Self-Similarity in General Relativity \endtitle

The different kinds of self-similarity in general relativity are discussed, with special emphasis on similarity of the ``first'' kind, corresponding to spacetimes admitting a homothetic vector. We then survey the various classes of self-similar solutions to Einstein's field equations and the different mathematical approaches used in studying them. We focus mainly on spatially homogenous and spherically symmetric self-similar solutions, emphasizing their possible roles as asymptotic states for more general models. Perfect fluid spherically symmetric similarity solutions have recently been completely classified, and we discuss various astrophysical and cosmological applications of such solutions. Finally we consider more general types of self-similar models.Comment: TeX document, 53 page

The sounds of science - A symphony for many instruments and voices

Sounds of Science is the first movement of a symphony for many (scientific) instruments and voices, united in celebration of the frontiers of science and intended for a general audience. John Goodenough, the maestro who transformed energy usage and technology through the invention of the lithium-ion battery, opens the programme, reflecting on the ultimate limits of battery technology. This applied theme continues through the subsequent pieces on energy-related topics - the sodium-ion battery and artificial fuels, by Martin Månsson - and the ultimate challenge for 3D printing, the eventual production of life, by Anthony Atala. A passage by Gerianne Alexander follows, contemplating a related issue: How might an artificially produced human being behave? Next comes a consideration of consciousness and free will by Roland Allen and Suzy Lidström. Further voices and new instruments enter as Warwick Bowen, Nicolas Mauranyapin and Lars Madsen discuss whether dynamical processes of single molecules might be observed in their native state. The exploitation of chaos in science and technology, applications of Bose-Einstein condensates and the significance of entropy follow in pieces by Linda Reichl, Ernst Rasel and Roland Allen, respectively. Mikhail Katsnelson and Eugene Koonin then discuss the potential generalisation of thermodynamic concepts in the context of biological evolution. Entering with the music of the cosmos, Philip Yasskin discusses whether we might be able to observe torsion in the geometry of the Universe. The crescendo comes with the crisis of singularities, their nature and whether they can be resolved through quantum effects, in the composition of Alan Coley. The climax is Mario Krenn, Art Melvin and Anton Zeilinger\u27s consideration of how computer code can be autonomously surprising and creative. In a harmonious counterpoint, his \u27Guidelines for considering AIs as coauthors\u27, Roman Yampolskiy concludes that code is not yet able to take responsibility for coauthoring a paper. An interlude summarises a speech by Zdeněk Papoušek. In a subsequent movement, new themes emerge as we seek to comprehend how far we have travelled along the path to understanding, and speculate on where new physics might arise. Who would have imagined, 100 years ago, a global society permeated by smartphones and scientific instruments so sophisticated that genes can be modified and gravitational waves detected

The X-Ray Pulsar XTE J1858+034 Observed with NuSTAR and Fermi/GBM: Spectral and Timing Characterization plus a Cyclotron Line

Accreting X-ray pulsars (XRPs) undergo luminous X-ray outbursts during which the spectral and timing behavior of the neutron star can be studied in detail. We analyze a NuSTAR observation of the XRP XTE J1858+034 during its outburst in 2019. The spectrum is fit with a phenomenological, a semiempirical, and a physical spectral model. A candidate cyclotron line is found at 48 keV, implying a magnetic field of 5.4 × 1012 G at the site of emission. This is also supported by the physical best-fit model. We propose an orbital period of about 81 days based on the visual inspection of the X-ray outburst recurrence time. Based on Fermi/GBM data, the standard disk accretion-torque theory allowed us to infer a distance of 10.9 ± 1.0 kpc. Pulse profiles are single-peaked and show a pulsed fraction that is strongly energy-dependent at least up to 40 keV

Functional Analysis of the Leading Malaria Vaccine Candidate AMA-1 Reveals an Essential Role for the Cytoplasmic Domain in the Invasion Process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies

The fundamental constants and their variation: observational status and theoretical motivations

This article describes the various experimental bounds on the variation of the fundamental constants of nature. After a discussion on the role of fundamental constants, of their definition and link with metrology, the various constraints on the variation of the fine structure constant, the gravitational, weak and strong interactions couplings and the electron to proton mass ratio are reviewed. This review aims (1) to provide the basics of each measurement, (2) to show as clearly as possible why it constrains a given constant and (3) to point out the underlying hypotheses. Such an investigation is of importance to compare the different results, particularly in view of understanding the recent claims of the detections of a variation of the fine structure constant and of the electron to proton mass ratio in quasar absorption spectra. The theoretical models leading to the prediction of such variation are also reviewed, including Kaluza-Klein theories, string theories and other alternative theories and cosmological implications of these results are discussed. The links with the tests of general relativity are emphasized.Comment: 56 pages, l7 figures, submitted to Rev. Mod. Phy

Identification of Rhoptry Trafficking Determinants and Evidence for a Novel Sorting Mechanism in the Malaria Parasite Plasmodium falciparum

The rhoptry of the malaria parasite Plasmodium falciparum is an unusual secretory organelle that is thought to be related to secretory lysosomes in higher eukaryotes. Rhoptries contain an extensive collection of proteins that participate in host cell invasion and in the formation of the parasitophorous vacuole, but little is known about sorting signals required for rhoptry protein targeting. Using green fluorescent protein chimeras and in vitro pull-down assays, we performed an analysis of the signals required for trafficking of the rhoptry protein RAP1. We provide evidence that RAP1 is escorted to the rhoptry via an interaction with the glycosylphosphatidyl inositol-anchored rhoptry protein RAMA. Once within the rhoptry, RAP1 contains distinct signals for localisation within a sub-compartment of the organelle and subsequent transfer to the parasitophorous vacuole after invasion. This is the first detailed description of rhoptry trafficking signals in Plasmodium

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Mapping and linking supply- and demand-side measures in climate-smart agriculture. A review

Climate change and food security are two of humanity’s greatest challenges and are highly interlinked. On the one hand, climate change puts pressure on food security. On the other hand, farming significantly contributes to anthropogenic greenhouse gas emissions. This calls for climate-smart agriculture—agriculture that helps to mitigate and adapt to climate change. Climate-smart agriculture measures are diverse and include emission reductions, sink enhancements, and fossil fuel offsets for mitigation. Adaptation measures include technological advancements, adaptive farming practices, and financial management. Here, we review the potentials and trade-offs of climate-smart agricultural measures by producers and consumers. Our two main findings are as follows: (1) The benefits of measures are often site-dependent and differ according to agricultural practices (e.g., fertilizer use), environmental conditions (e.g., carbon sequestration potential), or the production and consumption of specific products (e.g., rice and meat). (2) Climate-smart agricultural measures on the supply side are likely to be insufficient or ineffective if not accompanied by changes in consumer behavior, as climate-smart agriculture will affect the supply of agricultural commodities and require changes on the demand side in response. Such linkages between demand and supply require simultaneous policy and market incentives. It, therefore, requires interdisciplinary cooperation to meet the twin challenge of climate change and food security. The link to consumer behavior is often neglected in research but regarded as an essential component of climate-smart agriculture. We argue for not solely focusing research and implementation on one-sided measures but designing good, site-specific combinations of both demand- and supply-side measures to use the potential of agriculture more effectively to mitigate and adapt to climate change