Recent Development: Varriale v. State: The State May Store and Use a Voluntarily Provided DNA Sample and Resultant Profile For Any Future Criminal Investigations, Unless the Suspect Provides an Express Limitation

The Court of Appeals of Maryland held that when a suspect does not expressly limit consent to DNA testing, the Fourth Amendment does not prevent the State from storing and using his voluntarily provided DNA in later, unrelated criminal investigations

Recent Development: Varriale v. State: The State May Store and Use a Voluntarily Provided DNA Sample and Resultant Profile For Any Future Criminal Investigations, Unless the Suspect Provides an Express Limitation

The Court of Appeals of Maryland held that when a suspect does not expressly limit consent to DNA testing, the Fourth Amendment does not prevent the State from storing and using his voluntarily provided DNA in later, unrelated criminal investigations

Facile formation of iodocyclobutenes by a ruthenium-catalyzed enyne cycloisomerization

Enynes bearing an iodide (bromide) at their alkyne terminus react with catalytic amounts of [Cp*Ru(MeCN)3]PF6 in DMF to give strained iodo(bromo)cyclobutene derivatives in good to excellent yields

The New Generation Planetary Population Synthesis (NGPPS). IV. Planetary systems around low-mass stars

Context. Previous theoretical works on planet formation around low-mass stars have often been limited to large planets and individual systems. As current surveys routinely detect planets down to terrestrial size in these systems, models have shifted toward a more holistic approach that reflects their diverse architectures. Aims. Here, we investigate planet formation around low-mass stars and identify differences in the statistical distribution of modeled planets. We compare the synthetic planet populations to observed exoplanets and we discuss the identified trends. Methods. We used the Generation III Bern global model of planet formation and evolution to calculate synthetic populations, while varying the central star from Solar-like stars to ultra-late M dwarfs. This model includes planetary migration, N-body interactions between embryos, accretion of planetesimals and gas, and the long-term contraction and loss of the gaseous atmospheres. Results. We find that temperate, Earth-sized planets are most frequent around early M dwarfs (0.3 M⊙–0.5 M⊙) and that they are more rare for Solar-type stars and late M dwarfs. The planetary mass distribution does not linearly scale with the disk mass. The reason behind this is attributed to the emergence of giant planets for M⋆ ≥ 0.5 M⊙, which leads to the ejection of smaller planets. Given a linear scaling of the disk mass with stellar mass, the formation of Earth-like planets is limited by the available amount of solids for ultra-late M dwarfs. For M⋆ ≥ 0.3 M⊙, however, there is sufficient mass in the majority of systems, leading to a similar amount of Exo-Earths going from M to G dwarfs. In contrast, the number of super-Earths and larger planets increases monotonically with stellar mass. We further identify a regime of disk parameters that reproduces observed M-dwarf systems such as TRAPPIST-1. However, giant planets around late M dwarfs, such as GJ 3512b, only form when type I migration is substantially reduced. Conclusions. We are able to quantify the stellar mass dependence of multi-planet systems using global simulations of planet formation and evolution. The results fare well in comparison to current observational data and predict trends that can be tested with future observations

The New Generation Planetary Population Synthesis (NGPPS). V. Predetermination of planet types in global core accretion models

Context. State-of-the-art planet formation models are now capable of accounting for the full spectrum of known planet types. This comes at the cost of an increasing complexity of the models, which calls into question whether established links between their initial conditions and the calculated planetary observables are preserved. Aims. In this paper, we take a data-driven approach to investigate the relations between clusters of synthetic planets with similar properties and their formation history. Methods. We trained a Gaussian mixture model on typical exoplanet observables computed by a global model of planet formation to identify clusters of similar planets. We then traced back the formation histories of the planets associated with them and pinpointed their differences. Using the cluster affiliation as labels, we trained a random forest classifier to predict planet species from properties of the originating protoplanetary disk. Results. Without presupposing any planet types, we identified four distinct classes in our synthetic population. They roughly correspond to the observed populations of (sub-)Neptunes, giant planets, and (super-)Earths, plus an additional unobserved class we denote as “icy cores”. These groups emerge already within the first 0.1 Myr of the formation phase and are predicted from disk properties with an overall accuracy of >90%. The most reliable predictors are the initial orbital distance of planetary nuclei and the total planetesimal mass available. Giant planets form only in a particular region of this parameter space that is in agreement with purely analytical predictions. Including N-body interactions between the planets decreases the predictability, especially for sub-Neptunes that frequently undergo giant collisions and turn into super-Earths. Conclusions. The processes covered by current core accretion models of planet formation are largely predictable and reproduce the known demographic features in the exoplanet population. The impact of gravitational interactions highlights the need for N-body integrators for realistic predictions of systems of low-mass planets

Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis

Introduction: BI 1015550 is a phosphodiesterase 4 (PDE4) inhibitor that has antifibrotic properties. Phase I and Ic studies were conducted to investigate the safety, tolerability and pharmacokinetics of BI 1015550 in healthy male subjects and patients with idiopathic pulmonary fibrosis (IPF). Methods: In the phase I study, 42 subjects were partially randomised to receive placebo or BI 1015550 in single rising doses of 36 mg and 48 mg, or multiple rising doses of 6 mg and 12 mg twice daily over 14 days. In the phase Ic study, 15 patients with IPF were randomised to receive 18 mg BI 1015550 or placebo twice daily for up to 12 weeks. For both studies, the primary endpoint was the number of subjects with drug-related adverse events (AEs). Results: In the Phase I study, drug-related AEs were reported for 50.0% of healthy male subjects treated with a single dose of BI 1015550, compared with 16.7% receiving placebo. For those receiving multiple doses, drug-related AEs were reported for 37.5% of those treated with BI 1015550 and 12.5% receiving placebo. The most frequently reported AEs by organ class were nervous system disorders, which were largely driven by headache. In the Phase Ic study, drug-related AEs were reported in 90.0% of patients treated with BI 1015550, compared with 60.0% of those receiving placebo. The most frequent AEs by organ class were gastrointestinal AEs. Conclusions: BI 1015550 had an acceptable safety profile in healthy male subjects and male and female patients with IPF, supporting further development in larger trials

The CARMENES search for exoplanets around M dwarfs -- Planet occurrence rates from a subsample of 71 stars

The CARMENES exoplanet survey of M dwarfs has obtained more than 18 000 spectra of 329 nearby M dwarfs over the past five years as part of its guaranteed time observations (GTO) program. We determine planet occurrence rates with the 71 stars from the GTO program for which we have more than 50 observations. We use injection-and-retrieval experiments on the radial-velocity (RV) time series to measure detection probabilities. We include 27 planets in 21 planetary systems in our analysis. We find 0.06+0.04-0.03 giant planets (100 M_Earth < M_pl sin i < 1000 M_Earth) per star in periods of up to 1000 d, but due to a selection bias this number could be up to a factor of five lower in the whole 329-star sample. The upper limit for hot Jupiters (orbital period of less than 10 d) is 0.03 planets per star, while the occurrence rate of planets with intermediate masses (10 M_Earth < M_pl sin i < 100 M_Earth) is 0.18+0.07-0.05 planets per star. Less massive planets with 1 M_Earth < M_pl sin i < 10 M_Earth are very abundant, with an estimated rate of 1.32+0.33-0.31 planets per star for periods of up to 100 d. When considering only late M dwarfs with masses M_star < 0.34 M_sol, planets more massive than 10 M_Earth become rare. Instead, low-mass planets with periods shorter than 10 d are significantly overabundant. For orbital periods shorter than 100 d, our results confirm the known stellar mass dependences from the Kepler survey: M dwarfs host fewer giant planets and at least two times more planets with M_pl sin i < 10 M_Earth than G-type stars. In contrast to previous results, planets around our sample of very low-mass stars have a higher occurrence rate in short-period orbits of less than 10 d. Our results demonstrate the need to take into account host star masses in planet formation models.Comment: 15 pages, 12 figures. Accepted for publication in Astronomy & Astrophysic

Salinomycin induces calpain and cytochrome c-mediated neuronal cell death

Salinomycin is a polyether antibiotic with properties of an ionophore, which is commonly used as cocciodiostatic drug and has been shown to be highly effective in the elimination of cancer stem cells (CSCs) both in vitro and in vivo. One important caveat for the potential clinical application of salinomycin is its marked neural and muscular toxicity. In the present study we show that salinomycin in concentrations effective against CSCs exerts profound toxicity towards both dorsal root ganglia as well as Schwann cells. This toxic effect is mediated by elevated cytosolic Na+ concentrations, which in turn cause an increase of cytosolic Ca2+ by means of Na+/Ca2+ exchangers (NCXs) in the plasma membrane as well as the mitochondria. Elevated Ca2+ then leads to calpain activation, which triggers caspase-dependent apoptosis involving caspases 12, 9 and 3. In addition, cytochrome c released from depolarized mitochondria directly activates caspase 9. Combined inhibition of calpain and the mitochondrial NCXs resulted in significantly decreased cytotoxicity and was comparable to caspase 3 inhibition. These findings improve our understanding of mechanisms involved in the pathogenesis of peripheral neuropathy and are important to devise strategies for the prevention of neurotoxic side effects induced by salinomycin

Structural insights into the catalytic mechanism of Trypanosoma cruzi GPXI (glutathione peroxidase-like enzyme I).

Current drug therapies against Trypanosoma cruzi, the causative agent of Chagas disease, have limited effectiveness and are highly toxic. T. cruzi-specific metabolic pathways that utilize trypanothione for the reduction of peroxides are being explored as potential novel therapeutic targets. In the present study we solved the X-ray crystal structure of one of the T. cruzi enzymes involved in peroxide reduction, the glutathione peroxidase-like enzyme TcGPXI (T. cruzi glutathione peroxidase-like enzyme I). We also characterized the wild-type, C48G and C96G variants of TcGPXI by NMR spectroscopy and biochemical assays. Our results show that residues Cys48 and Cys96 are required for catalytic activity. In solution, the TcGPXI molecule readily forms a Cys48-Cys96 disulfide bridge and the polypeptide segment containing Cys96 lacks regular secondary structure. NMR spectra of the reduced TcGPXI are indicative of a protein that undergoes widespread conformational exchange on an intermediate time scale. Despite the absence of the disulfide bond, the active site mutant proteins acquired an oxidized-like conformation as judged from their NMR spectra. The protein that was used for crystallization was pre-oxidized by t-butyl hydroperoxide; however, the electron density maps clearly showed that the active site cysteine residues are in the reduced thiol form, indicative of X-ray-induced reduction. Our crystallographic and solution studies suggest a level of structural plasticity in TcGPXI consistent with the requirement of the atypical two-cysteine (2-Cys) peroxiredoxin-like mechanism implied by the behaviour of the Cys48 and Cys96 mutant proteins

HD 213885b: a transiting 1-d-period super-Earth with an Earth-like composition around a bright (V = 7.9) star unveiled by TESS

We report the discovery of the 1.008-d, ultrashort period (USP) super-Earth HD 213885b (TOI-141b) orbiting the bright (V = 7.9) star HD 213885 (TOI-141, TIC 403224672), detected using photometry from the recently launched TESS mission. Using FEROS, HARPS, and CORALIE radial velocities, we measure a precise mass of 8.8 ± 0.6 M⊕ for this 1.74 ± 0.05 R⊕ exoplanet, which provides enough information to constrain its bulk composition – similar to Earth’s but enriched in iron. The radius, mass, and stellar irradiation of HD 213885b are, given our data, very similar to 55 Cancri e, making this exoplanet a good target to perform comparative exoplanetology of short period, highly irradiated super-Earths. Our precise radial velocities reveal an additional 4.78-d signal which we interpret as arising from a second, non-transiting planet in the system, HD 213885c, whose minimum mass of 19.9 ± 1.4 M⊕ makes it consistent with being a Neptune-mass exoplanet. The HD 213885 system is very interesting from the perspective of future atmospheric characterization, being the second brightest star to host an USP transiting super-Earth (with the brightest star being, in fact, 55 Cancri). Prospects for characterization with present and future observatories are discussed