DE-STRESS:A user-friendly web application for the evaluation of protein designs

De novo protein design is a rapidly growing field, and there are now many interesting and useful examples of designed proteins in the literature. However, most designs could be classed as failures when characterised in the lab, usually as a result of low expression, misfolding, aggregation or lack of function. This high attrition rate makes protein design unreliable and costly. It is possible that some of these failures could be caught earlier in the design process if it were quick and easy to generate information and a set of high-quality metrics regarding designs, which could be used to make reproducible and data-driven decisions about which designs to characterise experimentally. We present DE-STRESS (DEsigned STRucture Evaluation ServiceS), a web application for evaluating structural models of designed and engineered proteins. DE-STRESS has been designed to be simple, intuitive to use and responsive. It provides a wealth of information regarding designs, as well as tools to help contextualise the results and formally describe the properties that a design requires to be fit for purpose

SweetSpot: Near-Infrared Observations of Thirteen Type Ia Supernovae from a New NOAO Survey Probing the Nearby Smooth Hubble Flow

We present 13 Type Ia supernovae (SNe Ia) observed in the restframe near-infrared (NIR) from 0.02 < z < 0.09 with the WIYN High-resolution Infrared Camera (WHIRC) on the WIYN 3.5-m telescope. With only 1-3 points per light curve and a prior on the time of maximum from the spectrum used to type the object we measure an H-band dispersion of spectroscopically normal SNe Ia of 0.164 mag. These observations continue to demonstrate the improved standard brightness of SNe Ia in H-band even with limited data. Our sample includes two SNe Ia at z ~ 0.09, which represent the most distant restframe NIR H-band observations published to date. This modest sample of 13 NIR SNe Ia represent the pilot sample for "SweetSpot" - a three-year NOAO Survey program that will observe 144 SNe Ia in the smooth Hubble flow. By the end of the survey we will have measured the relative distance to a redshift of z ~ 0.05 to 1%. Nearby Type Ia supernova (SN Ia) observations such as these will test the standard nature of SNe Ia in the restframe NIR, allow insight into the nature of dust, and provide a critical anchor for future cosmological SN Ia surveys at higher redshift.Comment: 36 pages, 8 figures, Submitted to Ap

Principles for Responsibility Sharing: Proximity, Culpability, Moral Accountability, and Capability

In this Essay, we explore how responsibility based on culpability, moral accountability, and capability can improve the current regime that rests on responsibility by proximity. In doing so, we draw on the 2017 Model International Mobility Convention (MIMC), a model convention drafted by a commission of independent experts and currently supported as a project of the Carnegie Council for Ethics in International Affairs

The African Lungfish (\u3cem\u3eProtopterus dolloi\u3c/em\u3e): Ionoregulation and Osmoregulation in a Fish out of Water

Although urea production and metabolism in lungish have been thoroughly studied, we have little knowledge of how internal osmotic and electrolyte balance are controlled during estivation or in water. We tested the hypothesis that, compared with the body surface of teleosts, the slender African lungfish (Protopterus dolloi) body surface was relatively impermeable to water, Na+ and Cl- due to its greatly reduced gills. Accordingly, we measured the tritiated water (3H-H2O) flux in P. dolloi in water and during air exposure. In water, 3H-H2O efflux was comparable with the lowest measurements reported in freshwater teleosts, with a rate constant (K) of 17.6% body water h-1. Unidirectional ion fluxes, measured using 22Na+ and 36Cl-, indicated that Na+ and Cl- influx was more than 90% lower than values reported in most freshwater teleosts. During air exposure, a cocoon formed within 1 wk that completely covered the dorsolateral body surface. However, there were no disturbances to blood osmotic or ion (Na+, Cl-) balance, despite seven- to eightfold increases in plasma urea after 20 wk. Up to 13-fold increases in muscle urea (on a dry-weight basis) were the likely explanation for the 56% increase in muscle water content observed after 20 wk of air exposure. The possibility that muscle acted as a “water reservoir” during air exposure was supported by the 20% decline in body mass observed during subsequent reimmersion in water. This decline in body mass was equivalent to 28 mL water in a 100-g animal and was very close to the calculated net water gain (approximately 32 mL) observed during the 20-wk period of air exposure. Tritiated water and unidirectional ion fluxes on air-exposed lungfish revealed that the majority of water and ion exchange was via the ventral body surface at rates that were initially similar to aquatic rates. The 3H-H2O flux declined over time but increased upon reimmersion. We conclude that the slender lungfish body surface, including the gills, has relatively low permeability to water and ions but that the ventral surface is an important site of osmoregulation and ionoregulation. We further propose that an amphibian-like combination of ventral skin water and ion permeability, plus internal urea accumulation during air exposure, allows P. dolloi to extract water from its surroundings and to store water in the muscle when the water supply becomes limited

Bacteriophages limit the existence conditions for conjugative plasmids

Bacteriophages are a major cause of bacterial mortality and impose strong selection on natural bacterial populations, yet their effects on the dynamics of conjugative plasmids have rarely been tested. We combined experimental evolution, mathematical modeling, and individual-based simulations to explain how the ecological and population genetics effects of bacteriophages upon bacteria interact to determine the dynamics of conjugative plasmids and their persistence. The ecological effects of bacteriophages on bacteria are predicted to limit the existence conditions for conjugative plasmids, preventing persistence under weak selection for plasmid accessory traits. Experiments showed that phages drove faster extinction of plasmids in environments where the plasmid conferred no benefit, but they also revealed more complex effects of phages on plasmid dynamics under these conditions, specifically, the temporary maintenance of plasmids at fixation followed by rapid loss. We hypothesized that the population genetic effects of bacteriophages, specifically, selection for phage resistance mutations, may have caused this. Further mathematical modeling and individual-based simulations supported our hypothesis, showing that conjugative plasmids may hitchhike with phage resistance mutations in the bacterial chromosome

Draws and Drawbacks of an Oxford Study Abroad Experience

Using qualitative research methodology, we interviewed 23 American students participating in a study abroad program at Oxford University in the U.K. Results showed four primary draws to participating in the study abroad program and two perceived drawbacks. Positively, Oxford’s first appealing dynamic related to the tutorial system and students’ expanded range of options for specialized topics as well as in-depth study. Next, participants highly valued Oxford’s academic rigor, which accompanied the university’s unique approach to education. Third, Oxford’s location in England appealed to our participants. Finally, students reported hopes that future benefits would result from their decisions to attend Oxford and perceived associations with Oxford’s prestige. As participants weighed these benefits of studying at OU, they contrasted the positive dynamics with two major drawbacks: finances and missed U.S. experiences. Nevertheless, our participants unanimously affirmed their respective decisions to study at Oxford and highly recommended the experience to future potential applicants

A Disk Shadow Around the Young Star ASR 41 in NGC 1333

We present images of the young stellar object ASR 41 in the NGC 1333 star forming region at the wavelengths of H_alpha and [SII] and in the I, J, H, and K-bands. ASR 41 has the near-infrared morphology of an edge-on disk object, but appears an order of magnitude larger than typical systems of this kind. We also present detailed models of the scattering and radiative transfer in systems consisting of a young star surrounded by a proto-planetary disk, and the whole system being embedded in either an infalling envelope or a uniform molecular cloud. The best fit to the observed morphology can be achieved with a disk of approx. 200 AU diameter, immersed in a low density cloud. The low cloud density is necessary to stay below the sub-mm flux upper limits and to preserve the shadow cast by the disk via single scattering. The results demonstrate that ASR 41 is probably not inherently different from typical edge-on disk objects, and that its large apparent size is due to the shadow of a much smaller disk being projected into the surrounding dusty molecular material