The geometry of a naked singularity created by standing waves near a Schwarzschild horizon, and its application to the binary black hole problem

The most promising way to compute the gravitational waves emitted by binary black holes (BBHs) in their last dozen orbits, where post-Newtonian techniques fail, is a quasistationary approximation introduced by Detweiler and being pursued by Price and others. In this approximation the outgoing gravitational waves at infinity and downgoing gravitational waves at the holes' horizons are replaced by standing waves so as to guarantee that the spacetime has a helical Killing vector field. Because the horizon generators will not, in general, be tidally locked to the holes' orbital motion, the standing waves will destroy the horizons, converting the black holes into naked singularities that resemble black holes down to near the horizon radius. This paper uses a spherically symmetric, scalar-field model problem to explore in detail the following BBH issues: (i) The destruction of a horizon by the standing waves. (ii) The accuracy with which the resulting naked singularity resembles a black hole. (iii) The conversion of the standing-wave spacetime (with a destroyed horizon) into a spacetime with downgoing waves by the addition of a ``radiation-reaction field''. (iv) The accuracy with which the resulting downgoing waves agree with the downgoing waves of a true black-hole spacetime (with horizon). The model problem used to study these issues consists of a Schwarzschild black hole endowed with spherical standing waves of a scalar field. It is found that the spacetime metric of the singular, standing-wave spacetime, and its radiation-reaction-field-constructed downgoing waves are quite close to those for a Schwarzschild black hole with downgoing waves -- sufficiently close to make the BBH quasistationary approximation look promising for non-tidally-locked black holes.Comment: 12 pages, 6 figure

The efficient packaging of Venezuelan equine encephalitis virus-specific RNAs into viral particles is determined by nsP1–3 synthesis

AbstractAlphaviruses are regarded as attractive systems for expression of heterologous genes and development of recombinant vaccines. Venezuelan equine encephalitis virus (VEE)-based vectors are particularly promising because of their specificity to lymphoid tissues and strong resistance to interferon. To improve understanding of the VEE genome packaging and optimize application of this virus as a vector, we analyzed in more detail the mechanism of packaging of the VEE-specific RNAs. The presence of the RNAs in the VEE particles during serial passaging in tissue culture was found to depend not only on the presence of packaging signal(s), but also on the ability of these RNAs to express in cis nsP1, nsP2 and nsP3 in the form of a P123 precursor. Packaging of VEE genomes into infectious virions was also found to be more efficient compared to that of Sindbis virus, in spite of lower levels of RNA replication and structural protein production

Comment on “Photodetachment in combined static and dynamic electric fields”`

The theoretical analysis of C. Rangan and A. R. P. Rau [Phys. Rev. A 61, 033405 (2000)] on the process of photodetachment of H- in a strong static electric field, which calls into question the predictions of B. Gao and A. F. Starace [Phys. Rev. A 42, 5580 (1990)] and also of M. Q. Bao et al. [Phys. Rev. A 58, 411 (1998)], is shown in this Comment to be incorrect. First, we point out that a number of assumptions of Rangan and Rau’s analysis rest on tenuous theoretical grounds. Second, we adduce two completely independent and different analyses of the problem which precisely confirm the results of Gao and Starace. These independent analyses also provide the interpretation that Gao and Starace’s predicted strong-field effects are due to the exact account of the influence of the static electric field, not only on the final state of the detached electron, but also on the initial bound-electron state

H-1, C-13 and N-15 resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the H-1, C-13 and N-15 resonance backbone assignment as well as the C beta of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions

All Domains of SARS-CoV-2 nsp1 Determine Translational Shutoff and Cytotoxicity of the Protein

The nsp1 of SARS-CoV-2 is a multifunctional protein that modifies the intracellular environment for the needs of viral replication. It is responsible for the development of translational shutoff, and its expression alone is sufficient to cause a cytopathic effect (CPE).Replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strongly affects cellular metabolism and results in rapid development of the cytopathic effect (CPE). The hallmarks of virus-induced modifications are inhibition of translation of cellular mRNAs and redirection of the cellular translational machinery to the synthesis of virus-specific proteins. The multifunctional nonstructural protein 1 (nsp1) of SARS-CoV-2 is a major virulence factor and a key contributor to the development of translational shutoff. In this study, we applied a wide range of virological and structural approaches to further analyze nsp1 functions. The expression of this protein alone was found to be sufficient to cause CPE. However, we selected several nsp1 mutants exhibiting noncytopathic phenotypes. The attenuating mutations were detected in three clusters, located in the C-terminal helices, in one of the loops of the structured domain and in the junction of the disordered and structured fragment of nsp1. NMR-based analysis of the wild type nsp1 and its mutants did not confirm the existence of a stable beta 5-strand that was proposed by the X-ray structure. In solution, this protein appears to be present in a dynamic conformation, which is required for its functions in CPE development and viral replication. The NMR data also suggest a dynamic interaction between the N-terminal and C-terminal domains. The identified nsp1 mutations make this protein noncytotoxic and incapable of inducing translational shutoff, but they do not result in deleterious effects on viral cytopathogenicity.IMPORTANCE The nsp1 of SARS-CoV-2 is a multifunctional protein that modifies the intracellular environment for the needs of viral replication. It is responsible for the development of translational shutoff, and its expression alone is sufficient to cause a cytopathic effect (CPE). In this study, we selected a wide range of nsp1 mutants exhibiting noncytopathic phenotypes. The attenuating mutations, clustered in three different fragments of nsp1, were extensively characterized via virological and structural methods. Our data strongly suggest interactions between the nsp1 domains, which are required for the protein's functions in CPE development. Most of the mutations made nsp1 noncytotoxic and incapable of inducing translational shutoff. Most of them did not affect the viability of the viruses, but they did decrease the rates of replication in cells competent in type I IFN induction and signaling. These mutations, and their combinations, in particular, can be used for the development of SARS-CoV-2 variants with attenuated phenotypes

IFIT1 differentially interferes with translation and replication of alphavirus genomes and promotes induction of type I interferon

Alphaviruses are a group of widely distributed human and animal pathogens. It is well established that their replication is sensitive to type I IFN treatment, but the mechanism of IFN inhibitory function remains poorly understood. Using a new experimental system, we demonstrate that in the presence of IFN-β, activation of interferon-stimulated genes (ISGs) does not interfere with either attachment of alphavirus virions to the cells, or their entry and nucleocapsid disassembly. However, it strongly affects translation of the virion-delivered virus-specific RNAs. One of the ISG products, IFIT1 protein, plays a major role in this translation block, although an IFIT1-independent mechanism is also involved. The 5'UTRs of the alphavirus genomes were found to differ significantly in their ability to drive translation in the presence of increased concentration of IFIT1. Prior studies have shown that adaptation of naturally circulating alphaviruses to replication in tissue culture results in accumulation of mutations in the 5'UTR, which increase the efficiency of the promoter located in the 5'end of the genome. Here, we show that these mutations also decrease resistance of viral RNA to IFIT1-induced translation inhibition. In the presence of higher levels of IFIT1, alphaviruses with wt 5'UTRs became potent inducers of type I IFN, suggesting a new mechanism of type I IFN induction. We applied this knowledge of IFIT1 interaction with alphaviruses to develop new attenuated variants of Venezuelan equine encephalitis and chikungunya viruses that are more sensitive to the antiviral effects of IFIT1, and thus could serve as novel vaccine candidates

Influence of chronic obstructive pulmonary disease on hospital outcomes of percutaneous coronary interventions in patients with acute coronary syndrome

Aim. To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS). Materials and methods. A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019–2020 were included, 418 (67%) – men, 208 (33%) – women. Median age – 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO – in 59 (9%) patients (criteria: blood flow 3 grade according to TIMI flow grade; perfusion 2 points according to Myocardial blush grade; ST segment resolution 70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (17 points). Groups were compared on unbalanced data (÷2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel “weighting” method, logistic regression analysis was carried out using “weighting” coefficients. Results as odds ratio (OR) and 95% confidence interval. Results. The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16–11.12); p=0.03; OR CMVO 0.65 (0.35–1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09–13.74); p=0.04; OR CMVO 0.61 (0.31–1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27–68.84); p=0.004; OR CMVO 0.63 (0.30–1.33); p=0.22. Conclusion. The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO

Utilization of an Eilat Virus-Based Chimera for Serological Detection of Chikungunya Infection.

In December of 2013, chikungunya virus (CHIKV), an alphavirus in the family Togaviridae, was introduced to the island of Saint Martin in the Caribbean, resulting in the first autochthonous cases reported in the Americas. As of January 2015, local and imported CHIKV has been reported in 50 American countries with over 1.1 million suspected cases. CHIKV causes a severe arthralgic disease for which there are no approved vaccines or therapeutics. Furthermore, the lack of a commercially available, sensitive, and affordable diagnostic assay limits surveillance and control efforts. To address this issue, we utilized an insect-specific alphavirus, Eilat virus (EILV), to develop a diagnostic antigen that does not require biosafety containment facilities to produce. We demonstrated that EILV/CHIKV replicates to high titers in insect cells and can be applied directly in enzyme-linked immunosorbent assays without inactivation, resulting in highly sensitive detection of recent and past CHIKV infection, and outperforming traditional antigen preparations