Extended Lifetime in Computational Evolution of Isolated Black Holes

Solving the 4-d Einstein equations as evolution in time requires solving equations of two types: the four elliptic initial data (constraint) equations, followed by the six second order evolution equations. Analytically the constraint equations remain solved under the action of the evolution, and one approach is to simply monitor them ({\it unconstrained} evolution). The problem of the 3-d computational simulation of even a single isolated vacuum black hole has proven to be remarkably difficult. Recently, we have become aware of two publications that describe very long term evolution, at least for single isolated black holes. An essential feature in each of these results is {\it constraint subtraction}. Additionally, each of these approaches is based on what we call "modern," hyperbolic formulations of the Einstein equations. It is generally assumed, based on computational experience, that the use of such modern formulations is essential for long-term black hole stability. We report here on comparable lifetime results based on the much simpler ("traditional") $\dot g$ - $\dot K$ formulation. We have also carried out a series of {\it constrained} 3-d evolutions of single isolated black holes. We find that constraint solution can produce substantially stabilized long-term single hole evolutions. However, we have found that for large domains, neither constraint-subtracted nor constrained $\dot g$ - $\dot K$ evolutions carried out in Cartesian coordinates admit arbitrarily long-lived simulations. The failure appears to arise from features at the inner excision boundary; the behavior does generally improve with resolution.Comment: 20 pages, 6 figure

Public Health Governance and Population Health Outcomes

Research reviews have identified a gap in understanding the diversity of health department governance structures and in understanding how the variations in governing relates to health outcomes. This report details the categorization of local public health governance and reveals that certain governance types may be better suited to achieve better population health outcomes. State systems achieve the poorest health outcomes, but the best health outcomes are achieved when the political branches have a key role in local public health governance. Public health systems should consider greater local control and involvement in governance; but local governance should include the political branches -- and even the state -- to achieve more positive health outcomes

Characterizing the Dust Coma of Comet C/2012 S1 (ISON) at 4.15 AU from the Sun

We report results from broadband visible images of comet C/2012 S1 (ISON) obtained with the Hubble Space Telescope Wide Field Camera 3 on 2013 April 10. C/ISON's coma brightness follows a 1/{\rho} (where {\rho} is the projected distance from the nucleus) profile out to 5000 km, consistent with a constant speed dust outflow model. The turnaround distance in the sunward direction suggests that the dust coma is composed of sub-micron-sized particles emitted at speeds of tens of meters s$^{-1}$. A({\theta})f{\rho}, which is commonly used to characterize the dust production rate, was 1340 and 1240 cm in the F606W and F438W filters, respectively, in apertures <1.6" in radius. The dust colors are slightly redder than solar, with a slope of 5.0$\pm$0.2% per 100 nm, increasing to >10% per 100 nm 10,000 km down the tail. The colors are similar to those of comet C/1995 O1 (Hale-Bopp) and other long-period comets, but somewhat bluer than typical values for short-period comets. The spatial color variations are also reminiscent of C/Hale-Bopp. A sunward jet is visible in enhanced images, curving to the north and then tailward in the outer coma. The 1.6"-long jet is centered at a position angle of 291$^\circ$, with an opening angle of about 45$^\circ$. The jet morphology remains unchanged over 19 hours of our observations, suggesting that it is near the rotational pole of the nucleus, and implying that the pole points to within 30 deg of (RA, Dec) = (330$^\circ$, 0$^\circ$). This pole orientation indicates a high obliquity of 50$^\circ$-80$^\circ$

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing

Near-Infrared and Optical Observations of Type Ic SN 2021krf: Luminous Late-time Emission and Dust Formation

We present near-infrared (NIR) and optical observations of the Type Ic supernova (SN Ic) SN 2021krf obtained between days 13 and 259 at several ground-based telescopes. The NIR spectrum at day 68 exhibits a rising $K$-band continuum flux density longward of $\sim$ 2.0 $\mu$m, and a late-time optical spectrum at day 259 shows strong [O I] 6300 and 6364 \r{A} emission-line asymmetry, both indicating the presence of dust, likely formed in the SN ejecta. We estimate a carbon-grain dust mass of $\sim$ 2 $\times$ 10$^{-5}$ M$_{\odot}$ and a dust temperature of $\sim$ 900 - 1200 K associated with this rising continuum and suggest the dust has formed in SN ejecta. Utilizing the one-dimensional multigroup radiation hydrodynamics code STELLA, we present two degenerate progenitor solutions for SN 2021krf, characterized by C-O star masses of 3.93 and 5.74 M$_{\odot}$, but with the same best-fit $^{56}$Ni mass of 0.11 M$_{\odot}$ for early times (0-70 days). At late times (70-300 days), optical light curves of SN 2021krf decline substantially more slowly than that expected from $^{56}$Co radioactive decay. Lack of H and He lines in the late-time SN spectrum suggests the absence of significant interaction of the ejecta with the circumstellar medium. We reproduce the entire bolometric light curve with a combination of radioactive decay and an additional powering source in the form of a central engine of a millisecond pulsar with a magnetic field smaller than that of a typical magnetar.Comment: Accepted for publication in ApJ, 27 pages, 21 figures, 6 tables. Previous arXiv submission (arXiv:2211.00205) replaced after acceptanc

Foot-and-mouth disease virus 2C is a hexameric AAA+ protein with a coordinated ATP hydrolysis mechanism.

Foot-and-mouth disease virus (FMDV), a positive sense, single-stranded RNA virus, causes a highly contagious disease in cloven-hoofed livestock. Like other picornaviruses, FMDV has a conserved 2C protein assigned to the superfamily 3 helicases a group of AAA+ ATPases that has a predicted N-terminal membrane-binding amphipathic helix attached to the main ATPase domain. In infected cells, 2C is involved in the formation of membrane vesicles, where it co-localizes with viral RNA replication complexes, but its precise role in virus replication has not been elucidated. We show here that deletion of the predicted N-terminal amphipathic helix enables overexpression in Escherichia coli of a highly soluble truncated protein, 2C(34–318), that has ATPase and RNA binding activity. ATPase activity was abrogated by point mutations in the Walker A (K116A) and B (D160A) motifs and Motif C (N207A) in the active site. Unliganded 2C(34–318) exhibits concentration-dependent self-association to yield oligomeric forms, the largest of which is tetrameric. Strikingly, in the presence of ATP and RNA, FMDV 2C(34–318) containing the N207A mutation, which binds but does not hydrolyze ATP, was found to oligomerize specifically into hexamers. Visualization of FMDV 2C-ATP-RNA complexes by negative stain electron microscopy revealed hexameric ring structures with 6-fold symmetry that are characteristic of AAA+ ATPases. ATPase assays performed by mixing purified active and inactive 2C(34–318) subunits revealed a coordinated mechanism of ATP hydrolysis. Our results provide new insights into the structure and mechanism of picornavirus 2C proteins that will facilitate new investigations of their roles in infection

A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science

The Immunological Synapse: a Dynamic Platform for Local Signaling

The immunological synapse (IS) as a concept has evolved from a static view of the junction between T cells and their antigen-presenting cell partners. The entire process of IS formation and extinction is now known to entail a dynamic reorganization of membrane domains and proteins within and adjacent to those domains. Discussion The entire process is also intricately tied to the motility machinery—both as that machinery directs “scanning” prior to T-cell receptor engagement and as it is appropriated during the ongoing developments at the IS. While the synapse often remains dynamic in order to encourage surveillance of new antigen-presenting surfaces, cytoskeletal forces also regulate the development of signals, likely including the assembly of ion channels. In both neuronal and immunological synapses, localized Ca 2+ signals and accumulation or depletion of ions in microdomains accompany the concentration of signaling molecules in the synapse. Such spatiotemporal signaling in the synapse greatly accelerates kinetics and provides essential checkpoints to validate effective cell–cell communication