AugerPrime surface detector electronics

Operating since 2004, the Pierre Auger Observatory has led to major advances in our understanding of the ultra-high-energy cosmic rays. The latest findings have revealed new insights that led to the upgrade of the Observatory, with the primary goal of obtaining information on the primary mass of the most energetic cosmic rays on a shower-by-shower basis. In the framework of the upgrade, called AugerPrime, the 1660 water-Cherenkov detectors of the surface array are equipped with plastic scintillators and radio antennas, allowing us to enhance the composition sensitivity. To accommodate new detectors and to increase experimental capabilities, the electronics is also upgraded. This includes better timing with up-to-date GPS receivers, higher sampling frequency, increased dynamic range, and more powerful local processing of the data. In this paper, the design characteristics of the new electronics and the enhanced dynamic range will be described. The manufacturing and test processes will be outlined and the test results will be discussed. The calibration of the SD detector and various performance parameters obtained from the analysis of thefirst commissioning data will also be presented

Constraining models for the origin of ultra-high-energy cosmic rays with a novel combined analysis of arrival directions, spectrum, and composition data measured at the Pierre Auger Observatory

The combined fit of the measured energy spectrum and shower maximum depth distributions of ultra-high-energy cosmic rays is known to constrain the parameters of astrophysical models with homogeneous source distributions. Studies of the distribution of the cosmic-ray arrival directions show a better agreement with models in which a fraction of the flux is non-isotropic and associated with the nearby radio galaxy Centaurus A or with catalogs such as that of starburst galaxies. Here, we present a novel combination of both analyses by a simultaneous fit of arrival directions, energy spectrum, and composition data measured at the Pierre Auger Observatory. The model takes into account a rigidity-dependent magnetic field blurring and an energy-dependent evolution of the catalog contribution shaped by interactions during propagation. We find that a model containing a flux contribution from the starburst galaxy catalog of around 20% at 40 EeV with a magnetic field blurring of around 20° for a rigidity of 10 EV provides a fair simultaneous description of all three observables. The starburst galaxy model is favored with a significance of 4.5σ (considering experimental systematic effects) compared to a reference model with only homogeneously distributed background sources. By investigating a scenario with Centaurus A as a single source in combination with the homogeneous background, we confirm that this region of the sky provides the dominant contribution to the observed anisotropy signal. Models containing a catalog of jetted active galactic nuclei whose flux scales with the γ-ray emission are, however, disfavored as they cannot adequately describe the measured arrival directions

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Motor rehabilitation after stroke: European Stroke Organisation (ESO) consensus-based definition and guiding framework

Purpose: To propose a consensus-based definition and framework for motor rehabilitation after stroke. Methods: An expert European working group reviewed the literature, attaining internal consensus after external feedback. Findings: Motor rehabilitation is defined as a process that engages people with stroke to benefit their motor function, activity capacity and performance in daily life. It is necessary for people with residual motor disability whose goal is to enhance their functioning, independence and participation. Motor rehabilitation operates through learning- and use-dependent mechanisms. The trajectory of motor recovery varies across patients and stages of recovery. Early behavioral restitution of motor function depends on spontaneous biological mechanisms. Further improvements in activities of daily living are achieved by compensations. Motor rehabilitation is guided by regular assessment of motor function and activity using consensus-based measures, including patient-reported outcomes. Results are discussed with the patient and their carers to set personal goals. During motor rehabilitation patients learn to optimize and adapt their motor, sensory and cognitive functioning through appropriately dosed repetitive, goal-oriented, progressive, task- and context-specific training. Motor rehabilitation supports people with stroke to maximize health, well-being and quality of life. The framework describes the International Classification of Functioning, Disability and Health in the context of stroke, describes neurobiological mechanisms of behavioral restitution and compensation, and summarizes recommendations for clinical assessment, prediction tools, and motor interventions with strong recommendations from clinical practice guidelines (2016-2022). Conclusions: This definition and framework may guide clinical educators, inform clinicians on current recommendations and guidelines, and identify gaps in the evidence base

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles

Reactivity and Biological Properties of a Series of Cytotoxic PtI₂(amine)₂ Complexes, Either <i>cis</i> or <i>trans</i> Configured

Six diiodido–diamine platinum­(II) complexes, either <i>cis</i> or <i>trans</i> configured, were prepared, differing only in the nature of the amine ligand (isopropylamine, dimethylamine, or methylamine), and their antiproliferative properties were evaluated against a panel of human tumor cell lines. Both series of complexes manifested pronounced cytotoxic effects, with the <i>trans</i> isomers being, generally, more effective than their <i>cis</i> counterparts. Cell cycle analysis revealed different modes of action for these new Pt­(II) complexes with respect to cisplatin. The reactivity of these platinum compounds with a number of biomolecules, including cytochrome c, two sulfur containing modified amino acids, 9-ethylguanine, and a single strand oligonucleotide, was analyzed in depth by mass spectrometry and NMR spectroscopy. Interestingly, significant differences in the reactivity of the investigated compounds toward the various model biomolecules were observed: in particular we observed that <i>trans</i> complexes preferentially release their iodide ligands upon biomolecule binding, while the <i>cis</i> isomers may release the amine ligands with retention of iodides. Such differences in reactivity may have important mechanistic implications and a relevant impact on the respective pharmacological profiles

Quantum features of a barely bound molecular dopant: Cs2( 3Σu) in bosonic helium droplets of variable size

We present in this work the study of small 4He N-Cs2(3Σu) aggregates (2 ≥ N ≥ 30) through combined variational, diffusion Monte Carlo (DMC), and path integral Monte Carlo (PIMC) calculations. The full surface is modeled as an addition of He-Cs2 interactions and He-He potentials. Given the negligible strength and large range of the He-Cs2 interaction as compared with the one for He-He, a propensity of the helium atoms to pack themselves together, leaving outside the molecular dopant is to be expected. DMC calculations determine the onset of helium gathering at N = 3. To analyze energetic and structural properties as a function of N, PIMC calculations with no bosonic exchange, i.e., Boltzmann statistics, at low temperatures are carried out. At T = 0.1 K, although acceptable one-particle He-Cs2 distributions are obtained, two-particle He-He distributions are not well described, indicating that the proper symmetry should be taken into account. PIMC distributions at T = 1 K already compare well with DMC ones and show minor exchange effects, although binding energies are still far from having converged in terms of the number of quantum beads. As N increases, the He-He PIMC pair correlation function shows a clear tendency to coincide with the experimental boson-liquid helium one at that temperature. It supports the picture of a helium droplet which carries the molecular impurity on its surface, as found earlier for other triplet dimers. © 2011 American Chemical Society.This work has been supported by by DGICYT, Spain, Grant Nos. FIS2007-62006 and FIS2010-18132.Peer Reviewe