Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

On the progenitor of binary neutron star merger GW170817

On 2017 August 17 the merger of two compact objects with masses consistent with two neutron stars was discovered through gravitational-wave (GW170817), gamma-ray (GRB 170817A), and optical (SSS17a/AT 2017gfo) observations. The optical source was associated with the early-type galaxy NGC 4993 at a distance of just ∼40 Mpc, consistent with the gravitational-wave measurement, and the merger was localized to be at a projected distance of ∼2 kpc away from the galaxy's center. We use this minimal set of facts and the mass posteriors of the two neutron stars to derive the first constraints on the progenitor of GW170817 at the time of the second supernova (SN). We generate simulated progenitor populations and follow the three-dimensional kinematic evolution from binary neutron star (BNS) birth to the merger time, accounting for pre-SN galactic motion, for considerably different input distributions of the progenitor mass, pre-SN semimajor axis, and SN-kick velocity. Though not considerably tight, we find these constraints to be comparable to those for Galactic BNS progenitors. The derived constraints are very strongly influenced by the requirement of keeping the binary bound after the second SN and having the merger occur relatively close to the center of the galaxy. These constraints are insensitive to the galaxy's star formation history, provided the stellar populations are older than 1 Gyr

Constraints on cosmic strings using data from the first Advanced LIGO observing run

Cosmic strings are topological defects which can be formed in grand unified theory scale phase transitions in the early universe. They are also predicted to form in the context of string theory. The main mechanism for a network of Nambu-Goto cosmic strings to lose energy is through the production of loops and the subsequent emission of gravitational waves, thus offering an experimental signature for the existence of cosmic strings. Here we report on the analysis conducted to specifically search for gravitational-wave bursts from cosmic string loops in the data of Advanced LIGO 2015-2016 observing run (O1). No evidence of such signals was found in the data, and as a result we set upper limits on the cosmic string parameters for three recent loop distribution models. In this paper, we initially derive constraints on the string tension Gμ and the intercommutation probability, using not only the burst analysis performed on the O1 data set but also results from the previously published LIGO stochastic O1 analysis, pulsar timing arrays, cosmic microwave background and big-bang nucleosynthesis experiments. We show that these data sets are complementary in that they probe gravitational waves produced by cosmic string loops during very different epochs. Finally, we show that the data sets exclude large parts of the parameter space of the three loop distribution models we consider

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

F-fluorodeoxyglucose (FED)-PET-CT diagnosis of medium and large vessels vasculitis in an elderly woman with pyrexia of unknown origin (PUO): case history and cost effectiveness analysis

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Transitioning to resilience and sustainability in urban communities

Adapting to the challenges of rapid urban growth and societal change will require mechanisms for efficient transitioning to an embedded resilience. This has become central to the exploration of methods for achieving truly sustainable urban growth. However, while transitioning and resilience are useful descriptors, they can be abstract or conflicting ideals and their meanings obscured by a lack of concrete examples, both being barriers to many planning objectives. In this paper, we hold a lens over key issues in transitioning to resilience in urban areas by outlining emerging challenges that may offer directions towards operationalising how cities might transition to a more resilient future, while ensuring that communities are at the center of the process. The emerging and challenging areas – geospatial ICT, green infrastructure planning, novel design using collaborative responses, climate planning, limiting urban sprawl and short-circuit economic approaches – are explored as viable facets for devising and sustaining urban transition strategies. We conclude with a discussion on the need for developing a synergistic approach in practice to facilitate transition.European Research CouncilFP7 Grant Agreement 282834 / TURAS ProjectSB. 15/05/201

Baseline health and disease assessment of founder Eastern Quolls (Dasyurus Viverrinus) during a conservation translocation to mainland Australia

We evaluated the health of 31 (eight males, 23 females) founder eastern quolls (Dasyurus viverrinus), translocated to a fenced reserve in the Australian Capital Territory between February 2016 and July 2017. Quolls were wild caught in Tasmania (16 animals) or captive bred at Mount Rothwell Biodiversity Interpretation Centre, Victoria (15 animals). Quolls were assessed for the presence of selected potential pathogens (Toxoplasma gondii, herpesviruses, Salmonella serovars, hemoprotozoa, and ectoparasites). We assessed the relationships among sex, provenance (captive or free ranging), T. gondii or herpesvirus infection, weight, and hematologic and biochemical variables. Six of 21 quolls (29%) tested were seropositive for antibodies to T. gondii. Seropositive quolls weighed significantly more and had significantly lower potassium levels, anion gaps, and urea and triglyceride levels than seronegative quolls had. Eighteen of 31 (58%) combined conjunctival-pharyngeal-cloacal swabs collected from quolls were PCR positive for a newly identified gammaherpesvirus, tentatively named dasyurid gammaherpesvirus 3. There were no significant differences among hematologic and biochemical variables or body weights from PCR-positive and PCR-negative quolls. Eighteen of 18 (100%) of rectal-swab samples were culture negative for Salmonella serovars. Three species of tick (Ixodes tasmani, Ixodes fecialis, and Ixodes holocyclus), two species of mite (Andreacus radfordi, one unidentified), and four species of flea (Pygiopsylla hoplia, Acanthopsylla rothschildi rothschildi, Uropsylla tasmanica, and Stephanocircus dasyuri), were detected on wild-caught quolls, whereas a fifth species of flea, Echidnophaga myremecobii, was detected only on captive-bred quolls. Five of 15 blood samples (33%) were positive for hemoprotozoan DNA via PCR, a novel Hepatozoon species, a novel Theileria species, Theileria paparinii, and Trypanosoma copemani were detected. Despite the presence of several potential pathogens known to be associated with disease in other marsupials, the quolls were considered to be in good general health, suitable for translocation, and a viable population was subsequently established