Comparative Studies of Disordered Proteins with Similar Sequences: Application to Aβ40 and Aβ42

Quantitative comparisons of intrinsically disordered proteins (IDPs) with similar sequences, such as mutant forms of the same protein, may provide insights into IDP aggregation—a process that plays a role in several neurodegenerative disorders. Here we describe an approach for modeling IDPs with similar sequences that simplifies the comparison of the ensembles by utilizing a single library of structures. The relative population weights of the structures are estimated using a Bayesian formalism, which provides measures of uncertainty in the resulting ensembles. We applied this approach to the comparison of ensembles for Aβ40 and Aβ42. Bayesian hypothesis testing finds that although both Aβ species sample β-rich conformations in solution that may represent prefibrillar intermediates, the probability that Aβ42 samples these prefibrillar states is roughly an order of magnitude larger than the frequency in which Aβ40 samples such structures. Moreover, the structure of the soluble prefibrillar state in our ensembles is similar to the experimentally determined structure of Aβ that has been implicated as an intermediate in the aggregation pathway. Overall, our approach for comparative studies of IDPs with similar sequences provides a platform for future studies on the effect of mutations on the structure and function of disordered proteins

Appropriate use criteria for endotracheal suction interventions in mechanically ventilated children : the RAND/UCLA development process

Objectives: Endotracheal suction is an invasive airway clearance technique used in mechanically ventilated children. This article outlines the methods used to develop appropriate use criteria for endotracheal suction interventions in mechanically ventilated paediatric patients. Methods: The RAND Corporation and University of California, Los Angeles Appropriateness Method was used to develop paediatric appropriate use criteria. This included the following sequential phases of defining scope and key terms, a literature review and synthesis, expert multidisciplinary panel selection, case scenario development, and appropriateness ratings by an interdisciplinary expert panel over two rounds. The panel comprised experts in the fields of paediatric and neonatal intensive care, respiratory medicine, infectious diseases, critical care nursing, implementation science, retrieval medicine, and education. Case scenarios were developed iteratively by interdisciplinary experts and derived from common applications or anticipated intervention uses, as well as from current clinical practice guidelines and results of studies examining interventions efficacy and safety. Scenarios were rated on a scale of 1 (harm outweighs benefit) to 9 (benefit outweighs harm), to define appropriate use (median: 7 to 9), uncertain use (median: 4 to 6), and inappropriate use (median: 1 to 3) of endotracheal suction interventions. Scenarios were than classified as a level of appropriateness. Conclusions: The RAND Corporation/University of California, Los Angeles Appropriateness Method provides a thorough and transparent method to inform development of the first appropriate use criteria for endotracheal suction interventions in paediatric patients

WASP-107b’s Density Is Even Lower: A Case Study for the Physics of Planetary Gas Envelope Accretion and Orbital Migration

With a mass in the Neptune regime and a radius of Jupiter, WASP-107b presents a challenge to planet formation theories. Meanwhile, the planet's low surface gravity and the star's brightness also make it one of the most favorable targets for atmospheric characterization. Here, we present the results of an extensive 4 yr Keck/HIRES radial-velocity (RV) follow-up program of the WASP-107 system and provide a detailed study of the physics governing the accretion of the gas envelope of WASP-107b. We reveal that WASP-107b's mass is only 1.8 Neptune masses (M_b = 30.5 ± 1.7 M_⊕). The resulting extraordinarily low density suggests that WASP-107b has a H/He envelope mass fraction of >85% unless it is substantially inflated. The corresponding core mass of <4.6 M_⊕ at 3σ is significantly lower than what is traditionally assumed to be necessary to trigger massive gas envelope accretion. We demonstrate that this large gas-to-core mass ratio most plausibly results from the onset of accretion at gsim1 au onto a low-opacity, dust-free atmosphere and subsequent migration to the present-day a_b = 0.0566 ± 0.0017 au. Beyond WASP-107b, we also detect a second, more massive planet (M_c sin i = 0.36 ± 0.04MJ ) on a wide eccentric orbit (e _c = 0.28 ± 0.07) that may have influenced the orbital migration and spin–orbit misalignment of WASP-107b. Overall, our new RV observations and envelope accretion modeling provide crucial insights into the intriguing nature of WASP-107b and the system's formation history. Looking ahead, WASP-107b will be a keystone planet to understand the physics of gas envelope accretion

Orientation Sensitivity at Different Stages of Object Processing: Evidence from Repetition Priming and Naming

An ongoing debate in the object recognition literature centers on whether the shape representations used in recognition are coded in an orientation-dependent or orientation-invariant manner. In this study, we asked whether the nature of the object representation (orientation-dependent vs orientation-invariant) depends on the information-processing stages tapped by the task

Characterizing K2 Candidate Planetary Systems Orbiting Low-mass Stars. III. A High Mass and Low Envelope Fraction for the Warm Neptune K2-55b

K2-55b is a Neptune-sized planet orbiting a K7 dwarf with a radius of , a mass of 0.688 ± 0.069 M⊙, and an effective temperature of 4300^(+107)_(-100) K. Having characterized the host star using near-infrared spectra obtained at IRTF/SpeX, we observed a transit of K2-55b with Spitzer/Infrared Array Camera (IRAC) and confirmed the accuracy of the original K2 ephemeris for future follow-up transit observations. Performing a joint fit to the Spitzer/IRAC and K2 photometry, we found a planet radius of 4.41^(+0.32)_(-0.28) R⊕, an orbital period of 2.84927265^(+6.87 x 10^(-6))_(-6.42 x 10^(-6)) days, and an equilibrium temperature of roughly 900 K. We then measured the planet mass by acquiring 12 radial velocity (RV) measurements of the system using the High Resolution Echelle Spectrometer on the 10 m Keck I Telescope. Our RV data set precisely constrains the mass of K2-55b to 43.13^(+5.98)_(-5.80) M⊕, indicating that K2-55b has a bulk density of 2.8^(+0.8)_(-0.6) g cm^(−3) and can be modeled as a rocky planet capped by a modest H/He envelope (M_(envelope) = 12 ± 3% M_p ). K2-55b is denser than most similarly sized planets, raising the question of whether the high planetary bulk density of K2-55b could be attributed to the high metallicity of K2-55. The absence of a substantial volatile envelope despite the high mass of K2-55b poses a challenge to current theories of gas giant formation. We posit that K2-55b may have escaped runaway accretion by migration, late formation, or inefficient core accretion, or that K2-55b was stripped of its envelope by a late giant impact