ALMA Thermal Observations of Europa

We present four daytime thermal images of Europa taken with the Atacama Large Millimeter Array. Together, these images comprise the first spatially resolved thermal dataset with complete coverage of Europa's surface. The resulting brightness temperatures correspond to a frequency of 233 GHz (1.3 mm) and a typical linear resolution of roughly 200 km. At this resolution, the images capture spatially localized thermal variations on the scale of geologic and compositional units. We use a global thermal model of Europa to simulate the ALMA observations in order to investigate the thermal structure visible in the data. Comparisons between the data and model images suggest that the large-scale daytime thermal structure on Europa largely results from bolometric albedo variations across the surface. Using bolometric albedos extrapolated from Voyager measurements, a homogenous model reproduces these patterns well, but localized discrepancies exist. These discrepancies can be largely explained by spatial inhomogeneity of the surface thermal properties. Thus, we use the four ALMA images to create maps of the surface thermal inertia and emissivity at our ALMA wavelength. From these maps, we identify a region of either particularly high thermal inertia or low emissivity near 90 degrees West and 23 degrees North, which appears anomalously cold in two of our images.Comment: 9 pages, 3 figures, accepted for publication in the Astronomical Journa

Evidence for the intense exchange of MazG in marine cyanophages by horizontal gene transfer

Background: S-PM2 is a phage capable of infecting strains of unicellular cyanobacteria belonging to the genus Synechococcus. S-PM2, like other myoviruses infecting marine cyanobacteria, encodes a number of bacterial-like genes. Amongst these genes is one encoding a MazG homologue that is hypothesized to be involved in the adaption of the infected host for production of progeny phage. Methodology/Principal Findings: This study focuses on establishing the occurrence of mazG homologues in other cyanophages isolated from different oceanic locations. Degenerate PCR primers were designed using the mazG gene of S-PM2. The mazG gene was found to be widely distributed and highly conserved among Synechococcus myoviruses and podoviruses from diverse oceanic provinces. Conclusions/Significance: This study provides evidence of a globally connected cyanophage gene pool, the cyanophage mazG gene having a small effective population size indicative of rapid lateral gene transfer despite being present in a substantial fraction of cyanophage. The Prochlorococcus and Synechococcus phage mazG genes do not cluster with the host mazG gene, suggesting that their primary hosts are not the source of the mazG gene

Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that leads to renal failure in the majority of patients. The very first pharmacological treatment, tolvaptan, received Food and Drug Administration approval in 2018 after previous approval in Europe and other countries. However, tolvaptan is moderately effective and may negatively impact a patient's quality of life due to potentially significant side effects. Additional and improved therapies are still urgently needed, and several clinical trials are underway, which are discussed in the companion paper Müller and Benzing (Management of autosomal-dominant polycystic kidney disease-state-of-the-art) Clin Kidney J 2018; 11: i2-i13. Here, we discuss new therapeutic avenues that are currently being investigated at the preclinical stage. We focus on mammalian target of rapamycin and dual kinase inhibitors, compounds that target inflammation and histone deacetylases, RNA-targeted therapeutic strategies, glucosylceramide synthase inhibitors, compounds that affect the metabolism of renal cysts and dietary restriction. We discuss tissue targeting to renal cysts of small molecules via the folate receptor, and of monoclonal antibodies via the polymeric immunoglobulin receptor. A general problem with potential pharmacological approaches is that the many molecular targets that have been implicated in ADPKD are all widely expressed and carry out important functions in many organs and tissues. Because ADPKD is a slowly progressing, chronic disease, it is likely that any therapy will have to continue over years and decades. Therefore, systemically distributed drugs are likely to lead to potentially prohibitive extra-renal side effects during extended treatment. Tissue targeting to renal cysts of such drugs is one potential way around this problem. The use of dietary, instead of pharmacological, interventions is another

"Hey, Can You Add Captions?": The Critical Infrastructuring Practices of Neurodiverse People on TikTok

Accessibility efforts, how we can make the world usable and useful to as many people as possible, have explicitly focused on how we can support and allow for the autonomy and independence of people with disabilities, neurotypes, chronic conditions, and older adults. Despite these efforts, not all technology is designed or implemented to support everyone's needs. Recently, a community-organized push by creators and general users of TikTok urged the platform to add accessibility features, such as closed captioning to user-generated content, allowing more people to use the platform with greater ease. Our work focuses on an understudied population -- people with ADHD and those who experience similar challenges -- exploring the creative practices people from this community engage in, focusing on the kinds of accessibility they create through their creative work. Through an interview study exploring the experiences of creatives on TikTok, we find that creatives engage in critical infrastructuring -- a process of bottom-up (re)design -- to make the platform more accessible despite the challenges the platform presents to them as creators. We present these critical infrastructuring practices through the themes of: creating and augmenting video editing infrastructures and creating and augmenting video captioning infrastructures. We reflect on the introduction of a top-down infrastructure - the implementation of an auto-captioning feature - shifts the critical infrastructure practices of content creators. Through their infrastructuring, creatives revised sociotechnical capabilities of TikTok to support their own needs as well as the broader needs of the TikTok community. We discuss how the routine of infrastructuring accessibility is actually best conceptualized as incidental care work. We further highlight how accessibility is an evolving sociotechnical construct, and forward the concept of contextual accessibility.Comment: To be published in: Proc. ACM Hum.-Comput. Interact. CSCW '2

Alcohol and Substance Abuse in Higher Education: Suggestions for Student Affairs Professionals

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An intracellular signaling hierarchy determines direction of migration in opposing chemotactic gradients

Neutrophils must follow both endogenous and bacterial chemoattractant signals out of the vasculature and through the interstitium to arrive at a site of infection. By necessity, in the setting of multiple chemoattractants, the neutrophils must prioritize, favoring end target chemoattractants (e.g., fMLP and C5a) emanating from the site of infection over intermediary endogenous chemoattractants (e.g., IL-8 and LTB4) encountered en route to sites of infection. In this study, we propose a hierarchical model of two signaling pathways mediating the decision-making process of the neutrophils, which allows end target molecules to dominate over intermediary chemoattractants. In an under agarose assay, neutrophils predominantly migrated toward end target chemoattractants via p38 MAPK, whereas intermediary chemoattractant-induced migration was phosphoinositide 3-kinase (PI3K)/Akt dependent. When faced with competing gradients of end target and intermediary chemoattractants, Akt activation was significantly reduced within neutrophils, and the cells migrated preferentially toward end target chemoattractants even at 1/1,000th that of intermediary chemoattractants. End target molecules did not require chemotactic properties, since the p38 MAPK activator, LPS, also inhibited Akt and prevented migration to intermediary chemoattractants. p38 MAPK inhibitors not only reversed this hierarchy, such that neutrophils migrated preferentially toward intermediary chemoattractants, but also allowed neutrophils to be drawn out of a local end target chemoattractant environment and toward intermediary chemoattractants unexpectedly in an exaggerated (two- to fivefold) fashion. This was entirely related to significantly increased magnitude and duration of Akt activation. Finally, end target chemoattractant responses were predominantly Mac-1 dependent, whereas nondominant chemoattractants used primarily LFA-1. These data provide support for a two pathway signaling model wherein the end target chemoattractants activate p38 MAPK, which inhibits intermediary chemoattractant-induced PI3K/Akt pathway, establishing an intracellular signaling hierarchy

Carotenoid regulation in Myxococcus xanthus

The Gram-negative soil dwelling bacterium Myxococcus xanthus synthesises carotenoids on exposure to UV illumination. These pigments give the colonies a distinctive orange/red colour, as well as affording them valuable protection from high energy species, generated by chemical reactions fuelled by light. Genetic dissection of the regulation of carotenogenesis has allowed elucidation of transduction of the light signal to the carotenogenic machinery within the cell. The key element in the carotenogenic regulon is the genetic switch manifested by CarR and CarQ, CarR is an integral membrane protein (anti-sigma factor) which sequesters CarQ, the sigma factor, to the membrane in the dark. When cells are illuminated the photosensitiser protoporphyrin IX becomes excited, being unstable it transfers its excitation energy to molecular oxygen. This generates the high energy species singlet oxygen, which is capable of causing severe cellular damage. Singlet oxygen interacts with CarR possibly through the mediation of CarF, the net result is the destruction of CarR and the release of the sigma factor CarQ. CarQ then mediates transcription from the carQRS promoter and the crtl promoter. Transcription from the carQRS promoter leads to the generation of more CarQ and CarS, CarS causes de-repression of the crtEBDC operon. The carotenogenic enzymes encoded by crtl and the crtEBDC cluster catalyse the production of carotenoids, which quench the initial signalling molecules singlet oxygen and protoporphyrin IX. CarR levels accumulate and CarQ is once again secured in an inactive state. This provides a nice example of negative feedback. This work investigates the interaction of CarQ with its cognate promoter at carQRS through in vivo and in vitro molecular and genetic techniques. Site directed mutations were assessed in vivo through the use of lacZ transcriptional fusions, this allowed the identification of important regions in the carQRS promoter. The interaction between the carQRS promoter and the divergent gufA promoter was also assessed. In vitro experiments were used to attempt to further characterise individual mutations. The negative feedback loop was assessed in a crtl mutant to define whether crtl was subject to autoregulation. Previously identified genes downstream of crtl were mutated to allow phenotypic analysis and identification of putative roles in carotenogenesis

Multimonth controlled small molecule release from biodegradable thin films

Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer–drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5–2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues.United States. Army Research Office (Contract W911NF-13-D-0001)United States. Air Force (Contract W911NF-07-D-0004