On the progressive hardening of the cosmic-ray proton spectrum in the inner Galaxy

Spatial variations of the average properties that characterize the hadronic component of the diffuse Galactic cosmic-ray sea, in particular the spectral slope and normalization, may unveil critical information about their confinement mechanism in the Galaxy. In the first part of this paper we perform an analysis of the Fermi-LAT gamma-ray data with the SkyFACT package, which combines image reconstruction techniques with standard template fitting, isolate the hadronic emission and decompose it into Galactocentric rings. We find a significant hardening of the hadronic spectral index towards the molecular ring. We study this hardening in different energy ranges, and assess its resilience with respect to different prescriptions in the analysis setup. In the second part we quantify the contribution to the diffuse gamma-ray flux coming from unresolved point sources with a dedicated Monte Carlo simulation, and consider whether the trend characterized in the first part can be mimicked by a progressively more relevant flux associated to this component in the inner Galaxy. We find that the observed hardening of the hadronic spectral index cannot be due to unresolved sources in the sub-TeV energy range, especially outside the molecular ring, given reasonable assumptions about the unresolved source population.Comment: 23 pages, 12 figure

Multiwavelength Analysis of Dark Matter Annihilation and RX-DMFIT

Dark matter (DM) particles are predicted by several well motivated models to yield Standard Model particles through self-annihilation that can potentially be detected by astrophysical observations. In particular, the production of charged particles from DM annihilation in astrophysical systems that contain magnetic fields yields radio emission through synchrotron radiation and X-ray emission through inverse Compton scattering of ambient photons. We introduce RX-DMFIT, a tool used for calculating the expected secondary emission from DM annihilation. RX-DMFIT includes a wide range of customizable astrophysical and particle parameters and incorporates important astrophysics including the diffusion of charged particles, relevant radiative energy losses, and magnetic field modelling. We demonstrate the use and versatility of RX-DMFIT by analyzing the potential radio and X-ray signals for a variety of DM particle models and astrophysical environments including galaxy clusters, dwarf spheroidal galaxies and normal galaxies. We then apply RX-DMFIT to a concrete example using Segue I radio data to place constraints for a range of assumed DM annihilation channels. For WIMP models with $M_{\chi} \leq 100$ GeV and assuming weak diffusion, we find that the the leptonic $\mu^+\mu^-$ and $\tau^+\tau^-$ final states provide the strongest constraints, placing limits on the DM particle cross-section well below the thermal relic cross-section, while even for the $b\bar{b}$ channel we find limits close to the thermal relic cross-section. Our analysis shows that radio emission provides a highly competitive avenue for dark matter searches.Comment: 21 pages, 9 figures, 2 tables, corrections to figures, additional text, accepted to JCA

Synchrotron Emission from Dark Matter Annihilation: Predictions for Constraints from Non-detections of Galaxy Clusters with New Radio Surveys

The annihilation of dark matter particles is expected to yield a broad radiation spectrum via the production of Standard Model particles in astrophysical environments. In particular, electrons and positrons from dark matter annihilation produce synchrotron radiation in the presence of magnetic fields. Galaxy clusters are the most massive collapsed structures in the universe, and are known to host $\sim\mu$G-scale magnetic fields. They are therefore ideal targets to search for, or to constrain the synchrotron signal from dark matter annihilation. In this work we use the expected sensitivities of several planned surveys from the next generation of radio telescopes to predict the constraints on dark matter annihilation models which will be achieved in the case of non-detections of diffuse radio emission from galaxy clusters. Specifically, we consider the Tier 1 survey planned for the Low Frequency Array (LOFAR) at 120 MHz, the EMU survey planned for the Australian Square Kilometre Array Pathfinder (ASKAP) at 1.4 GHz, and planned surveys for APERTIF at 1.4 GHz. We find that, for massive clusters and dark matter masses $\lesssim 100$ GeV, the predicted limits on the annihilation cross section would rule out vanilla thermal relic models for even the shallow LOFAR Tier 1, ASKAP, and APERTIF surveys.Comment: accepted to ApJ; removal of LOFAR Tier 2 limits; other minor text changes; conclusions largely unchange

Tiludronate in the horse : pharmacology and therapeutic effects

Hältor och ledskador är inom hästvärlden vanliga problem av stor betydelse som ofta är svåra att behandla. Exempel på skador inom de här kategorierna är spatt och strålbenshälta. På senare år har bisfosfonaten tiludronsyra börjat användas mot dessa åkommor för att hämma benresorptionen. Substansen finns som godkänt läkemedel till häst i ett antal europeiska länder men finns endast tillgängligt som licensläkemedel i Sverige. Syftet med denna litteraturstudie är att redogöra för tiludronsyras verkningsmekanismer, effektivitet och säkerhet. I kroppen binder tiludronsyra till hydroxyapatit som är en beståndsdel i kroppens benmineral. Substansen verkar genom att hämma benresorptionen på olika sätt. In vitro kan tiludronsyra metaboliseras till ATP-analoger i osteoklaster vilket leder till apoptos hos cellerna. Substansen har även visats hämma protonpumpar i osteoklasternas membran vilket gör att nedbrytningen av benmineral minskar. Ett tredje sätt för tiludronsyra att verka mot benresorptionen in vitro är genom förstörelse av aktinringar i osteoklasterna. Det medför att osteoklasternas kontakt med benvävnaden försvagas. Utöver hämningen av benresorptionen har tiludronsyra observerats ha en viss antiinflammatorisk effekt. Substansen verkar då genom att hämma cytokiner och kvävemonoxid (NO). Effekt på metalloproteinaser har också setts. Tiludronsyras effektivitet hos häst är oklar. Studier har visat att tiludronsyra eventuellt kan förbättra skador som spatt, strålbenshälta och lesioner i vertebralkanalen. Bland annat har minskad hältgrad och ökad flexion i ryggraden observerats efter behandling. Studier tyder också på att behandling med tiludronsyra är effektivare mot skador av lindrigare grad. CTX-1, en biomarkör för benresorption, har påvisats minska efter behandling med tiludronsyra till häst. Få studier berör tiludronsyras säkerhet hos häst. Bieffekter som setts är hypokalcemi, ökad hjärtfrekvens, muskeltremor, svettningar och kolik. Dock gavs endast normaldosen av tiludronsyra i den säkerhetsstudie som gjorts och mer långsiktiga studier saknas. Av de studier som utförts för att utreda tiludronsyras effektivitet hos häst har många finansierats av läkemedelsföretaget CEVA som framställer läkemedlet Tildren vilket kan innebära partiskhet. Även metoder för att bedöma tiludronsyras effektivitet kan utgöra bias. Hältbedömning varierar mellan olika personer och koncentrationen av en biomarkör är inte ett mått på benresorptionen i helhet. Delar av studierna har inte varit placebokontrollerade vilket gör det svårt att dra några egentliga slutsatser. För att få en reell bild av tiludronsyras effektivitet samt säkerhet vid olika led- och skelettlidanden behövs det fler oberoende och placebokontrollerade studier med större studiepopulationer.Lameness and joint injuries in horses are frequently occurring and often refractory problems of big importance. Bone spavin and navicular disease are examples. In recent years the bisphosphonate tiludronate has been used as a treatment for these injuries and this substance acts by inhibiting the bone resorption. Tiludronate is an approved drug in several European countries but in Sweden it is only available off-label. The purpose of this study is to review on the mechanisms of actions, the efficacy and the safety of tiludronate. In the body, tiludronate bind to hydroxyapatite in the bone mineral. After binding, it acts by inhibiting the bone resorption in different ways. In vitro, tiludronate can be metabolized into ATP analogues in osteoclasts, which causes apoptosis in the cells. It has also been shown that the substance can inhibit proton pumps in the membranes of the osteoclasts. This decreases the breakdown of bone mineral. A third mechanism which inhibits the bone resorption in vitro is destruction of actin rings in the osteoclasts. This leads to a weaker contact between the osteoclasts and the bone tissue. In addition to inhibited bone resorption, tiludronate has been observed to have an anti-inflammatory effect in vitro. This effect is carried out by inhibiting cytokines and nitrogenmonoxide (NO). An effect on metalloproteinases has also been noticed. The efficacy of tiludronate is not completely clear. Studies have shown that tiludronate may improve injuries like bone spavin, navicular disease and lesions in the vertebral column. Reduced grade of lameness and increased flexion in the spine are examples of effects observed after tiludronate treatment. Studies also indicate that treatment with tiludronate is more effective against less serious injuries. CTX-1, a biomarker of bone resorption, has been shown to decrease after administration of tiludronate in horse. Few studies shine light on the safety of tiludronate in horses. Observed side effects are hypocalcaemia, increased heart rate, muscle tremors, sweating and colic symptoms. In horses, the single safety study that has been done only used normal doses of tiludronate and no longterm studies have been conducted. Many studies on the efficacy of tiludronate in the horse are financed by the drug company CEVA who produce the drug Tildren. This conflict of interest may result in studies with bias and there is also a risk that important information, or negative results, are left out. Methods for assessing the efficacy of tiludronate might also be a source of bias. Assessment of lameness varies between different people and the concentration of a biomarker is not a measure of the bone resorption in its entirety. Parts of the studies on tiludronate have not been controlled with placebo, which makes it hard to draw reliable conclusions. More independent and placebo controlled studies with bigger study populations are therefore needed. This would help in gaining a more representative picture of the comprehensive efficacy of tiludronate and of the safety during treatment of different skeletal and joint injuries

A Radio and X-ray Study of the Merging Cluster A2319

A2319 is a massive, merging galaxy cluster with a previously detected radio halo that roughly follows the X-ray emitting gas. We present the results from recent observations of A2319 at 20 cm with the Jansky Very Large Array (VLA) and a re-analysis of the X-ray observations from XMM-Newton, to investigate the interactions between the thermal and nonthermal components of the ICM . We confirm previous reports of an X-ray cold front, and report on the discovery of a distinct core to the radio halo, 800 kpc in extent, that is strikingly similar in morphology to the X-ray emission, and drops sharply in brightness at the cold front. We detect additional radio emission trailing off from the core, which blends smoothly into the 2 Mpc halo detected with the Green Bank Telescope (GBT; Farnsworth et al., 2013). We speculate on the possible mechanisms for such a two-component radio halo, with sloshing playing a dominant role in the core. By directly comparing the X-ray and radio emission, we find that a hadronic origin for the cosmic ray electrons responsible for the radio halo would require a magnetic field and/or cosmic ray proton distribution that increases with radial distance from the cluster center, and is therefore disfavored.Comment: 9 pages, 5 figures. Submitted to MNRA

Development of a digital twin for real-time simulation of a combustion engine-based power plant with battery storage and grid coupling

Coordinated control of combustion engine-based power plants with battery storage is the next big thing for optimising renewable energy. Digital twins can enable such sophisticated control but currently are too simplistic for the required insight. This study explores the feasibility of a fully physics-based combustion engine model in real-time co-simulation with an electrical power plant model, including battery storage. A detailed, crank-angle resolved, one-dimensional model of a large-bore stationary engine is reduced to a fast-running model (FRM). This engine digital twin is coupled with a complete power plant control model, developed in Simulink. Real-time functions are tested on a dedicated rapid-prototyping system using a target computer. Measurement data from the corresponding power plant infrastructure provide validation for the digital twin. The model-in-the-loop simulations show real-time results from both the standalone combustion and electric submodels mostly within 5% of measured values. The model coupling for fully predictive simulation was tested on a desktop computer, showing expected functionality and validity within 4% and 8% of the respective measured generator and converter outputs. However, execution time of the FRM needs reducing when moving to final hardware-in-the-loop implementation of a complete power plant model.© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Toward a digital twin of a mid-speed marine engine : From detailed 1D engine model to real-time implementation on a target platform

System complexity is challenging for development of marine mid-speed engines when striving to meet increasingly stringent emission targets. Control-oriented modeling offers a solution, cutting calibration time and enabling robust control strategies. Simultaneously, real-time, physics-based engine models (digital twins) are emerging as they offer better predictive capability and scalability than typical mean-value, data-driven approaches. This study explored development of a control-oriented digital twin of a Wärtsilä 4L20 marine engine. Starting from a detailed one-dimensional model (GT-Suite), it explored reduction strategies toward a fast-running engine model (FRM), balancing the calculation speed and accuracy trade-off. Finally, the FRM was tested for real-time implementation on a target machine. Comprehensive experimental data from the 4L20 platform in the VEBIC Engine Laboratory provided the baseline for model calibration. Model calibration and validation covered four representative operating points and involved correlation of crank-angle, resolved in-cylinder pressures, thermal state at several locations of the engine air-path and relevant performance indicators. The results shed new light on the feasibility of digital twins in the marine engine domain. The obtained FRM was three times faster than real-time, while the accuracy loss was comfortably within the 5% tolerance levels for the governing outputs, including crank angle resolved in-cylinder pressure. The grid-resolved simulation was obtained with four times fewer flow components and internal discretization length of 100% and 150% of the cylinder bore for intake and exhaust components respectively. The balance between predictivity, accuracy and real-time surplus, was ultimately more favorable than in state of the art automotive applications and enables exploring further coupling with semi-predictive emission sub-models. The real-time capable FRM is considered applicable in hardware-in-the-loop simulation, and this application is scheduled in a follow-up project.©2023 IMechE. Published by Sage Publications. The article is protected by copyright and reuse is restricted to non-commercial and no derivative uses. Users may also download and save a local copy of an article accessed in an institutional repository for the user's personal reference. Article reuse guidelines: sagepub.com/journals-permissions, DOI: 10.1177/14680874221106168 journals.sagepub.com/home/jerfi=vertaisarvioitu|en=peerReviewed

Gamma Rays from Star Formation in Clusters of Galaxies

Star formation in galaxies is observed to be associated with gamma-ray emission. The detection of gamma rays from star-forming galaxies by the Fermi Large Area Telescope (LAT) has allowed the determination of a functional relationship between star formation rate and gamma-ray luminosity (Ackermann et. al. 2012). Since star formation is known to scale with total infrared (8-1000 micrometers) and radio (1.4 GHz) luminosity, the observed infrared and radio emission from a star-forming galaxy can be used to quantitatively infer the galaxy's gamma-ray luminosity. Similarly, star forming galaxies within galaxy clusters allow us to derive lower limits on the gamma-ray emission from clusters, which have not yet been conclusively detected in gamma rays. In this study we apply the relationships between gamma-ray luminosity and radio and IR luminosities derived in Ackermann et. al. 2012 to a sample of galaxy clusters from Ackermann et. al. 2010 in order to place lower limits on the gamma-ray emission associated with star formation in galaxy clusters. We find that several clusters have predicted lower limits on gamma-ray emission that are within an order of magnitude of the upper limits derived in Ackermann et. al. 2010 based on non-detection by Fermi-LAT. Given the current gamma-ray limits, star formation likely plays a significant role in the gamma-ray emission in some clusters, especially those with cool cores. We predict that both Fermi-LAT over the course of its lifetime and the future Cherenkov Telescope Array will be able to detect gamma-ray emission from star-forming galaxies in clusters.Comment: 17 pages, 2 figures, 2 tables. Minor revisions made to match version accepted to Ap

Induced pluripotent stem cell-based disease modeling identifies ligand-induced decay of megalin as a cause of Donnai-Barrow syndrome

Donnai-Barrow syndrome (DBS) is an autosomal-recessive disorder characterized by multiple pathologies including malformation of forebrain and eyes, as well as resorption defects of the kidney proximal tubule. The underlying cause of DBS are mutations in LRP2, encoding the multifunctional endocytic receptor megalin. Here, we identified a unique missense mutation R3192Q of LRP2 in an affected family that may provide novel insights into the molecular causes of receptor dysfunction in the kidney proximal tubule and other tissues affected in DBS. Using patient-derived induced pluripotent stem cell lines we generated neuroepithelial and kidney cell types as models of the disease. Using these cell models, we documented the inability of megalinR3192Q to properly discharge ligand and ligand-induced receptor decay in lysosomes. Thus, mutant receptors are aberrantly targeted to lysosomes for catabolism, essentially depleting megalin in the presence of ligand in this affected family