69 research outputs found
A Remark on the Twin âParadoxâ
The Twin âParadoxâ is investigated using a method that emphasises the symmetry between the twins. All the calculations are performed using the Schwarzschild metric, making the result valid in General Relativity as well in the special case of Minkowski space
On the Time Evolution of some Robinson-Trautman Line Elements
We present a review of some aspects of the linearised Robinson-Trautman metrics, mainly the study of the initial-value problem and a long-term expansion of a special case of these line elements. The problem of wire-singularities is also considered
On the Problem of Space-time Symmetries in the Theory of Supergravity (Part II)
The definition of a space-time symmetry, developed in a previous paper in the framework of Simple (N=1) Supergravity, is extended to the N=2 theory. As an application, the properties of the N=2 plane wave are studied. The mathematically related question of defining the Lie derivative of a spinor is also considered
A Note on Lie-Lorentz Derivatives
The definition of ``Lie derivative'' of spinors with respect to Killing
vectors is extended to all kinds of Lorentz tensors. This Lie-Lorentz
derivative appears naturally in the commutator of two supersymmetry
transformations generated by Killing spinors and vanishes for Vielbeins. It can
be identified as the generator of the action of isometries on supergravity
fields and its use for the calculation of supersymmetry algebras is revised and
extended.Comment: Latex2e, 9 pages, AMS font
The Sun's position in the sky
We express the position of the Sun in the sky as a function of time and the
observer's geographic coordinates. Our method is based on applying rotation
matrices to vectors describing points on the celestial sphere. We also derive
direct expressions, as functions of date of the year and geographic latitude,
for the duration of daylight, the maximum and minimum altitudes of the Sun, and
the cardinal directions to sunrise and sunset. We discuss how to account for
the eccentricity of the earth's orbit, the precessions of the equinoxes and the
perihelion, the size of the solar disk, and atmospheric refraction. We
illustrate these results by computing the dates of "Manhattanhenge" (when
sunset aligns with the east-west streets on the main traffic grid for
Manhattan, in New York City), by plotting the altitude of the Sun over
representative cities as a function of time, and by showing plots ("analemmas")
for the position of the Sun in the sky at a given hour of the day.Comment: 19 pages, 16 figures. v3: Replaced to match published version and to
re-package Mathematica notebook as an ancillary fil
Maxwell's theory on a post-Riemannian spacetime and the equivalence principle
The form of Maxwell's theory is well known in the framework of general
relativity, a fact that is related to the applicability of the principle of
equivalence to electromagnetic phenomena. We pose the question whether this
form changes if torsion and/or nonmetricity fields are allowed for in
spacetime. Starting from the conservation laws of electric charge and magnetic
flux, we recognize that the Maxwell equations themselves remain the same, but
the constitutive law must depend on the metric and, additionally, may depend on
quantities related to torsion and/or nonmetricity. We illustrate our results by
putting an electric charge on top of a spherically symmetric exact solution of
the metric-affine gauge theory of gravity (comprising torsion and
nonmetricity). All this is compared to the recent results of Vandyck.Comment: 9 pages, REVTeX, no figures; minor changes, version to be published
in Class. Quantum Gra
The cost of mitigation revisited
Estimates of economic implications of climate policy are important inputs into policy-making. Despite care to contextualize quantitative assessments of mitigation costs, one strong view outside academic climate economics is that achieving Paris Agreement goals implies sizable macroeconomic losses. Here, we argue that this notion results from unwarranted simplification or omission of the complexities of quantifying mitigation costs, which generates ambiguity in communication and interpretation. We synthesize key factors influencing mitigation cost estimates to guide interpretation of estimates, for example from the Intergovernmental Panel on Climate Change, and suggest ways to improve the underlying models. We propose alternatives for the scenario design framework, the framing of mitigation costs and the methods used to derive them, to better inform public debate and policy
External validation of the Ottawa subarachnoid hemorrhage clinical decision rule in patients with acute headache â
We aim to externally validate the Ottawa subarachnoid hemorrhage (OSAH) clinical decision rule. This rule identifies patients with acute nontraumatic headache who require further investigation. We conducted a medical record review of all patients presenting to the emergency department (ED) with headache from January 2011 to November 2013. Per the OSAH rule, patients with any of the following predictors require further investigation: age 40 years or older, neck pain, stiffness or limited flexion, loss of consciousness, onset during exertion, or thunderclap. The rule was applied following the OSAH rule criteria. Patients were followed up for repeat visits within 7 days of initial presentation. Data were electronically harvested from the electronic medical record and manually abstracted from individual patient charts using a standardized data abstraction form. Calibration between trained reviewers was performed periodically. A total of 5034 ED visits with acute headache were reviewed for eligibility. There were 1521 visits that met exclusion criteria, and 3059 had headache of gradual onset or time to maximal intensity greater than or equal to 1 hour. The rule was applied to 454 patients (9.0%). There were 9 cases of subarachnoid hemorrhage (SAH), yielding an incidence of 2.0% (95% confidence interval [CI], 1.0%-3.9%) in the eligible cohort. The sensitivity for SAH was 100% (95% CI, 62.9%-100%); specificity, 7.6% (95% CI, 5.4%-10.6%); positive predictive value, 2.1% (95% CI 1.0%-4.2%); and negative predictive value, 100% (95% CI, 87.4%-100%). The OSAH rule was 100% sensitive for SAH in the eligible cohort. However, its low specificity and applicability to only a minority of ED patients with headache (9%) reduce its potential impact on practice
Coherent methods in the X-ray sciences
X-ray sources are developing rapidly and their coherent output is growing
extremely rapidly. The increased coherent flux from modern X-ray sources is
being matched with an associated rapid development in experimental methods.
This article reviews the literature describing the ideas that utilise the
increased brilliance from modern X-ray sources. It explores how ideas in
coherent X-ray science are leading to developments in other areas, and vice
versa. The article describes measurements of coherence properties and uses this
discussion as a base from which to describe partially-coherent diffraction and
X-ray phase contrast imaging, with its applications in materials science,
engineering and medicine. Coherent diffraction imaging methods are reviewed
along with associated experiments in materials science. Proposals for
experiments to be performed with the new X-ray free-electron-lasers are briefly
discussed. The literature on X-ray photon correlation spectroscopy is described
and the features it has in common with other coherent X-ray methods are
identified. Many of the ideas used in the coherent X-ray literature have their
origins in the optical and electron communities and these connections are
explored. A review of the areas in which ideas from coherent X-ray methods are
contributing to methods for the neutron, electron and optical communities is
presented.Comment: A review articel accepted by Advances in Physics. 158 pages, 29
figures, 3 table
The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor In Vitro and Confer Resistance To Nirmatrelvir.
The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged in vitro in the presence of increasing concentrations of ALG-097161, a probe compound designed in the context of a 3CLpro drug discovery program. We identified a combination of amino acid substitutions in 3CLpro (L50F E166A L167F) that is associated withâa >20Ă increase in 50% effective concentration (EC50) values for ALG-097161, nirmatrelvir (PF-07321332), PF-00835231, and ensitrelvir. While two of the single substitutions (E166A and L167F) provide low-level resistance to the inhibitors in a biochemical assay, the triple mutant results in the highest levels of resistance (6Ă to 72Ă). All substitutions are associated with a significant loss of enzymatic 3CLpro activity, suggesting a reduction in viral fitness. Structural biology analysis indicates that the different substitutions reduce the number of inhibitor/enzyme interactions while the binding of the substrate is maintained. These observations will be important for the interpretation of resistance development to 3CLpro inhibitors in the clinical setting. IMPORTANCE Paxlovid is the first oral antiviral approved for treatment of SARS-CoV-2 infection. Antiviral treatments are often associated with the development of drug-resistant viruses. In order to guide the use of novel antivirals, it is essential to understand the risk of resistance development and to characterize the associated changes in the viral genes and proteins. In this work, we describe for the first time a pathway that allows SARS-CoV-2 to develop resistance against Paxlovid in vitro. The characteristics of in vitro antiviral resistance development may be predictive for the clinical situation. Therefore, our work will be important for the management of COVID-19 with Paxlovid and next-generation SARS-CoV-2 3CLpro inhibitors
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