Drugs targeting a single TK/RTK in the treatment of solid cancers has not had the same success seen in blood cancers. This is, in part, due to acquired resistance in solid cancers arising from a range of mechanisms including the upregulation of compensatory RTK signalling. Rather than attempting to inhibit individual compensatory RTK—requiring knowledge of which RTKs are upregulated in any given tumour—strategies to universally inhibit signalling from multiple RTKs may represent an effective alternative. Endosomal trafficking of RTKs is a (...) common conduit that can regulate signalling from multiple RTKs simultaneously. As such, we posit that targeting endosomal trafficking—in particular, aberrant post‐translational modifications in cancers that contribute to dysregulated endosomal trafficking—could inhibit oncogenic signalling driven by multiple RTKs and pave the way for the development of a novel class of inhibitors that shift the trafficking of RTKs to inhibit tumour growth. (shrink)

Ana‐Carolina Gutiérrez‐Xivillé präsentiert eine neue Lesart zu Kants Grundlegung zur Metaphysik der Sitten. Während ältere Studien die kantische Ethik als bloße Ausarbeitung von bereits in den 1760er Jahren vorliegenden Begriffen lesen, zeigt diese Studie eine Neubestimmung des Freiheitsbegriffs und bietet eine gewandelte Sicht auf das Verhältnis zwischen „Moralvermögen“, „moralischem Gefühl“ und „Moralprinzip“. Gutiérrez‐Xivillé betrachtet die Texte weder isoliert noch monolithisch. Ihre aus einem analytischen und einem exegetischen Moment bestehende Methode erfasst Kants bekannte Schriften ebenso wie in jüngerer Zeit neu edierte, (...) wenig erforschte Materialien. Dabei offenbaren sich strukturelle Brüche, die wegweisend von einer frühen Moralkonzeption in eine spätere überleiten. Die Ethik Kants erweist sich als Ergebnis eines allmählichen Heranreifens über mehrere Stationen hinweg. (shrink)

From an early age, exposure to a spoken language has allowed us to implicitly capture the structure underlying the succession of speech sounds in that language and to segment it into meaningful units. Statistical learning, the ability to pick up patterns in the sensory environment without intention or reinforcement, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language, including the discovery of word boundaries in the continuous acoustic stream. Although extensive evidence has (...) been gathered from artificial languages experiments showing that children and adults are able to track the regularities embedded in the auditory input, as the probability of one syllable to follow another syllable in the speech stream, the developmental trajectory of this ability remains controversial. In this work, we have collected Event-Related Potentials while 5-year-old children and young adults were exposed to a speech stream made of the repetition of eight three-syllable nonsense words presenting different levels of predictability to mimic closely what occurs in natural languages and to get new insights into the changes that the mechanisms underlying auditory statistical learning might undergo through the development. The participants performed the aSL task first under implicit and, subsequently, under explicit conditions to further analyze if children take advantage of previous knowledge of the to-be-learned regularities to enhance SL, as observed with the adult participants. These findings would also contribute to extend our knowledge of the mechanisms available to assist SL at each developmental stage. Although behavioral signs of learning, even under explicit conditions, were only observed for the adult participants, ERP data showed evidence of online segmentation in the brain in both groups, as indexed by modulations in the N100 and N400 components. A detailed analysis of the neural data suggests, however, that adults and children rely on different mechanisms to assist the extraction of word-like units from the continuous speech stream, hence supporting the view that SL with auditory linguistic materials changes through development. (shrink)

Estudos recentes vêm revisando a composição da literatura que, ao longo do século XVIII serviu como base às ciências em território britânico. Segundo esses estudos, os seiscentistas de fala inglesa dedicaram-se a duas linhagens de texto, originadas em concepções de ciência muito distintas. Uma dessas linhagens tinha como fonte principal a antiga “literatura do segredo” que incluía desde velhos e sigilosos manuais de ofício até os milenares e proibidos tratados de hermética, literatura antes reservada a poucos. Diferente dessa, a outra (...) ]inhagem de textos surgia como um direto da proposta baconiana para a nova ciência: um saber elaborado por muitos e ao alcance de todos. Exemplos conhecidos dessa linhagem são os livros de divulgação utilizados pelos comenianos ingleses ou mesmo os relatórios, atas e memórias das sociedades científicas, geradores dos primeiros embriões de periódicos dedicados às ciências. Todavia, sob essa aparente contraposição das duas linhagens, há indícios de um profícuo diálogo - expresso sobretudo na correspondência e diários pensadores da época. (shrink)

Este trabajo es el ganador de la III Olimpiada de Filosofía que organiza FICUM en la modalidad de secundaria. Ana Timonet presentó su particular respuesta a la pregunta por el camino de la felicidad.

Firstly, this paper aims to analyze how verbal and visual modes contribute to build two basic components of cartoons: the referenced situation and the fictional situation. Secondly, it aims to unravel the semiotics of this discursive genre by offering a fine-grained picture of modal variations and continuities of the rhetorical resources deployed, by means of which the fictional situation is displayed. The corpus is composed of 50 multimodal cartoons chosen by cartoonists of 22 nationalities as the most representative of their (...) work in the frame of a wide questionnaire. Category analysis and non-parametric statistics were applied. We identified and fleshed out four different types of modal functioning of resources: visual preference, verbal preference, modal flexibility, and genuine multimodal functioning. Even if visual and multimodal metaphor were often in charge of transferring meaning from fiction to the referenced situation, results show that other resources such as antithesis, irony, and syllepsis can become the key resources of cartoons. Findings highlight the multilayered functioning of cartoons, among which plastic features can play a significant role, and provide further evidence in favor of the hyperdetermination of humor hypothesis proposed by Attardo. (shrink)

The Fourth Industrial Revolution based on digitalization, the development of AI, robotics, big data, and increasing automation is dredging up older debates on the end of human work. This article contributes to this debate arguing that these changing circumstances represent an opportunity to advance a renewed consideration of human work. By emphasizing its most distinctively human dimensions, including gratuitousness, relationality, and meaningfulness, we propose the articulation of a social model that recognizes relational goods as a specific contribution of human work (...) in an attempt to overcome the state and the market's monopoly of public life built around the dichotomy between the private and the public. Such a social model is based on the concept of circular subsidiarity, which represents a departure from traditional notions of subsidiarity by promoting a dynamic and reciprocal interplay between three essential societal spheres: the state, the market, and organized civil society, all of which have their role to fulfill by providing security, efficiency, and relational goods. Ultimately, this article suggests that circular subsidiarity can lead to a more inclusive and equitable social model by acknowledging how relational goods not only humanize civil society but also sustain the functioning of both the market and the state. (shrink)

El discurso primordialista sobre el origen de las identidades sociales etno-nacionales sigue latiendo en algunos enfoques históricos, antropológicos, políticos y jurídicos de las sociedades modernas, camuflado en otras formas iusnaturalistas y biologicistas de concebir los atributos culturales, étnicos, religiosos, conductuales, e incluso económicos de los pueblos. Este artículo pretende presentar, por el contrario, la construcción de las identidades nacionales desde el punto de vista modernista y analizar su papel como discurso que pretende reforzar estructuras de poder, producidas porque tienen utilidad (...) estratégica para el logro de bienes materiales o políticos, formalmente en nombre del grupo, pero de hecho solamente con objeto de dar ventaja a los líderes o las élites. Cuando llevan aparejado un carácter político, las identidades nacionales, culturales y étnicas son susceptibles de provocar conflictos violentos, la naturalización de la violencia y la deshumanización de otros grupos tienen lugar a menudo cuando de conflictos etno-nacionalistas se trata. (shrink)

This research study aims to determine the ontological arguments related to the existance of God. Some recent studies also proposed the argument that God is not a person, and this argument in pantheism and Swinburnian is mismatched with the statement that God is a person. Some people believe in pantheism and think that God is a part of the world, but in Swinburnian, people think that God is not a part of the world as these two thoughts conclude that God (...) is not a person. Based on these two ideas, the religious philosophers have choices, and they do not evidence that pantheism and Swinburnian reject the argument that God is a person. This philosopher also thinks that they cannot believe anymore in God. Some philosophers also believed this idea was new and not accepted by most religions. Overall research concluded that the existence of God and ontological arguments related to it are complex research and have glinted debate for centuries. Earlier, Anselm's argument against current debates on God's existence faced abundant criticism. In philosophy, the existence of God remains a challenging question. These topics endure lies to discuss about God's existence, and this conversation continues for argument and criticism by different philosophers and religious leaders. (shrink)

Edition of the commentary on Aristotle's De interpretatione by an anonymous Parisian master from the first half of the 13th century.

In this paper we will suggest that a hypertextual representation of the text allows us to show different temporal layers of reading and lets us add new ones. We use the notion “layers of reading” as a metaphor to explain how, historically, each reading of a text creates a new layer, an independent “stratum of meaning” -to use a geological term-, that is superimposed to a previous reading. We think the digital edition and the digital reading could create a philosophical (...) methodology, based on the awareness of the historical construction of each layer of reading. (shrink)

In the Nicomachean Ethics, Aristotle has given a tableau of the desirable virtues and their infringement through the surpassing of their limits. Thus, every virtue is framed or delimited by vices that represent either its excess or its deficiency. However, this type of defining is related to deep, metaphysical reasons: since every being, especially the living one, has its telos. Man’s telos is to practise and fulfil his human specificity, i.e. reason, and reason is the measure/quality of virtue as such; (...) the excess or deficiency in his behaviour perverts and even stops the realisation of the humanity of man. And this humanity is, in turn, in accordance to the telos of nature, the good in and for the preservation of all things. If, hypothetically, persons would not be virtuous at all, this accordance would not be realised and man would be an accident in the logic of nature: and accidents are removed, sooner or later. The criterion of the “quantitative” moral evaluation is thus qualitative: a quality, the good aimed at by mindfulness applied to the concrete particular moral relations and learned from experience. (shrink)

This review essay explores recent historical and anthropological literature on the emergence and development of transcultural psychiatry in the second half of the twentieth century. It examines how postcolonial psychiatry attempted to remove itself from its erstwhile colonial frameworks and strove to introduce new concepts and paradigms to make itself relevant in the context of decolonization and postwar reconstruction. The essay looks at both continuities and discontinuities between colonial and post-colonial transcultural psychiatry, asking how the recent surge of scholarly literature (...) in this field engaged with these issues. It also aims to identify the most important avenues for future research. (shrink)

Este artículo estudia críticamente el concepto de Ius Constitutionale Commune Latinoamericanum como fenómeno de judicialización de la política a nivel regional. Partiendo de la afirmación de que el derecho constitucional es político, se analizan algunos rasgos del ICCAL como la ideología que lo inspira, la teoría en que se apoya el concepto y el arreglo institucional que lo sostiene, para problematizar su carácter "común". Bajo el entendido que cualquier proyecto constitucional está indisolublemente ligado a un diseño institucional que lo lleva (...) a cabo, se critica la apuesta por un modelo juricentrista, anclado en la interpretación que la Corte Interamericana de Derechos Humanos hace de los derechos reconocidos como universales, para proponer un sistema basado en procedimientos deliberativos e igualitarios que fortalezcan la democratización de la región. This article critically examines the concept of Ius Constitutionale Commune Latinoamericanum as a phenomenon of judicialization of politics at the regional level. To problematize its "common" character and based on the assertion that constitutional law is political, some features of the ICCAL are analyzed: the ideology that inspires it, the theory in which the concept is supported and the institutional arrangement that sustains it. Under the understanding that every constitutional project is inextricably linked to an institutional design that carries it out, the commitment to a jury-centered model, anchored in the interpretation that the Inter-American Court of Human Rights makes of the rights recognized as universal is criticized. Proposing, in contrast, a system based on deliberative and egalitarian procedures that strengthen the democratization of the region. (shrink)

Psychological interest in Meritocracy as an important social norm regulating most of the western democratic societies has significantly increased over the years. However, the way Meritocracy has been conceptualized and operationalized in experimental studies has advanced in significant ways. As a result, a variety of paradigms arose to understand the social consequences of Meritocracy for intergroup relations; in particular, to understand the adverse consequences of Meritocracy for disadvantaged group members. The present research seeks to understand whether there is strong support (...) for the idea that (manipulated) Meritocracy disproportionally affects members of low status groups, and also to understand which specific components of this norm have been successfully manipulated and to what consequences. And this is particularly important given the recent call for greater transparency in how the success of experimental manipulations is reported. Thus, we carried out a systematic review examining the content of different prime tasks, summarizing prime manipulation checks’ effectiveness, and analyzing whether priming Meritocracy leads to less favorable orientations toward low status groups. Results across 33 studies revealed that despite the existing differences in the components highlighted, the salience of any of the Meritocracy dimensions facilitates the use of internal causal attributions, negative evaluations and stereotyping towards low status groups, affecting negatively decisions involving low-status group members, particularly in specific domains, as organizational contexts. These results carry both practical and theoretical implications for future research on the role of Meritocracy in intergroup settings. (shrink)

Pocos fenómenos han suscitado tanto debate en América Latina como es la cuestión de su integración, que, a pesar de sus luces y sus sombras, sus avances y retrocesos, sigue ahí, presente, a pesar de las incertidumbres que los diferentes acontecimientos políticos generan sobre su futuro próximo.

The traditional perspective on emotions assumes an unassailable dualism between emotions and reason. For common sense, including legal common sense, emotions are always dangerous and have nothing to do with rational decision-making. Nonetheless, the Aristotelian perspective regarding the relationship between emotions and reason is extremely enlightening. The relationship between emotions and law has been studied by a large range of scholars from different legal movements and with diverse objectives. This chapter is based on three theoretical pillars: Aristotle’s theory of emotions (...) as elaborated in Rhetoric and Nicomachean Ethics, Aristotle’s view on the close relationship between reason, emotions and phronesis as elaborated in the Nicomachean Ethics, and a specific contemporary view: Jurisprudentialism. We assert that through a Jurisprudentialist analysis of Law as an open task and through Aristotle’s account of emotions, the challenges of legal education could be more realistically reassessed. (shrink)

Pretendemos analisar a crítica ao direito marxiana exposta nos comentários à obra Lectures on the early history of institutions, do jurista inglês Henry Sumner Maine, presentes nos "assim chamados" Cadernos Etnológicos. Para tal, passaremos pela crítica de Karl Marx à teoria do direito de Maine, passando também por considerações sobre os juristas analíticos John Austin e Jeremy Bentham, nos quais o autor das Lectures se baseia fortemente. Em seguida, trataremos das críticas à concepção de Maine sobre a origem do Estado (...) e do direito. Então, explicaremos como Marx se contrapõe a Maine voltando-se para o solo da história real, e assim analisa a gênese e o desenvolvimento direito na Irlanda e sua associação com a religião cristã, tanto antes quanto durante a colonização inglesa, observando também a violência por trás da imposição das leis coloniais. (shrink)

As grandes epidemias de peste que atingiram ao longo de muitos séculos os ingleses, refletiram mudanças importantes para os conhecimentos de cada período histórico. Esse artigo busca unir duas extremidades de um decorrer de grandes catástrofes epidemiológicas na Inglaterra, com um olhar especial à populosa Londres, começando com a primeira entrada da peste bubônica na cidade, em 1348, e seu provável último grande surto, em 1665. Os dois episódios tocados aqui são apresentados sob a perspectiva das novidades, semelhanças e diferenças (...) entre essas duas pontas da história, passando pelas novas respostas da medicina no século XIV e os princípios de uma ‘aritmética política’ no século XVII. Para esse fim, são de extrema importância diferentes fontes, como as inúmeras cópias do tratado médico de John de Burdeaux, escritos a partir de 1390, e o Observations de John Graunt, publicado a partir de 1662. (shrink)

El presente trabajo trata de abordar la forma testimonial de Ernst Jünger de dar cuenta de la historia con el propósito, en primer lugar, de indagar en el sentido que tiene para el autor alemán la experiencia de la catástrofe, la guerra y el dolor y, en segundo lugar, de explicar los elementos constitutivos de su particular concepto de historia.

Recently, approach-avoidance tendencies and visual perception biases have been increasingly studied using bistable point-light walkers (PLWs). Prior studies have found a facing-the-viewer bias when one is primed with general threat stimuli (e.g. angry faces), explained by the “error management theory”, as failing to detect a threat as approaching is riskier than the opposite. Importantly, no study has explored how disease threat – linked to the behavioural immune system – might affect this bias. This study aimed to explore whether disease-signalling cues (...) can alter how we perceive the motion direction of ambiguous PLWs. Throughout 3 experiments, participants indicated the motion direction of a bistable PLW previously primed with a control or disease-signalling stimuli – that is, face with a surgical mask (Experiment 1), sickness sound (Experiment 2), or face with a disease cue (Experiment 3). Results showed that sickness cues do not significantly modulate the perception of approach-avoidance behaviours. However, a pattern emerged in Experiments 2 and 3, suggesting that sickness stimuli led to more facing away percepts. Unlike other types of threat, this implies that disease-related threat stimuli might trigger a distinct perceptual bias, indicating a preference to avoid a possible infection source. Nonetheless, this finding warrants future investigations. (shrink)

Publicada en 1979, Violence se desarrolla en la ciudad nigeriana de Benín, durante el boom petrolífero de la década de 1970. La narrativa se centra en dos matrimonios que representan ambos extremos del espectro social, cuyos caminos se cruzan mientras sortean diversos obstáculos. La novela de Iyayi constituye una crítica marxista de la violencia ejercida por la pobreza y la desigualdad extrema. Violence muestra cómo ciertos cuerpos humanos se cosifican y explotan de manera sistemática, a la vez que aquellos que (...) no generan ganancias son descartados sin el menor rastro de humanidad. Desde la perspectiva de la ecocrítica urbana, este artículo examina instancias de cosificación corporal en la novela y, específicamente, de comoditización de energía y materia humanas entendidas como recursos naturales. El estudio propone que Iyayi no solo critica esta comoditización al presentarla como una consecuencia del proyecto capitalista, sino que también la cuestiona mediante actos de cuidado resistente que devuelven a los cuerpos cosificados su calidad de sujeto. Estos actos de cuidado constituyen una forma de refutar la separación artificial de Naturaleza y Sociedad, contenida en el dualismo de cuerpo y mente, que históricamente ha justificado la explotación y expropiación capitalista (neo)colonial. El presente artículo contribuye entonces tanto al campo de los estudios poscoloniales como a los de ecocrítica urbana y literaturas africanas, centrándose en una obra relativamente poco analizada y en problemáticas sumamente relevantes para la Nigeria contemporánea. (shrink)

É largamente reconhecido no interior dos estudos das Humanidades, em especial no campo da Filosofia, a lacuna deixada acerca da compreensão do papel das mulheres e da sua produção intelectual no pensamento filosófico. Tal preocupação deve-se, em grande parte, à produção divulgada por outras áreas de estudos, como as de gênero e da teoria feminista. No caso do campo filosófico, trata-se de reconhecer que a história da filosofia nunca foi feita só por homens, ainda mais quando se tratou da defesa (...) da liberdade das mulheres e da sua luta por inserção e reconhecimento intelectuais. Neste sentido, este trabalho visa analisar comparativamente três discursos em defesa da liberdade das mulheres, escritos por duas jovens autoras e um autor, em momentos distintos. Em primeiro lugar, temos o discurso de um jovem professor de retórica, Lorenzo Valla, contido no seu diálogo Do Prazer, de 1431; em segundo, temos o diálogo Il Merito delle Donne, da escritora veneziana Moderata Fonte, publicado postumamente em 1600; e, por fim, o texto da Tirannia Paterna, de outra escritora veneziana, a filósofa Arcangela Tarabotti, publicado postumamente em 1654. Em todos os três casos, tratam-se de discursos endereçados aos homens, em repúdio por seus crimes cometidos contra a liberdade das mulheres e o livre-arbítrio em geral. Desse modo, tomando como eixo de análise a semelhança temática entre tais textos, será de nosso interesse observar a relação entre o ethos dos falantes com o self dos autores nessas três orações distintas, levando em consideração ainda o gênero de discurso, a audiência, os efeitos retóricos e o contexto em que as obras se inscreveram. (shrink)

El presente artículo determina cómo una empresa ética, convertida en escuela de virtudes morales, puede contribuir a mejorar la sociedad. La empresa sólo puede mejorar la sociedad y generar un impacto positivo en la misma desde la ejemplaridad de todas y cada una de sus personas. Se entiende la empresa como una comunidad de personas en la que ha de existir un equilibrio esencial entre lo individual y lo colectivo. Se parte de la premisa de que la empresa es, también, (...) un espacio ético que puede llegar a convertirse en una escuela de valores y virtudes en la que los profesionales desarrollen sus capacidades humanas en interrelación con los demás. Se argumenta la relevancia de la virtud empresarial, desde la perspectiva de la transformación del ethos individual, de los hábitos de las personas que forman la organización. Se considera que la empresa puede llegar a convertirse en una “escuela de valores y virtudes”. La forja del ethos ético y virtuoso de los profesionales es, a su vez, la esencia de la construcción del ethos ético de la empresa que tendrá su correspondiente impacto en el ethos de una buena sociedad. A partir de estas aseveraciones nos hacemos las siguientes preguntas en nuestra investigación: ¿De qué manera puede influir el ethos de la empresa en la configuración de los ethos particulares de los profesionales que forman parte de ella? y ¿cómo puede la empresa contribuir al desarrollo de las virtudes morales de sus personas? Asumiendo estas dos cuestiones como base de la investigación, se argumenta que la empresa puede llegar a ser, a través del trabajo, una ‘escuela’ para el desarrollo de las virtudes morales y, desde ahí, contribuir a la construcción de una sociedad más humana. (shrink)

O artigo faz uma reflexão crítica dos impactos da pandemia para as crianças da Educação Infantil no Brasil. Delineia algumas concepções de criança e infância nos discursos normativos, apontando possibilidades que valorizem a experiência infantil.

I mention the main, technophile and technophobe, positions towards technology in the Western 18th century, as the criterion of this paper. Then I show that, however unexpected would this be, the concept of technics – opening the problem of technics – was explicitly present within the transcendental philosophy. From its multiple meanings outlined in the logic of this philosophy, I focus on the technical instruments of science. Kant considered them optimistically, but insisted that they are only means subordinated to the (...) capability of reason that alone is able to give knowledge. And the vault key of knowledge is the moral law (the moral telos) given by the human reason. Thus, answering to Rousseau, Kant indicates that the progress of knowledge is ultimately determined by this moral, and not by the enrichment of cognisance as a result of technical instruments. If we consider them as a model for the treatment of the technical objects in the broad sense of this term, Kant introduced the criticism of the technophile reductionism, while creating the frame of the positivist science and the humanistic philosophy of the 19th century. Keywords: Kant, technical instruments of science, technic/technology, technophilia and technophobia, moral law. (shrink)

Existe una escisión del hombre con la naturaleza inscrita en los aspectos de la vida; la civilización moderna está en crisis ambiental, de la cultura, de sentido, de la técnica y de la manera en que habita y crea hábitat el hombre. La técnica moderna se ha instaurado de la mano de la ciencia y la economía llamándose tecnología: una manera de la techné distanciada de sus orígenes y que ha pasado de la creación e invención a una repetibilidad que (...) solo permite crear lo que cumple las condiciones e ideales establecidos por un modelo económico. Mientras la techné se comprende en un mundo de la vida, en un lugar con espacio y tiempo, la técnica moderna se cree separada de él. Se propone entonces un giro en el pensar/habitar hacia la techné, para un reencuentro con el mundo de la vida. (shrink)

This article examines the NEET (Not in Education, Employment, or Training) youth in Romania, employing the secondary analysis of quantitative data and focusing on the socio-economic, cultural and systemic factors contributing to this phenomenon. The analysis highlights how economic instability, poverty and limited access to education exacerbate the challenges faced by this demographic group. Gender disparities, driven by traditional roles and labour market discrimination, further limit opportunities for young women. Additionally, structural deficiencies in the labour market, such as job shortages (...) and mismatches between skills and demand, hinder employment prospects. Cultural expectations and societal norms also play a significant role in influencing youth participation in education and employment. Young citizens of Romania, particularly women and members of the Roma community, face significant barriers to employment, with low wages, poor working conditions and inadequate investment in education and vocational training contributing to high NEET youth rates. Patriarchal norms, especially within the Roma community, further exacerbate cycles of poverty and marginalisation by limiting educational and economic opportunities. (shrink)