A cryogenic liquid-mirror telescope on the moon to study the early universe

We have studied the feasibility and scientific potential of zenith observing liquid mirror telescopes having 20 to 100 m diameters located on the moon. They would carry out deep infrared surveys to study the distant universe and follow up discoveries made with the 6 m James Webb Space Telescope (JWST), with more detailed images and spectroscopic studies. They could detect objects 100 times fainter than JWST, observing the first, high-red shift stars in the early universe and their assembly into galaxies. We explored the scientific opportunities, key technologies and optimum location of such telescopes. We have demonstrated critical technologies. For example, the primary mirror would necessitate a high-reflectivity liquid that does not evaporate in the lunar vacuum and remains liquid at less than 100K: We have made a crucial demonstration by successfully coating an ionic liquid that has negligible vapor pressure. We also successfully experimented with a liquid mirror spinning on a superconducting bearing, as will be needed for the cryogenic, vacuum environment of the telescope. We have investigated issues related to lunar locations, concluding that locations within a few km of a pole are ideal for deep sky cover and long integration times. We have located ridges and crater rims within 0.5 degrees of the North Pole that are illuminated for at least some sun angles during lunar winter, providing power and temperature control. We also have identified potential problems, like lunar dust. Issues raised by our preliminary study demand additional in-depth analyses. These issues must be fully examined as part of a scientific debate we hope to start with the present article.Comment: 35 pages, 11 figures. To appear in Astrophysical Journal June 20 200

Iterative Design and Usability Testing of the iMHere System for Managing Chronic Conditions and Disability

A novel mobile health platform, Interactive Mobile Health and Rehabilitation (iMHere), is being developed to support wellness and self-management among people with chronic disabilities. The iMHere system currently includes a smartphone app with six modules for use by persons with disabilities and a web portal for use by medical and rehabilitation professionals or other support personnel. Our initial clinical research applying use of this system provides insight into the feasibility of employing iMHere in the development of self-management skills in young adults (ages 18-40 years) with spina bifida (Dicianno, Fairman, McCue, Parmanto, Yih, et al., 2015). This article is focused on describing the iterative design of the iMHere system including usability testing of both the app modules and clinician portal. Our pilot population of persons with spina bifida fostered the creation of a system appropriate for people with a wide variety of functional abilities and needs. As a result, the system is appropriate for use by persons with various disabilities and chronic conditions, not only spina bifida. In addition, the diversity of professionals and support personnel involved in the care of persons with spina bifida (SB) also enabled the design and implementation of the iMHere system to meet the needs of an interdisciplinary team of providers who treat various conditions. The iMHere system has the potential to foster communication and collaboration among members of an interdisciplinary healthcare team, including individuals with chronic conditions and disabilities, for client-centered approach to support self-management skills.

Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

An ethical framework for global vaccine allocation

In this article, we propose the Fair Priority Model for COVID-19 vaccine distribution, and emphasize three fundamental values we believe should be considered when distributing a COVID-19 vaccine among countries: Benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern for all individuals. The Priority Model addresses these values by focusing on mitigating three types of harms caused by COVID-19: death and permanent organ damage, indirect health consequences, such as health care system strain and stress, as well as economic destruction. It proposes proceeding in three phases: the first addresses premature death, the second long-term health issues and economic harms, and the third aims to contain viral transmission fully and restore pre-pandemic activity. To those who may deem an ethical framework irrelevant because of the belief that many countries will pursue "vaccine nationalism," we argue such a framework still has broad relevance. Reasonable national partiality would permit countries to focus on vaccine distribution within their borders up until the rate of transmission is below 1, at which point there would not be sufficient vaccine-preventable harm to justify retaining a vaccine. When a government reaches the limit of national partiality, it should release vaccines for other countries. We also argue against two other recent proposals. Distributing a vaccine proportional to a country's population mistakenly assumes that equality requires treating differently situated countries identically. Prioritizing countries according to the number of front-line health care workers, the proportion of the population over 65, and the number of people with comorbidities within each country may exacerbate disadvantage and end up giving the vaccine in large part to wealthy nations

A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis

Background: Studies are required that evaluate real-world outcomes of inhaled aztreonam lysine in patients with cystic fibrosis (CF). Methods: Our treatment-evaluator tool assessed the effectiveness of inhaled aztreonam in routine practice in 117 CF patients across four time periods (6–12 (P2) and 0–6 months (P1) pre-initiation, and 0–6 (T1) and 6–12 months (T2) post-initiation). Outcomes were: changes in %-predicted forced expiratory volume in 1 s (FEV1), body-mass index (BMI), hospitalisation days and intravenous antibiotic usage. Results: Median FEV1% predicted for each 6-month period was 38.9%, 34.6%, 37.1% and 36.5%; median change was − 2.0% between P2 and P1, increasing to + 0.6% (p < 0.001) between P1 and T1. Annualised hospital bed-days was reduced (p = 0.05) post-initiation, as was intravenous antibiotics days (p = 0.001). BMI increased over 6 months post-initiation (p ≤ 0.001). Conclusions: In patients with CF in routine practice, inhaled aztreonam lysine is associated with improved lung function and weight, and reduced hospitalisation and intravenous antibiotic use

Quantum memories at finite temperature

To use quantum systems for technological applications one first needs to preserve their coherence for macroscopic time scales, even at finite temperature. Quantum error correction has made it possible to actively correct errors that affect a quantum memory. An attractive scenario is the construction of passive storage of quantum information with minimal active support. Indeed, passive protection is the basis of robust and scalable classical technology, physically realized in the form of the transistor and the ferromagnetic hard disk. The discovery of an analogous quantum system is a challenging open problem, plagued with a variety of no-go theorems. Several approaches have been devised to overcome these theorems by taking advantage of their loopholes. The state-of-the-art developments in this field are reviewed in an informative and pedagogical way. The main principles of self-correcting quantum memories are given and several milestone examples from the literature of two-, three- and higher-dimensional quantum memories are analyzed

What are the obligations of pharmaceutical companies in a global health emergency?

All parties involved in researching, developing, manufacturing, and distributing COVID-19 vaccines need guidance on their ethical obligations. We focus on pharmaceutical companies' obligations because their capacities to research, develop, manufacture, and distribute vaccines make them uniquely placed for stemming the pandemic. We argue that an ethical approach to COVID-19 vaccine production and distribution should satisfy four uncontroversial principles: optimising vaccine production, including development, testing, and manufacturing; fair distribution; sustainability; and accountability. All parties' obligations should be coordinated and mutually consistent. For instance, companies should not be obligated to provide host countries with additional booster shots at the expense of fulfilling bilateral contracts with countries in which there are surges. Finally, any satisfactory approach should include mechanisms for assurance that all parties are honouring their obligations. This assurance enables countries, pharmaceutical companies, global organisations, and others to verify compliance with the chosen approach and protect ethically compliant stakeholders from being unfairly exploited by unethical behaviour of others

A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation

Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants

Regulation of the Actin Cytoskeleton by an Interaction of IQGAP Related Protein GAPA with Filamin and Cortexillin I

Filamin and Cortexillin are F-actin crosslinking proteins in Dictyostelium discoideum allowing actin filaments to form three-dimensional networks. GAPA, an IQGAP related protein, is required for cytokinesis and localizes to the cleavage furrow during cytokinesis. Here we describe a novel interaction with Filamin which is required for cytokinesis and regulation of the F-actin content. The interaction occurs through the actin binding domain of Filamin and the GRD domain of GAPA. A similar interaction takes place with Cortexillin I. We further report that Filamin associates with Rac1a implying that filamin might act as a scaffold for small GTPases. Filamin and activated Rac associate with GAPA to regulate actin remodelling. Overexpression of filamin and GAPA in the various strains suggests that GAPA regulates the actin cytoskeleton through interaction with Filamin and that it controls cytokinesis through association with Filamin and Cortexillin

Strong constraints on aerosol-cloud interactions from volcanic eruptions.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response