La Danse macabre de Guyot Marchant en Istrie (Beram, Hrastovlje)

The article considers two Histrian 'danses macabres', that of Beram (Croatia, attributed to Vincent of Kastav, dated 1474) and that of Hrastovlje, probably created by his nephew and supposedly executed fifteen years later. Having identified some details presented by both cycles it is possible to compare them to the text of the first known danse macabre, appeared in the Carnage of Saints-Innocents in Paris in the 1420s, edited by Guyot Marchand. The comparison reveals a certain number of innovations and variations with respect to a same circulating model throughout Europe, even if many features of the edited text are also present in the two Histrian frescoes

1H‐NMR metabolomic profiling of the crayfish Astacus leptodactylus subjected to polyphenol‐enriched diets

1H-NMR analysis of the hepatopancreas, muscle and haemolymph of Astacus leptodactylus after feeding with polyphenol-enriched diet is reported. 1H-NMR spectra of lipophilic extracts showed the presence of cholesterol, fatty acid residues, phospholipids and triglycerides. 1H-NMR spectra of aqueous extracts identified 35 metabolites in the hepatopancreas, 31 in the muscle and 22 in the haemolymph. A total of 20 metabolites (amino acids and their derivatives) were present in the hepatopancreas, the muscle and the haemolymph. A total of 10 metabolites were present in both the hepatopancreas and the muscle (five amino acids, 2-hydroxybutyrate, choline, myo-inositol, glycogen and uracil). 2-Hydroxyisobutyrate and creatine were present in both the hepatopancreas and the haemolymph. Phosphorylethanolamine, phosphocholine and fumarate were present only in the hepatopancreas and isoleucine only in the muscle. Statistical analysis showed that the percentage of weight gain was statistically higher in polyphenol-enriched diet groups compared to the control and that polyphenols had a stimulating effect on the general metabolism. No stress-related metabolites were higher in crayfish fed with polyphenol-enriched diet. Conversely, phosphatidylcholine, cholesterol and DHA, linked to resistance to environmental stress and diseases, were higher compared to the control diet. This study indicates that 1H-NMR is a useful tool to study the metabolomics in relation to diet differences

366 Combined exploratory immunophenotyping and transcriptomic tumor analysis in patients treated with OSE2101 vaccine in HLA-A2+ advanced non-small cell lung cancer (NSCLC) from the ATALANTE-1 trial

BackgroundOSE2101 (Tedopi®) is an anticancer vaccine with HLA-A2+ restricted modified epitopes targeting five tumor-associated antigens (TAAs) frequently expressed in lung cancer (CEA, HER2, MAGE2, MAGE3, P53). Step-1 results of the phase III, randomized, open-label ATALANTE-1 study comparing Tedopi® vs standard treatment (SoC) showed a favorable benefit/risk of Tedopi® over SoC (HR 0.71 for overall survival OS) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on immune checkpoint blockers (ICB).1 We analyze available tumor biopsies at initial diagnosis from some patients treated with Tedopi® to determine the expression of the 5 TAAs and to identify other tumor factors associated with long-term survival.MethodsTumor biopsies were available for 8 HLA-A2+ (blood test) stage IV NSCLC patients included in the trial. Primary (<12 weeks) and secondary (≥ 12 weeks) resistance to ICB were observed in 3 (38%) and 5 (62%) of patients. Best response to Tedopi® and OS were: 1 partial response (PR) (OS of 33 months), 3 stable disease (SD) (OS of 22, 26 and 41 mo.) and 4 disease progression (PD) (OS of 3, 4, 30 and 31 mo.). HLA-class I, PD-L1, CD8 T-cells, HER2, CEA and P53 tumor expression were evaluated by immunohistochemistry (IHC). NanoString gene expression profiling was performed using the Pan Cancer Immune gene set.ResultsHLA-class I was expressed in all tumor samples. IHC analysis revealed that P53, CEA and HER2 were expressed in 6/7, 5/7 and 0/7 patients, respectively. P53, CEA, HER2, MAGE2, and MAGE3 were detected at RNA level in 5/5 tested patients (table 1). IMMUNOSCORE® IC CD8/PDL1 analysis showed High/High, High/Low and Low/Low scores for 1/7, 1/7 and 5/7 patients, respectively. The High/High IMMUNOSCORE® with a pronounced CD8+ T-cell tumor infiltration was observed in the patient with PR. High percentage of tumor cells expressing P53 (69%–97%) and overexpression of genes associated with activated macrophages (TREM2, MARCO, SLC11A1, CHIT1, SERPINB2) were observed in the PR and SD patients. High IFN-gamma and Expanded Immune Gene Signature scores were observed in long-term survivor patients with secondary resistance to ICB, even after progressive disease.Abstract 366 Table 1Summary of clinical and translational dataCEACarcinoembryonic antigen; HER2: Human Epidermal Growth Factor Receptor-2; ICB: Immune checkpoint blocker; IHC: Immunohistochemistry; ND: Not determined; OS: Overall Survival; Patient ID: Patient identification; PDL1: Programmed death-ligand 1; PFS: Progression-free survival; ssGSEA: Single-sample Gene Set Enrichment Analysis. Blue bars = Length of overall survival; Green bars = Gene Signature upregulation; Red bars = Gene Signature downregulationConclusionsThis study shows that all HLA-A2+ patients (blood test), expressed HLA class I in the tumors at initial diagnosis. Transcriptomic data in the patients that benefited from Tedopi® showed activated macrophage pathway, high IFN-gamma and Expanded Immune Gene Signatures scores. These data will be validated on larger number of patients treated with Tedopi® after the step 2 analysis.AcknowledgementsWe thank Julie Le Boulicaut, François Montestruc and Constant Josse (eXYSTAT, Malakoff, France) for the statistical analysis, and HalioDx for the IHC and NanoString analysis.Trial RegistrationEudraCT number2015-003183-36; NCT number: NCT02654587ReferenceGiaccone, et al. Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (ICI): step 1 results of phase III ATALANTE-1 randomised trial. ESMO meeting 2020, abstract #1260MO.Ethics ApprovalThe study protocol and its related documents (including the patient information and informed consent form) received approval from the Institutional Review Board (IRB), and the Competent Authority prior to study initiation.ConsentEach patient gave his/her written informed consent prior to study enrolment

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distribution.Comment: 27 pages, 16 figure

Search for muon neutrinos from gamma-ray bursts with the ANTARES neutrino telescope using 2008 to 2011 data

9 pages, 8 figures; added Fig. 1 with effective area, updated Fig. 8 (b) according to arXiv:1204.4219 ; Références publication Astron Astrophys 559 (2013) A9International audienceAims. We search for muon neutrinos in coincidence with GRBs with the ANTARES neutrino detector using data from the end of 2007 to 2011. Methods. Expected neutrino fluxes were calculated for each burst individually. The most recent numerical calculations of the spectra using the NeuCosmA code were employed, which include Monte Carlo simulations of the full underlying photohadronic interaction processes. The discovery probability for a selection of 296 GRBs in the given period was optimised using an extended maximum-likelihood strategy. Results. No significant excess over background is found in the data, and 90% confidence level upper limits are placed on the total expected flux according to the model

Search for muon-neutrino emission from GeV and TeV gamma-ray flaring blazars using five years of data of the ANTARES telescope

The ANTARES telescope is well-suited for detecting astrophysical transient neutrino sources as it can observe a full hemisphere of the sky at all times with a high duty cycle. The background due to atmospheric particles can be drastically reduced, and the point-source sensitivity improved, by selecting a narrow time window around possible neutrino production periods. Blazars, being radio-loud active galactic nuclei with their jets pointing almost directly towards the observer, are particularly attractive potential neutrino point sources, since they are among the most likely sources of the very high-energy cosmic rays. Neutrinos and gamma rays may be produced in hadronic interactions with the surrounding medium. Moreover, blazars generally show high time variability in their light curves at different wavelengths and on various time scales. This paper presents a time-dependent analysis applied to a selection of flaring gamma-ray blazars observed by the FERMI/LAT experiment and by TeV Cherenkov telescopes using five years of ANTARES data taken from 2008 to 2012. The results are compatible with fluctuations of the background. Upper limits on the neutrino fluence have been produced and compared to the measured gamma-ray spectral energy distributionThe authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a l'energie atomique et aux energies alternatives (CEA), Commission Europeenne (FEDER fund and Marie Curie Program), Region Ile-de-France (DIM-ACAV) Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Stichting voor Fundamenteel Onderzoek der Materie (FOM), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; National Authority for Scientific Research (ANCS), Romania; Ministerio de Economia y Competitividad (MINECO), Prometeo and Grisolia programs of Generalitat Valenciana and MultiDark, Spain; Agence de l'Oriental and CNRST, Morocco. 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Search for a diffuse flux of high-energy νμ with the ANTARES neutrino telescope. Physics Letters B, 696(1-2), 16-22. doi:10.1016/j.physletb.2010.11.070Adrián-Martínez, S., Al Samarai, I., Albert, A., André, M., Anghinolfi, M., Anton, G., … Aubert, J.-J. (2012). SEARCH FOR COSMIC NEUTRINO POINT SOURCES WITH FOUR YEARS OF DATA FROM THE ANTARES TELESCOPE. The Astrophysical Journal, 760(1), 53. doi:10.1088/0004-637x/760/1/53Adrián-Martínez, S., Albert, A., André, M., Anghinolfi, M., Anton, G., Ardid, M., … Barrios, J. (2014). A search for time dependent neutrino emission from microquasars with the ANTARES telescope. Journal of High Energy Astrophysics, 3-4, 9-17. doi:10.1016/j.jheap.2014.06.002Adrián-Martínez, S., Albert, A., Al Samarai, I., André, M., Anghinolfi, M., Anton, G., … Aubert, J.-J. (2013). Search for muon neutrinos from gamma-ray bursts with the ANTARES neutrino telescope using 2008 to 2011 data. Astronomy & Astrophysics, 559, A9. doi:10.1051/0004-6361/201322169Abdo, A. 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Sperm whale long-range echolocation sounds revealed by ANTARES, a deep-sea neutrino telescope

[EN] Despite dedicated research has been carried out to adequately map the distribution of the sperm whale in the Mediterranean Sea, unlike other regions of the world, the species population status is still presently uncertain. The analysis of two years of continuous acoustic data provided by the ANTARES neutrino telescope revealed the year-round presence of sperm whales in the Ligurian Sea, probably associated with the availability of cephalopods in the region. The presence of the Ligurian Sea sperm whales was demonstrated through the real-time analysis of audio data streamed from a cabled-to- shore deep-sea observatory that allowed the hourly tracking of their long-range echolocation behaviour on the Internet. Interestingly, the same acoustic analysis indicated that the occurrence of surface shipping noise would apparently not condition the foraging behaviour of the sperm whale in the area, since shipping noise was almost always present when sperm whales were acoustically detected. The continuous presence of the sperm whale in the region confirms the ecological value of the Ligurian sea and the importance of ANTARES to help monitoring its ecosystemsThe authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a lenergie atomique et aux energies alternatives (CEA), la Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cite (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02), Region Ile-de-France (DIM-ACAV), Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Stichting voor Fundamenteel Onderzoek der Materie (FOM), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; National Authority for Scientific Research (ANCS), Romania; Ministerio de Economia y Competitividad (MINECO), Prometeo and Grisolia programs of Generalitat Valenciana and MultiDark, Spain; Agence de l'Oriental and CNRST, Morocco. 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Murchison Widefield Array limits on radio emission from Antares neutrino events

We present a search, using the Murchison Widefield Array (MWA), for electromagnetic (EM) counterparts to two candidate high-energy neutrino events detected by the ANTARES neutrino telescope in 2013 November and 2014 March. These events were selected by ANTARES because they are consistent, within 0°.4, with the locations of galaxies within 20 Mpc of Earth. Using MWA archival data at frequencies between 118 and 182 MHz, taken ~20 days prior to, at the same time as, and up to a year after the neutrino triggers, we look for transient or strongly variable radio sources that are consistent with the neutrino positions. No such counterparts are detected, and we set a 5s upper limit for low-frequency radio emission of ~1037 erg s-1 for progenitors at 20 Mpc. If the neutrino sources are instead not in nearby galaxies, but originate in binary neutron star coalescences, our limits place the progenitors at z 0.2. While it is possible, due to the high background from atmospheric neutrinos, that neither event is astrophysical, the MWA observations are nevertheless among the first to follow up neutrino candidates in the radio, and illustrate the promise of wide-field instruments like MWA for detecting EM counterparts to such events

El pensamiento político de la Contrarreforma y la razón de estado

This article reconstructs the history of political thought from the sixteenth to the first decades of seventeenth century: a period of strong conflicts between the religious sphere and the political changes of the states in their trajectory towards absolutism. The analysis of the polemic against Machiavelli, Bodin and the <em>politiques</em> shows how it was questioned at the conceptual and practical levels the autonomy of politics from religious morality and the tendency of the states to evade ecclesiastical control respectively. The schools of thought discussed here –from anti-Machiavellism to the encomiastic literature of the existent governments, from Tacitism to the reason State, to the critical writings of the society, mainly utopia- outline on the one hand, the effort to preserve an image of politics as just government, with a virtuous prince, but on the other, the inevitable commitment to the praxis of political realism, well represented by the developments of the concept of reason of State in Botero and other writers from the seventeenth century. It was only with the arrival of Modern natural law which brought to the fore the questions of the origin and purpose of civil society, that political thought partly detached from the eternal conflict between morals and political praxis opening the era of rational and scientific research and individual rights.<br><br>Este artículo reconstruye la historia del pensamiento político de la segunda mitad del siglo XVI a las primeras décadas del siglo XVII: un período de fuertes conflictos entre la esfera religiosa y los cambios políticos de los estados más avanzados hacia el absolutismo. El análisis de la polémica contra Maquiavelo, Bodin, y los <em>politiques</em> muestra como fueron cuestionados en el plano conceptual la autonomía de la política de la moral religiosa y en el plano práctico la tendencia de los estados a sustraerse del control eclesiástico. Las corrientes de pensamiento que se analizan aquí –del antimaquiavelismo a la literatura encomiástica de los gobiernos existentes, del tacitismo a la razón de Estado, hasta las escrituras críticas de la sociedad como la utopía- perfilan por un lado el esfuerzo de conservar una imagen de la política como gobierno justo, con un príncipe virtuoso, pero por el otro el inevitable compromiso con las praxis del realismo político, bien representado por la evolución del concepto de razón de Estado en Botero y en otros escritores del siglo XVII. Fue sólo con la llegada del derecho natural moderno, que puso en primer plano la cuestión del origen y los fines de la sociedad civil, que el pensamiento político se sustrajo en parte de la discusión sobre el eterno conflicto entre moral y praxis política para abrir la era de la investigación racional y científica y de los derechos individuales

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin