Positron Annihilation in the Galaxy

The 511 keV line from positron annihilation in the Galaxy was the first γ-ray line detected to originate from outside our solar system. Going into the fifth decade since the discovery, the source of positrons is still unconfirmed and remains one of the enduring mysteries in γ-ray astronomy. With a large flux of ∼10−3 γ/cm2/s, after 15 years in operation INTEGRAL/SPI has detected the 511 keV line at >50σ and has performed high-resolution spectral studies which conclude that Galactic positrons predominantly annihilate at low energies in warm phases of the interstellar medium. The results from imaging are less certain, but show a spatial distribution with a strong concentration in the center of the Galaxy. The observed emission from the Galactic disk has low surface brightness and the scale height is poorly constrained, therefore, the shear number of annihilating positrons in our Galaxy is still not well know. Positrons produced in β+-decay of nucleosynthesis products, such as 26Al, can account for some of the annihilation emission in the disk, but the observed spatial distribution, in particular the excess in the Galactic bulge, remains difficult to explain. Additionally, one of the largest uncertainties in these studies is the unknown distance that positrons propagate before annihilation. In this paper, we will summarize the current knowledge base of Galactic positrons, and discuss how next-generation instruments could finally provide the answers.Non peer reviewedFinal Accepted Versio

The study of metaphor as part of Critical Discourse Analysis

This article discusses how the study of metaphoric and more generally, figurative language use contributes to critical discourse analysis (CDA). It shows how cognitive linguists’ recognition of metaphor as a fundamental means of concept- and argument-building can add to CDA's account of meaning constitution in the social context. It then discusses discrepancies between the early model of conceptual metaphor theory and empirical data and argues that discursive-pragmatic factors as well as sociolinguistic variation have to be taken into account in order to make cognitive analyses more empirically and socially relevant. In conclusion, we sketch a modified cognitive approach informed by Relevance Theory within CDA

MWA rapid follow-up of gravitational wave transients: prospects for detecting prompt radio counterparts

We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim4$ minutes negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim1000\,\text{deg}^2$ at 120\,MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6\% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim5\text{--}22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.Comment: Accepted for publication in PAS

5-Hydroxytryptamine Modulates Migration, Cytokine and Chemokine Release and T-Cell Priming Capacity of Dendritic Cells In Vitro and In Vivo

Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR1 and 5-HTR2 receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR3, 5-HTR4 and 5-HTR7 receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders

Can Echocardiographic Findings Predict Falls in Older Persons?

Background. The European and American guidelines state the need for echocardiography in patients with syncope. 50% of older adults with syncope present with a fall. Nonetheless, up to now no data have been published addressing echocardiographic abnormalities in older fallers. Method and Findings. In order to determine the association between echocardiographic abnormalities and falls in older adults, we performed a prospective cohort study, in which 215 new consecutive referrals (age 77.4 SD 6.0) of a geriatric outpatient clinic of a Dutch university hospital were included. During the previous year, 139 had experienced a fall. At baseline, all patients underwent routine two-dimensional and Doppler echocardiography. Falls were recorded during a three-month follow-up. Multivariate adjustment for compounders was performed with a Cox proportional hazards model. 557 patients (26%) fell at least once during follow-up. The adjusted hazard ratio of a fall during follow-up was 135 (95% Cl, 1.08-1.71) for pulmonary hypertension, 1.66 (95% Cl, 1.01 to 2.89) for 4-initial regurgitation, 2.41 (95% Cl, 1.32 to 4.37) for tricuspid regurgitation and 1.76 (95% Cl, 1.03 to 3.01) for pulmonary regurgitation. For aoitic regurgitation the risk of a fall was also increased, but non-significantly. (hazard ratio, 1.57 [95% Cl 0.85 to 2.92]). Trend analysis of the severity of the difterent regurgitations showed a significant relationship for mitral, tricuspid and pulmonary valve regurgitation and pulmonary hypertension. Conclusions. Echo(Dopler)cardiography can be useful in order to identify risk indicators for falling. Presence of pulmonary hypertension or regurgitation of mitral, tricuspid or pulmonary valves was associated with a higher fall risk. Our study indicates that the diagnostic work-up for falls in older adults might be improved by adding an echo(Doppler)cardiogram in selected groups

P2X7 receptor: Death or life?

The P2X7 plasma membrane receptor is an intriguing molecule that is endowed with the ability to kill cells, as well as to activate many responses and even stimulate proliferation. Here, the authors give an overview on the multiplicity and complexity of P2X7-mediated responses, discussing recent information on this receptor. Particular attention has been paid to early and late signs of apoptosis and necrosis linked to activation of the receptor and to the emerging field of P2X7 function in carcinogenesis

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

P1 receptors and cytokine secretion

Evidence has accumulated in the last three decades to suggest tissue protection and regeneration by adenosine in multiple different cell types. Adenosine produced in hypoxic or inflamed environments reduces tissue injury and promotes repair by receptor-mediated mechanisms. Among other actions, regulation of cytokine production and secretion by immune cells, astrocytes and microglia (the brain immunocytes) has emerged as a main mechanism at the basis of adenosine effects in diseases characterized by a marked inflammatory component. Many recent studies have highlighted that signalling through A1 and A2A adenosine receptors can powerfully prevent the release of pro-inflammatory cytokines, thus inhibiting inflammation and reperfusion injury. However, the activation of adenosine receptors is not invariably protective of tissues, as signalling through the A2B adenosine receptor has been linked to pro-inflammatory actions which are, at least in part, mediated by increased release of pro-inflammatory cytokines from epithelial cells, astrocytes and fibroblasts. Here, we discuss the multiple actions of P1 receptors on cytokine secretion, by analyzing, in particular, the role of the various adenosine receptor subtypes, the complex reciprocal interplay between the adenosine and the cytokine systems, their pathophysiological significance and the potential of adenosine receptor ligands as new anti-inflammatory agents

Population of Merging Compact Binaries Inferred Using Gravitational Waves through GWTC-3

We report on the population properties of compact binary mergers inferred from gravitational-wave observations of these systems during the first three LIGO-Virgo observing runs. The Gravitational-Wave Transient Catalog 3 (GWTC-3) contains signals consistent with three classes of binary mergers: binary black hole, binary neutron star, and neutron star-black hole mergers. We infer the binary neutron star merger rate to be between 10 and 1700 Gpc-3 yr-1 and the neutron star-black hole merger rate to be between 7.8 and 140 Gpc-3 yr-1, assuming a constant rate density in the comoving frame and taking the union of 90% credible intervals for methods used in this work. We infer the binary black hole merger rate, allowing for evolution with redshift, to be between 17.9 and 44 Gpc-3 yr-1 at a fiducial redshift (z=0.2). The rate of binary black hole mergers is observed to increase with redshift at a rate proportional to (1+z)κ with κ=2.9-1.8+1.7 for z≲1. Using both binary neutron star and neutron star-black hole binaries, we obtain a broad, relatively flat neutron star mass distribution extending from 1.2-0.2+0.1 to 2.0-0.3+0.3M⊙. We confidently determine that the merger rate as a function of mass sharply declines after the expected maximum neutron star mass, but cannot yet confirm or rule out the existence of a lower mass gap between neutron stars and black holes. We also find the binary black hole mass distribution has localized over- and underdensities relative to a power-law distribution, with peaks emerging at chirp masses of 8.3-0.5+0.3 and 27.9-1.8+1.9M⊙. While we continue to find that the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above approximately 60M⊙, which would indicate the presence of a upper mass gap. Observed black hole spins are small, with half of spin magnitudes below χi≈0.25. While the majority of spins are preferentially aligned with the orbital angular momentum, we infer evidence of antialigned spins among the binary population. We observe an increase in spin magnitude for systems with more unequal-mass ratio. We also observe evidence of misalignment of spins relative to the orbital angular momentum

The population of merging compact binaries inferred using gravitational waves through GWTC-3

We report on the population properties of 76 compact binary mergers detected with gravitational waves below a false alarm rate of 1 per year through GWTC-3. The catalog contains three classes of binary mergers: BBH, BNS, and NSBH mergers. We infer the BNS merger rate to be between 10 $\rm{Gpc^{-3} yr^{-1}}$ and 1700 $\rm{Gpc^{-3} yr^{-1}}$ and the NSBH merger rate to be between 7.8 $\rm{Gpc^{-3}\, yr^{-1}}$ and 140 $\rm{Gpc^{-3} yr^{-1}}$ , assuming a constant rate density versus comoving volume and taking the union of 90% credible intervals for methods used in this work. Accounting for the BBH merger rate to evolve with redshift, we find the BBH merger rate to be between 17.9 $\rm{Gpc^{-3}\, yr^{-1}}$ and 44 $\rm{Gpc^{-3}\, yr^{-1}}$ at a fiducial redshift (z=0.2). We obtain a broad neutron star mass distribution extending from $1.2^{+0.1}_{-0.2} M_\odot$ to $2.0^{+0.3}_{-0.3} M_\odot$. We can confidently identify a rapid decrease in merger rate versus component mass between neutron star-like masses and black-hole-like masses, but there is no evidence that the merger rate increases again before 10 $M_\odot$. We also find the BBH mass distribution has localized over- and under-densities relative to a power law distribution. While we continue to find the mass distribution of a binary's more massive component strongly decreases as a function of primary mass, we observe no evidence of a strongly suppressed merger rate above $\sim 60 M_\odot$. The rate of BBH mergers is observed to increase with redshift at a rate proportional to $(1+z)^{\kappa}$ with $\kappa = 2.9^{+1.7}_{-1.8}$ for $z\lesssim 1$. Observed black hole spins are small, with half of spin magnitudes below $\chi_i \simeq 0.25$. We observe evidence of negative aligned spins in the population, and an increase in spin magnitude for systems with more unequal mass ratio