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Durant tout le Paléolithique, les différentes productions lithiques réalisées présentent selon les cultures des caractéristiques morphométriques propres répondant aux fonctions précises auxquelles elles sont destinées. Elles procèdent donc nécessairement de choix techniques spécifiques de conception et de gestion des nucléus et du strict respect des modalités opératoires qu’impose le débitage. A cette règle répond naturellement le débitage laminaire qui, aux différentes périodes, bénéficie d’une normalisation optimale et adaptée des produits.Le nucléus de Port d’Envaux présenté ici, par ses propriétés morpho-techniques et dimensionnelles, intègre parfaitement les critères qui régissent la production de lames durant la seconde partie du Magdalénien. Cette découverte exceptionnelle confirme parfaitement l’originalité de ce concept de débitage qui, au cours de la première moitié du Tardiglaciaire, se développe entre le stade moyen-récent (MMR) et le stade supérieur (MS) de la culture. Throughout the Palaeolithic, the specific morphometric characteristics of stone tools varied according to the precise functions for which they were destined. Consequently, these elements reflect specific technical choices in terms of core conceptions and management as well as a strict respect for the rules governing the production sequence. This is particularly the case with blade production, which was geared around the manufacture of optimally standardised and adapted products.The morphological and technical properties as well as the size of the core found at the site of Port d’Envaux perfectly illustrates the criteria underlying blade production during the second part of the Magdalenian. This exceptional discovery succinctly demonstrates the distinctiveness of this production concept that emerged during the first half of the Late Glacial, between the Middle-Recent (MMR) and Upper (MS) Magdalenian.This large core preform was discovered by chance in the 1970s near the village of Saint-Vincent-de-Cosse (Dordogne) during work carried out in orchards on the structural bench of the lower terrace of the Dordogne River. Although this isolated object lacks a precise archaeological context, it was found in an area that was heavily frequented during the Upper Palaeolithic. Moreover, its position on a potential axis of circulation connecting more distant areas suggests the core was abandoned by Magdalenian groups.The core from Port d’Envaux must be seen in the context of several other pieces (about fifteen in total) discovered at the end of the 19th and beginning of the 20th century, whose particular shape and size and thus function intrigued researchers of the time. This new piece therefore provides an opportunity to rediscuss these particular artefacts commonly referred to as “large arched pieces” and, despite their unusual characteristics, confirm their being full-fledged blade cores.This contribution aims to provide a chrono-cultural context for this new large core from the Périgord region and highlight broader relationships between the southern and western parts of the Aquitaine Basin, where the technique has also been documented. A detailed technological analysis of the Port d’Envaux preform demonstrates this original technique to produce standardised blades sets it apart from other Upper Palaeolithic blade production systems, particularly those assigned to the Aurignacian and Gravettian.The preform was made on a large block of tabular flint and measures 40 cm in length. After shaping, the piece had a general bifacial outline, with the installation of two crests giving it a semi-ellipsoidal shape. These well-delineated crests serve to maintain the core’s relatively straight postero-lateral convexities, while those of the anterior surface ensure the removal of the first blade and guide the detachment of subsequent products. The convexity of the anterior surface of the core therefore predetermines the shape of the blades produced, guides reduction and gives it its characteristic section. The marked curvature of the crest, which both ensures the fluidity of reduction and the impressive length of the products, is therefore one of the most specific and original characteristics of this blade production system.In addition, the relative narrowness of the core (ca. 5.5 cm) is also very particular and implies that blades are removed primarily from the core’s surface and only minimally remove portions of either edge. Accordingly, blades are narrow and relatively thin, independent of their length, which is consistent with archaeological examples from the same production system. Our analysis shows a clear technological coherence of a number of industries documented in archaeological contexts or as isolated finds, thus confirming the attribution of large number of them to the same blade production concept. This being the case, a clear techno-cultural contemporaneity and technical parallels are also evident between different industries in the Aquitaine Basin dated to the same period.These technological similarities between preforms, on the one hand, and certain blade assemblages on the other hand, also repeatedly coincide with the selection of particular raw materials. While not exclusively the case, flint from Upper Campanian alterites in the Bergerac region, well suited for the production of big blades, was preferentially selected in many cases.A large number of pieces produced using this same method (including several large cores) are linked to this source of exceptional raw material. Moreover, these materials were transported over long distances between production sites in the Bergerac region and Magdalenian open-air or cave sites, notably in the Pyrenees. In light of this, we discuss issues concerning the general movement of artefacts and their transport over several hundred kilometres, particularly with regards to the cores. Several preforms, including the Pont d’Envaux example, bear technical details related to their eventual export. Given the novel aspect of this data, we provide a classic description accompanied by more interpretative elements.Certain details, notably the fact the both ends of the preform show no evidence of preparation, are particularly surprising. Despite its rather trivial and sometimes recurrent appearance, this distinctive feature is more than a simple technical convergence and may reflect a cultural norm. The striking fact that these large and heavy cores were transported over significant distances, perfectly preserved, almost ready to be reduced, lacking only the preparation of the striking platform, reveals a link between transported goods (the signifier) and symbols (the signified), a characteristic that most likely accompanied these objects both in practice and in terms of cultural traditions.

Micromagnets have wide applications in MEMS and micromotors but there are some limitations in current microfabrication processes for permanent magnets. A novel damage-free ultrashort pulsed laser machining process to manufacture complex shapes of Sm2Co17 micromagnets is proposed in this work. This process permits to cut the microparts submerged in a refrigerant fluid. This is especially beneficial for magnets, which are very sensitive to high temperature, as the heat effect of laser cutting on the hard magnetic materials is drastically reduced. The detailed description of the manufacturing process is here presented. Results of several machining processes like milling and cutting and the magnetic characterization of the resulting micromagnets are shown. Complex segment shapes, with 65 µm thickness are achieved, made in high quality Sm2Co17 material. It is demonstrated that no permanent degradation of the magnetic properties appears after laser machining.

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants. Ancient DNA data generation Before the LGM LGM in southwestern and western Europe Post-LGM in the Italian peninsula Post-LGM in western and central Europe Post-14 ka to Neolithic Phenotypically relevant variants Discussion and conclusions Methods

La obra cinematográfica del autor Orson Welles compone una reflexión profunda en torno a la idea de simulación. Desde su ópera prima, Ciudadano Kane, hasta su última película de ficción, Una historia inmortal, sus once largometrajes revelan la presencia reiterada de diversos objetos simbólicos que así lo evidencian: proyectores y cinematógrafos, máscaras y velos, reflejos y espejos, luces y sombras, o escenarios, que acompañan a la descripción diegética de simulaciones falaces o representaciones indeterminadas. Mediante el análisis formal de diferentes secuencias, pretendemos definir la postura que Welles ejerce en su cine frente a las ideas de verdad y falsedad, así como la naturaleza metadiscursiva de sus operaciones textuales.

Si l’on se réfère aux nombreuses traces de combustion en contexte archéologique, l’usage récurrent du feu au Paléolithique supérieur en Europe ne fait nul doute. Pourtant, et ce malgré les récentes avancées obtenues par la tracéologie lithique concernant les périodes antérieures ou postérieures, les procédés de production du feu employés au Paléolithique supérieur demeurent à ce jour quasiment inconnus. Après avoir exploré et évalué par l’expérimentation le succès de diverses modalités de contact pyrogène entre un sulfure de fer et diverses pièces lithiques et après avoir réalisé l’étude tracéologique de ces dernières, nous nous sommes concentrés sur la recherche systématique de telles traces sur l’industrie lithique de toute l’archéoséquence du Flageolet I (Bézenac, Dordogne, France). Les niveaux, d’un Aurignacien relativement ancien aux phases moyennes et récentes du Gravettien (d’après les dates radiocarbone : Rigaud et al. 1996), ont livré une quinzaine de pièces portant les caractères macroscopiques et microscopiques d’un contact tangentiel avec un sulfure de fer (e.g. pyrite ou marcasite), le plus souvent percussif. À l’échelle microscopique, les striations caractéristiques observées ont des orientations récurrentes, généralement parallèles à l’axe d’allongement des pièces, et cohérentes avec un usage en briquet, permettant d’écarter une origine taphonomique. L’ensemble des stigmates macro- et microscopiques, leurs localisations sur la pièce et relativement les uns aux autres, la morphologie et le gabarit des pièces nous permettent, par comparaison avec un référentiel expérimental sur mesure et au vu des données déjà disponibles dans la littérature, de proposer pour chaque zone utilisée un mode de fonctionnement. En ressort une grande diversité des supports employés comme briquets, de leur durée d’usage mais aussi des modalités de contact avec le sulfure de fer, que nous comparons aux quelques exemples recensés pour le Paléolithique supérieur et les périodes qui l’encadrent. If we refer to the many traces of combustion in an archaeological context, the recurrent use of fire in the Upper Paleolithic in Europe is beyond doubt. However, despite the recent advances obtained by lithic use-wear analysis concerning earlier or later periods, the means of producing fire during the Upper Paleolithic are almost unknown to this day. After having explored and evaluated through experimentation the success of various methods of contact between an iron sulphide and various lithic artifacts and after having carried out the use-wear analysis of the latter, we focused on the systematic search for such traces on the lithic material of all the archeosequence of Flageolet I (Bézenac, Dordogne, France). The levels, from a relatively early Aurignacian to the middle and recent phases of the Gravettian (according to the radiocarbon dates : Rigaud et al. 2016), have yielded some fifteen lithic artifacts with the macroscopic and microscopic attributes of tangential contact with iron sulphide (e.g. pyrite or marcasite), most often percussive. On a microscopic scale, the characteristic striations observed have recurrent orientations, generally parallel to the axis of elongation of the artefacts, and consistent with their use as strike-a-lights, making it possible to rule out a taphonomic origin. All the macro- and microscopic traces, their locations on the archeological pieces and relative to each other, the morphology and the size of the artifacts allow us, by comparison with a custom-made set of experimental lithics and in view of the data already available in the literature, to propose for each used zone an operating mode. This shows a great diversity of the supports used as strike-a-lights, of their duration of use and modes of contact with the iron sulphide, which we compare to the few examples identified for the Upper Paleolithic and the surrounding time periods.

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Cancer metabolic reprogramming promotes resistance to therapies. In this study, we addressed the role of the Warburg effect in the resistance to photodynamic therapy (PDT) in skin squamous cell carcinoma (sSCC). Furthermore, we assessed the effect of metformin treatment, an antidiabetic type II drug that modulates metabolism, as adjuvant to PDT. Methods: For that, we have used two human SCC cell lines: SCC13 and A431, called parental (P) and from these cell lines we have generated the corresponding PDT resistant cells (10GT). Results: Here, we show that 10GT cells induced metabolic reprogramming to an enhanced aerobic glycolysis and reduced activity of oxidative phosphorylation, which could influence the response to PDT. This result was also confirmed in P and 10GT SCC13 tumors developed in mice. The treatment with metformin caused a reduction in aerobic glycolysis and an increase in oxidative phosphorylation in 10GT sSCC cells. Finally, the combination of metformin with PDT improved the cytotoxic effects on P and 10GT cells. The combined treatment induced an increase in the protoporphyrin IX production, in the reactive oxygen species generation and in the AMPK expression and produced the inhibition of AKT/mTOR pathway. The greater efficacy of combined treatments was also seen in vivo, in xenografts of P and 10GT SCC13 cells. Conclusions: Altogether, our results reveal that PDT resistance implies, at least partially, a metabolic reprogramming towards aerobic glycolysis that is prevented by metformin treatment. Therefore, metformin may constitute an excellent adjuvant for PDT in sSCC, This research was supported by Spanish grants from Instituto de Salud Carlos III MINECO and Feder Funds (FIS PI15/00974; PI18/00858 and PI18/00708) and Ministerio de Ciencia, Innovación y Universidades (PID2019-108674RB-100)

La tecnología CCS (Carbon Capture and Storage) consiste en la captura, transporte (normalmente por tubería) e inyección y almacenamiento en reservorios geológicos (pozos de petróleo agotados, etc.) del CO2 producido en las actividades industriales. Es una de las opciones más importantes para reducir las emisiones de CO2 a la atmósfera y luchar contra el cambio climático: para 2050, está previsto almacenar más de 5 gigatoneladas por año a nivel global. El CO2 que se maneja no es CO2 puro, sino que contiene distintos tipos y cantidades de impurezas en función del proceso industrial del que procede y de los mecanismos de captura y purificación posterior. Las impurezas afectan de forma importante a las propiedades del fluido, propiedades que es necesario conocer para diseñar y operar las instalaciones CCS de forma idónea. Se utilizarán Ecuaciones de Estado (EoS) para calcular propiedades químico-físicas del CO2 puro y de un sistema CO2 + H2S + O2 con composición de interés para la tecnología CCS. Este cálculo se realizará en intervalos de presión y temperatura que incluyen los de las etapas de transporte, inyección y almacenamiento de la tecnología CCS (T = 263-373 K; p = 0,02-30 MPa).A partir de los valores obtenidos, se calcularán diferentes parámetros técnicos y se determinará cómo influye la presencia conjunta y por separado de O2 y H2S en las etapas de transporte, inyección y almacenamiento del proceso CCS: diseño del ceoducto (presión mínima de operación, caídas de presión y densidad y diámetro de tubería), proceso de inyección (flujo de permeación) y comportamiento del fluido en el reservorio de almacenamiento (capacidad de almacenamiento y velocidad ascensional de la pluma). No se han tenido en cuenta las diferencias de reactividad en el fluido por la presencia de las impurezas estudiadas.

Dar propina es un acto sencillo que no suele relacionarse con la entrega de grandes cantidades de dinero, pero dependiendo del lugar del mundo donde se dé, no solo eso cambia, sino también la norma social que hay detrás. Existe una serie de factores que alteran la percepción de los clientes a la hora de dar propina, y que completan los motivos por los que se suele dar. En este trabajo fin de grado se busca explicar esas causas y factores, además de tratar otros temas estrechamente relacionados con las propinas como son: la forma en que pagan impuestos, cómo son reguladas por la ley, los problemas de riesgo moral que conllevan o cómo se compaginan con los salarios.

El presente artículo analiza la representación de los cuerpos femeninos en los tres primeros largometrajes del director Carlos Vermut: Diamond Flash (2011), Magical Girl (2014) y Quién te cantará (2018). Mediante una perspectiva interdisciplinar que conjuga la semiótica y la teoría fílmica feminista, abordamos las modalidades de identificación articuladas por la enunciación respecto de los personajes femeninos protagonistas. Recurriendo al análisis textual como metodología, nuestro estudio concluye que las mujeres del universo vermutiano están condenadas a experimentar una corporeidad abyecta, forzadas a escoger entre la reinvención identitaria o la muerte.

PDAC has a low 5-year survival rate of ~10% which has not changed much over the past few decades. Desmoplasia, characterized by deposition of extracellular matrix (ECM) elements, such as collagen and hyaluronic acid (HA) is a hallmark feature of the PDAC (pancreatic ductal adenocarcinoma) microenvironment. The mechanical and biological barrier imposed by high desmoplastic content in PDAC tumors makes them refractory to conventional chemotherapeutics and is a major cause of immune cell exclusion, observed in these tumors, resulting in a dismal response to immunotherapy. Only ~1-3% of PDAC patients respond to immune checkpoint therapy, highlighting the need for novel therapeutic strategies to overcome treatment resistance observed in these tumors. In this regard, photodynamic therapy (PDT) and the associated phenomenon of photodynamic priming (PDP) has been demonstrated to overcome various physiological and mechanical barriers, in pre-clinical models of desmoplastic PDAC, and sensitizing them to subsequent therapies. PDT involves the administration of a relatively non-toxic molecule, referred to as photosensitizer, which can be activated by external irradiation and in the presence of molecular oxygen results in the formation of reactive molecular species (RMS). While the RMS generated during the process can induce immunogenic cell death it has been recently demonstrated to modulate ECM thereby permeabilizing the tumors to drugs and allowing for increased immune cell infiltration. In this study, using a syngeneic immunocompetent KPC PDAC model, we demonstrate that a single dose of Visudyne® (an FDA approved photosensitizer formulation) with irradiation at 100 J/cm2, significantly reduced tumor volume and increased survival (Median survival 36.5 days for the control group versus 43 days for the PDT-treated group). Mechanistically, apart from inducing cytotoxicity, PDT significantly reduced Hyaluronic acid content in these tumors leading to an enhanced immune cell infiltration. Importantly, regions of Hyaluronic acid depletion, 72 h post-PDT, were found to have a significantly higher CD4+ and CD8+ T-cell infiltration characterized by CD3+CD4+CD45+ and CD3+CD8a+CD45+ markers, respectively. Our ongoing work is aimed at studying the effect of combining immune checkpoint therapy with PDT for improving survival in these PDAC mouse models. Collectively, these results demonstrate the potential of PDT to not only induce immunogenic cell death in PDAC tumors, but also positively modulate tumor ECM components resulting in an enhanced immune cell infiltration. While the role of ECM in PDAC is extremely complex with both tumor restraining and tumor promoting roles, the potential of a single clinically approved treatment modality, PDT, in modulating ECM and enhancing immunogenicity warrants further investigation in a tumor type which has not benefitted much from conventional therapies. Citation Format: Mohammad A Saad, Jimena Nicolás Morala, Zhiming Mai, Tayyaba Hasan. Photodynamic therapy modulates extracellular matrix and induces anti-tumor immune responses in an orthotopic pancreatic cancer model [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B51.

Si l'on se réfère aux nombreuses traces de combustion en contexte archéologique, l'usage récurrent du feu au Paléolithique supérieur en Europe ne fait nul doute. Pourtant et ce malgré les récentes avancées obtenues par la tracéologie lithique concernant les périodes antérieures ou postérieures, les procédés de production du feu employés au Paléolithique supérieur demeurent à ce jour quasiment inconnus. Après avoir exploré et évalué par l'expérimentation le succès de diverses modalités de contact pyrogène entre un sulfure de fer et diverses pièces lithiques et après avoir réalisé l'étude tracéologique de ces dernières, nous nous sommes concentrés sur la recherche systématique de telles traces sur le registre lithique de toute l'archéoséquence du Flageolet I (Bézenac, Dordogne, France). Les niveaux de l'Aurignacien ancien aux phases moyennes du Gravettien ont livré une quinzaine de pièces portant les caractères macroscopiques et microscopiques d'un contact tangentiel avec un sulfure de fer (e.g. pyrite ou marcasite), le plus souvent percussif. A échelle microscopique, les striations caractéristiques observées ont des orientations récurrentes, généralement parallèles à l'axe d'allongement des pièces, et cohérentes avec un usage en briquet, permettant d'écarter une origine taphonomique. L'ensemble des stigmates macroet microscopiques, leurs localisations absolue et relative, la morphologie et le gabarit des pièces nous permettent, par comparaison avec un référentiel expérimental sur mesure et au vu des données déjà disponibles dans la littérature, de proposer pour chaque zone utilisée un mode de fonctionnement. En ressort une grande diversité des supports employés comme briquets, de leur durée d'usage mais aussi des modalités de contact avec le sulfure de fer, que nous comparons aux quelques exemples recensés pour le Paléolithique supérieur et les périodes qui l'encadrent.

Rare-earth transition metals thin films have attracted a lot of attention due to their high magnetic anisotropy that makes them great candidates for several applications including high density magnetic recording, microelectromechanical systems and actuators. Rare-earth based thin films also allow the development of novel spintronic devices and they are essential materials for energy-related technologies. Furthermore, the study of certain elements in these rare-earth based systems such as interfaces, grain boundaries or interstitial additions can provide a wider knowledge of their coercivity and magnetization reversal mechanisms. The aim of this study is to analyze the first stages of the growth of NdFeB thin and ultra thin films. For that purpose, NdFeB thin films have been grown on a MgO (001) substrate at 600ºC. An underlayer of 10 nm of Fe was previously grown in order to ensure epitaxiality. A 15 nm vanadium capping layer was deposited afterwards to prevent oxidation., {"references":["A. Morisako et al., J. Magn. Magn. Matter. 304, 46-50 (2003)","X. Liu et al., J. Appl. Phys. 97, 10K301 (2005)","T.-S. Chin, J. Magn. Magn. Matter. 209, 75-79 (2000)","A. Bollero et al., Nanoscale, 12, 1155-1163 (2020)","O. Gutfleisch et al., Adv. Mater. 23, 821–842 (2011)","L. Zha et al., J. Magn. Magn. Matter. 514, 167128 (2020)","S. Bance et al., Appl. Phys. Lett. 104, 182408 (2014)"]}