An INTEGRAL/SPI view of reticulum II: Particle dark matter and primordial black holes limits in the MeV range

© 2022 The Author(s) Published by Oxford University Press on behalf of Royal Astronomical Society. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.1093/mnras/stac008Reticulum II (Ret II) is a satellite galaxy of the Milky Way and presents a prime target to investigate the nature of dark matter (DM) because of its high mass-to-light ratio. We evaluate a dedicated INTEGRAL observation campaign data set to obtain $\gamma$-ray fluxes from Ret II and compare those with expectations from DM. Ret II is not detected in the $\gamma$-ray band 25--8000 keV, and we derive a flux limit of $\lesssim 10^{-8}\,\mathrm{erg\,cm^{-2}\,s^{-1}}$. The previously reported 511 keV line is not seen, and we find a flux limit of $\lesssim 1.7 \times 10^{-4}\,\mathrm{ph\,cm^{-2}\,s^{-1}}$. We construct spectral models for primordial black hole (PBH) evaporation and annihilation/decay of particle DM, and subsequent annihilation of positrons produced in these processes. We exclude that the totality of DM in Ret II is made of a monochromatic distribution of PBHs of masses $\lesssim 8 \times 10^{15}\,\mathrm{g}$. Our limits on the velocity-averaged DM annihilation cross section into $e^+e^-$ are $\langle \sigma v \rangle \lesssim 5 \times 10^{-28} \left(m_{\rm DM} / \mathrm{MeV} \right)^{2.5}\,\mathrm{cm^3\,s^{-1}}$. We conclude that analysing isolated targets in the MeV $\gamma$-ray band can set strong bounds on DM properties without multi-year data sets of the entire Milky Way, and encourage follow-up observations of Ret II and other dwarf galaxies.Peer reviewedFinal Accepted Versio

Search for 511 keV Emission in Satellite Galaxies of the Milky Way with INTEGRAL/SPI

Reproduced with permission from Astronomy & Astrophysics. © 2018 ESO.The positron annihilation gamma-ray signal in the Milky Way (MW) shows a puzzling morphology: a very bright bulge and a very low surface-brightness disk. A coherent explanation of the positron origin, propagation through the Galaxy and subsequent annihilation in the interstellar medium has not yet been found. Tentative explanations involve positrons from radioactivity, X-ray binaries, and dark matter (DM). Dwarf satellite galaxies (DSGs) are believed to be DM-dominated and hence promising candidates in the search for 511 keV emission as a result of DM annihilation into electron-positron pairs. The goal of this study is to constrain possible 511 keV gamma-ray signals from 39 DSGs of the MW and to test the annihilating DM scenario. We use the spectrometer SPI on INTEGRAL to extract individual spectra for the studied objects. As the diffuse galactic emission dominates the signal, the large scale morphology of the MW has been modelled accordingly and was included in a maximum likelihood analysis. Alternatively, a distance-weighted stacked spectrum has been determined. Only Reticulum II (Ret II) shows a 3.1 sigma signal. Five other sources show tentative 2 sigma signals. The mass-to-511-keV-luminosity-ratio shows a marginal trend towards higher values for intrinsically brighter objects, opposite to the V band mass-to-light-ratio, which is generally used to uncover DM in DSGs. All derived flux values are above the level implied by a DM interpretation of the MW bulge signal. The signal from Ret II is unlikely to be related to a DM origin alone, otherwise, the MW bulge would be about 100 times brighter than what is seen. Ret II is exceptional considering the DSG sample, and rather points to enhanced recent star formation activity, if its origins are similar to processes in the MW. Understanding this emission may provide further clues regarding the origin of the annihilation emission in the MW.Peer reviewe

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Safety Analyses of the Phase 3 VISION Trial of [177Lu]Lu-PSMA-617 in Patients with Metastatic Castration-resistant Prostate Cancer

Background and objective: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) plus the standard of care (SoC) significantly improved overall survival and radiographic progression-free survival versus SoC alone in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer in the VISION trial. We evaluated the safety of additional cycles of 177Lu-PSMA-617 and the impact of longer observation time for patients receiving 177Lu-PSMA-617 plus SoC.Methods: VISION was an international, open-label study. Patients were randomised 2:1 to receive 177Lu-PSMA-617 plus SoC or SoC alone. The incidence of treatment-emergent adverse events (TEAEs) was assessed in prespecified subgroups of patients who received ≤4 cycles versus 5-6 cycles of treatment and during each cycle of treatment. The TEAE incidence was also adjusted for treatment exposure to calculate the incidence per 100 patient-treatment years of observation. This analysis was performed for the first occurrence of TEAEs.Key findings and limitations: The any-grade TEAE incidence was similar in cycles 1-4 and cycles 5-6. TEAE frequency was similar across all cycles of 177Lu-PSMA-617 treatment. No additional safety concerns were reported for patients who received >4 cycles. The exposure-adjusted safety analysis revealed that the overall TEAE incidence was similar between arms, but distinct trends for different TEAE types were noted and the incidence of events associated with 177Lu-PSMA-617 remained higher in the 177Lu-PSMA-617 arm.Conclusions and clinical implications: Longer exposure to 177Lu-PSMA-617 plus SoC was not associated with a higher toxicity risk, and the extended time for safety observation could account for the higher TEAE incidence in comparison to SoC alone. The findings support a favourable benefit-risk profile for 6 cycles of 177Lu-PSMA-617 in this setting and the use of up to 6 cycles of 177Lu-PSMA-617 in patients who are clinically benefiting from and tolerating this therapy.Patient summary: For patients with metastatic prostate cancer no longer responding to hormone therapy, an increase in the number of cycles of treatment with a radioactive compound called 177Lu-PSMA-617 from four to six had no additional adverse side effects

A Whey Protein Hydrolysate Promotes Insulinotropic Activity in a Clonal Pancreatic β-Cell Line and Enhances Glycemic Function in ob/ob Mice

Whey protein hydrolysates (WPHs) represent novel antidiabetic agents that affect glycemia in animals and humans, but little is known about their insulinotropic effects. The effects of a WPH were analyzed in vitro on acute glucose-induced insulin secretion in pancreatic BRIN-BD11 β cells. WPH permeability across Caco-2 cell monolayers was determined in a 2-tiered intestinal model. WPH effects on insulin resistance were studied in vivo following an 8-wk oral ingestion (100mg/kg body weight) by ob/ob (OB-WPH) and wild-type mice (WT-WPH) compared with vehicle control (OB and WT groups) usinga 2 3 2 factorial design, genotype 3 treatment. BRIN-BD11 cells showed a robust and reproducible dose-dependent insulinotropic effect of WPH (from 0.01 to 5.00 g/L). WPH bioactive constituents were permeable across Caco-2 cell monolayers. In the OB-WPH and WT-WPH groups, WPH administration improved glucose clearance after a glucose challenge (2 g/kg body weight), as indicated by differences in the area under curves (AUCs) (P ≤ 0.05). The basal plasma glucose concentration was not affected by WPH treatment in either genotype. The plasma insulin concentration was lower in the OB-WPH than in the OB group (P ≤ 0.005) but was similar between the WT and WT-WPH groups; the interaction genotype 3 treatment was significant (P ≤ 0.005). Insulin release from pancreatic islets isolated from the OB-WPH group was greater (P ≤ 0.005) than that from the OB group but did not differ between the WT-WPH and WT groups; the interaction genotype 3 treatment was not significant. In conclusion, an 8-wk oral administration of WPH improved blood glucose clearance, reduced hyperinsulinemia, and restored the pancreatic islet capacity to secrete insulin in response to glucosein ob/ob mice. Hence, it may be useful in diabetes management

MASCOT operations on Ryugu - focus on some specific tasks

Hayabusa2 is an asteroid sample return mission operated by the Japanese space agency, JAXA. It was launched in December 2014. In July 2018, the spacecraft has reached the mission target after a 4-year-long cruise. The objective is a C-type primordial asteroid called Ryugu, in search of organic and hydrated minerals that might give essential clues for the solar system formation. The small lander MASCOT (Mobile Asteroid surface SCOuT) carried aboard Hayabusa2 landed on the surface on the 3rd of October 2018 for reliminary in-situ investigations while the probe is aiming to study Ryugu on a global scale and to return samples to Earth. MASCOT was jointly developed by the German Aerospace Centre (DLR) and the Centre National d'Etudes Spatiales (CNES). It is equipped with a sensor suite consisting of four fully-fledged instruments. DLR was responsible for developing the MASCOT lander and ground segment, and was in charge of planning and conducting lander joint operations from MUSC. CNES supplied the hyperspectral IR spectrometer (MicrOmega, IAS Paris), antennae and power system, provided a support to operations and was in charge of the flight dynamics aspects of the mission. The 17 hours of on-asteroid operations exceeded expectations and the overall landing and operations were a huge success. Indeed, the characteristics of the Ryugu asteroid such as the shape and the gravity were known only after arrival of Hayabusa2 in July 2018 and the operating ccontext was very constrained but did not provide from fulfilling the objectives. This paper is a complement to the overall paper on MASCOT landing and first results. It will focus on several operational tasks such as communication and power subsystems assessments as well as flight dynamics computations needed in real time and for postprocessing

Variability in time reproduction: Difference in ADHD combined and inattentive subtypes

Objective: To examine the relationship between time reproduction, performance variability, and sustained attention deficits in children with attention-deficit/hyperactivity disorder (ADHD) combined (ADHD-C) and inattentive (ADHD-I) subtypes, relative to matched controls. Method: Participants (age range 7.1-14.1 years) performed a time reproduction task. A subset of the ADHD group was also tested on the Sustained Attention to Response Test. Absolute discrepancy, accuracy coefficient, and intraindividual variability scores on the time reproduction task were compared across the three groups (ADHD-C: N = 20; ADHD-I: N = 19; controls: N = 44) and correlated with the Sustained Attention to Response Test. Results: First, significantly better performance was observed in matched controls than in children with ADHD on the time reproduction task. Second, there was a significant difference between the two ADHD subtypes in the variability of the size of errors made at high time intervals (36-60 seconds). Third, intraindividual performance variability in the direction (over- versus under-estimations) of time reproductions correlated with sustained attention performance. Conclusions: Children with ADHD varied more in the size and direction of their time reproduction errors than control children. Those with ADHD-C demonstrated more intraindividual variability than did those with ADHD-I in the size of their errors. The data provide support for a relationship between sustained attention and time reproduction. This relationship has previously been inferred from common right-lateralized neural circuitry that is thought to subserve these processes