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Abstract: The determination of the energy spectrum features with low systematic uncertainty is crucial for interpreting the nature of cosmic rays. In this study, we conducted a measurement of the energy spectrum at the Pierre Auger Observatory using a surface detector with a calorimetric energy scale indirectly set by a fluorescence detector. The surface detector consists of an array of water-Cherenkov detectors that extends over 3000 km^2 with 1500m spacing. Additionally, two nested arrays of the same kind with 750m and 433m spacing were utilized to lower the energy threshold of the measurements. This contribution presents, for the first time, the spectrum measured with the 433m array, which reduces the energy threshold down to 63 PeV, nearly half the energy at which we previously published a steepening using the 750m array. Our measurements include a characterization of the spectral features of the flux steepening around 230 PeV, known as the second-knee. The study benefits from a nearly 100% duty cycle and geometrical exposure. Notably, this is the first simultaneous measurement of the second knee energy and spectral indexes before and after the break, using a surface detector with an energy scale predominantly independent of air shower simulations and assumptions regarding hadronic interaction models.
Keywords: ultra-high energy cosmic rays, Pierre Auger Observatory, hadronic interaction model, water-Cherenkov detectors
Published in RUNG: 23.01.2024; Views: 397; Downloads: 4
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Keywords: ultra-high energy cosmic rays, extensive air showers (EAS), EAS muonic component, hadronic interaction models, Pierre Auger Observatory
Published in RUNG: 29.04.2021; Views: 2222; Downloads: 0
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Abstract: TDP-43 (TAR DNA-binding protein) is an hnRNP that was identified as the main component of the brain inclusions characteristically found in patients suffering of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration. As an hnRNP protein, TDP-43 fulfills diverse roles in mRNA metabolism, localization and transport. Structurally, TDP-43 is composed of a well conserved N terminal domain (NTD), two RRM domains of which RRM1 is necessary for recognizing and binding to its target, UG rich RNA sequences, and the C-terminal domain (CTD) which is a Glycine rich domain. The CTD also contains a Q/N rich region that plays a key role in protein aggregation and interaction with another hnRNP proteins and polyglutamine repeats. This thesis focus on the structural determinants involved in the different TDP-43 interactions with itself and with other hnRNPs. Both the carboxyl and amino terminal domains are involved in these interactions. We have mapped the regions more relevant for the function of TDP-43 and for the aggregation process characteristic of the pathological pathway leading to neurodegeneration. We have started to further study the N-terminal domain. Previous results in our laboratory using a cellular aggregation model have shown that the N-terminal domain is also necessary for sequestering the endogenous TDP-43 into the aggregates. In particular, the intact NTD, specifically residues 1 to 77, have been shown to be needed to efficiently recruit TDP-43 monomers into these aggregates. We have extended our knowledge of NTD structure and function, by assessing the behavior of a series of proteins in which key structural features (α-helix and β-sheets) were modified and TDP-43 splicing function together with structure via NMR were analyzed. It was found that by disrupting protein secondary structure in the NTD (mutation in α-helix NTD-31V/R-32T/R) the capacity of the aggregates to sequester enough TDP-43 to induce loss of function was lost.In fact, this protein is also unable to recovery TDP-43 functionality when it is disrupted due to sequestration of the endogenous TDP-43 in add back experiments. Disturbing protein stability through substitution of residues in α-helix also affects its ability to form an active conformation. On the other hand, synthesis of hybrid peptides containing certain NTD and CTD segments was performed in order to see if they are capable to bind to the TDP-43 aggregates. However, it has been shown that these synthetic peptides have a greater ability to induce TDP-43 aggregation than to bind to them, probably due to specific functional characteristics of NTD and CTD segments used for their synthesis.The main focus of the thesis was on the C-terminal domain sequences involved in protein-protein interaction, misfolding and aggregation.A comparison of human, mouse, zebrafish, Annelida, flatworms and Drosophila showed a very strong conservation of the NTD and RRMs, but the C terminal regions of human and other TDP-43 orthologues are very different.I have studied Human and Drosophila melanogaster orthologues, because Drosophila orthologue contains different paralogs of TDP-43.Through a series of deletions and mutations it was shown that the shorter paralog of Drosophila TDP-43 (TBPH-RA) is more active than the longer one (TBPH-RC), and that this is due to a combination of two factors: 1. TBPH-RC by itself aggregates more than TBPH-RA, 2. The functionality of TBPH-RC is downregulated by intramolecular interactions in the C terminal domain. Apparently there is a cation-π interaction involving Tryptophan and Arginine in TBPH-RC that has a high relevance to the protein function and is lacking in the TBPH-RA.Overall this data has identified structural features essential for the proper function of TDP-43.In addition, we have also identified sequences that are critical in the pathological aggregation process of TDP-43 that lead to the characteristic brain inclusions in ALS and FTLD and to the loss of functionality
Keywords: TDP-43 structural determinants, hybrid peptides, protein-protein interactions, intramolecular interaction, cation-π interaction, Drosophila orthologues.
Published in RUNG: 22.07.2019; Views: 3356; Downloads: 190
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Keywords: Pierre Auger Observatory, shower universality reconstruction, hadronic interaction models
Published in RUNG: 16.02.2018; Views: 3379; Downloads: 150
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Abstract: With hybrid data of the Pierre Auger Observatory it is possible to measure the cross section of proton-air collisions at energies far beyond the reach of the LHC. Since the first measurement by the Pierre Auger Collaboration the event statistics has increased significantly. The proton-air cross section is now estimated in the two energy intervals in lg(E/eV) from 17.8 to 18 and from 18 to 18.5. These energies are chosen so that they maximise the available event statistics and at the same time lie in the region most compatible with a significant primary proton fraction. Of these data, only the 20% of most proton-like events are considered for the measurement. Furthermore, with a new generation of hadronic interaction models which have been tuned to LHC data, the model-dependent uncertainties of the measurement are re-visited.
Keywords: Pierre Auger Observatory, extensive air showers, proton-air cross section, hadronic interaction models
Published in RUNG: 03.03.2016; Views: 4557; Downloads: 196
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