also altered in concordance with this ontogenic progression and were associated with rDNA haplotypes. Sperm showed highest level of methylation, followed by lungs and livers, and preferentially selected haplotypes that are positively associated with methylation. Livers, maintaining lower levels of rDNA methylation compared with lungs, expressed more rRNA transcript. In vitro transcription demonstrated haplotype-dependent rRNA expression. Thus, the genome is also dynamic during mammalian ontogeny and its rearrangement may trigger epigenetic changes and subsequent transcriptional controls, that are further influenced by paternal exposures

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte