Second harmonic generating (SHG) nanoprobes have recently emerged as versatile and durable labels suitable for in vivo imaging, circumventing many of the inherent drawbacks encountered with classical fluorescent probes. Since their nanocrystalline structure lacks a central point of symmetry, they are capable of generating second harmonic signal under intense illumination – converting two photons into one photon of half the incident wavelength – and can be detected by conventional two‐photon microscopy. Because the optical signal of SHG nanoprobes is based on (...) scattering, rather than absorption as in the case of fluorescent probes, they neither bleach nor blink, and the signal does not saturate with increasing illumination intensity. When SHG nanoprobes are used to image live tissue, the SHG signal can be detected with little background signal, and they are physiologically inert, showing excellent long‐term photostability. Because of their photophysical properties, SHG nanoprobes provide unique advantages for molecular imaging of living cells and tissues with unmatched sensitivity and temporal resolution. (shrink)

Die vorliegende Studie erschließt erstmals umfassendden Zurechnungsbegriff in Kants praktischer Philosophie. Ein Zurechnungsurteil bringt zum Ausdruck, dass eine Handlung auf den freien Willen einer bestimmten Person zurückgeführt wird. Zurechnung ist ein zentraler Begriff des Rechts und von grundlegender Bedeutung für unsere alltägliche Praxis, wenn wir andere Personen loben, tadeln oder dankbar sind. Eine fundamentale Relevanz des Zurechnungsbegriffs zeigt die Autorin auch für Kants praktische Philosophie auf. Ausgehend von Kants Definition des Zurechnungsbegriffs in der Metaphysik der Sitten wird deutlich, wie Zurechnung (...) mit anderen zentralen Begriffen von Kants Handlungs- und Moraltheorie verknüpft ist: sowohl für die Auflösung der Freiheitsantinomie als auch für den Begriff der Person als freiem, moralischem Subjekt und Träger eines Gewissens ist Zurechnung ein Schlüsselbegriff. Am Leitfaden des Zurechnungsbegriffs entsteht ein differenziertes Bild der praktischen Philosophie Kants, das diese auch aus heutiger Sicht attraktiv und tragfähig erscheinen lässt. In systematischer Hinsicht schlägt die Arbeit einen Bogen zu aktuellen Debatten und zeigt, dass Kants Theorie in zentralen Punkten anschlussfähig ist. (shrink)

Aborde la question de l'image chrétienne face à la révolution de la modernité, en montrant comment la nature spécifique de l'image conduit à l'exigence d'un discernement en engageant le spectateur à dépasser ses propres limites. Démontre également que le modernisme de la représentation iconographique n'a rien perdu de son actualité.

BackgroundInstitutions, funding agencies and publishers are placing increasing emphasis on good research data management (RDM). RDM lapses in medical science can result in questionable data and cause the public’s confidence in the scientific community to crumble. A fledgling medical school in a young university in Singapore has mandated every funded research project to have a data management plan (DMP). However, researchers’ adherence to their DMPs was unknown until the school embarked on routine data auditing. We hypothesize that research data auditing (...) improves RDM awareness, compliance and reception in the school.MethodsWe conducted surveys with research PIs and researchers before and after data auditing to evaluate differences in self-reported RDM awareness, compliance and reception. As it is mandatory to deposit research data in a central data repository system in the school, we tracked data deposition by each laboratory from 2 weeks before to 3 months after data auditing as a marker of actual RDM compliance.ResultsResearch data auditing had an overall positive effect on self-reported RDM awareness, compliance and reception for both research PIs and researchers. Research PIs agreed more that RDM was important to scientific reproducibility, were more aware of proper RDM, had higher RDM strength in their laboratories and were more compliant with the DMP. Both research PIs and researchers believed data auditing helped them to be more compliant with data deposition in the repository. However, data auditing had no significant impact on laboratories’ data deposition rates over time, which could be due to the short sampling period.ConclusionsResearch PIs and researchers generally felt that data auditing was effective in improving RDM practices. It helped to evaluate their RDM practices objectively, propose corrective actions for RDM lapses and spread awareness of the university’s data management policies. Our findings corroborated other studies in medical research, geosciences, engineering and ethics that data auditing promotes good RDM practices. Hence, we recommend research institutions worldwide to adopt data auditing as a tool to reinforce research integrity. (shrink)

As systems based on opaque Artificial Intelligence (AI) continue to flourish in diverse real-world applications, understanding these black box models has become paramount. In response, Explainable AI (XAI) has emerged as a field of research with practical and ethical benefits across various domains. This paper not only highlights the advancements in XAI and its application in real-world scenarios but also addresses the ongoing challenges within XAI, emphasizing the need for broader perspectives and collaborative efforts. We bring together experts from diverse (...) fields to identify open problems, striving to synchronize research agendas and accelerate XAI in practical applications. By fostering collaborative discussion and interdisciplinary cooperation, we aim to propel XAI forward, contributing to its continued success. Our goal is to put forward a comprehensive proposal for advancing XAI. To achieve this goal, we present a manifesto of 27 open problems categorized into nine categories. These challenges encapsulate the complexities and nuances of XAI and offer a road map for future research. For each problem, we provide promising research directions in the hope of harnessing the collective intelligence of interested stakeholders. (shrink)

ABSTRACTLaozi is the most translated Chinese text. It has profound philosophical thoughts and is written in a pithy style. It is essential to present its cultural, social, and historical contexts t...

The risks of materials containing nanoscale components are in the public debate discussed as if a manufactured nanomaterial will remain invariant with time and environmental exposure, and as if we can identify its risks by the risks of its nanoscale components. Additionally, the debate on mitigation of specific nanorisks by new legislation implicitly assumes that we can have full and accurate knowledge of the distribution and composition of nanomaterials in a product or the environment. In this discussion note, I argue (...) that physical laws intrinsic to the behavior of nanoparticles both lead to limits on the risks to which we are likely exposed and on our technological ability to verify compliance with new regulations. My conclusion is that governmental actors should be careful not to overreact in their response to a technological revolution that only in few areas is likely to lead to increased public exposure, and in doing so using legal measures for which compliance cannot be monitored. (shrink)

Plant cell culture systems have become an attractive and sustainable approach to produce high‐value and commercially significant metabolites under controlled conditions. Strategies involving elicitor supplementation into plant cell culture media are employed to mimic natural conditions for increasing the metabolite yield. Studies on nanoparticles (NPs) that have investigated elicitation of specialized metabolism have shown the potential of NPs to be a substitute for biotic elicitors such as phytohormones and microbial extracts. Customizable physicochemical characteristics allow the design of monodispersed‐, stimulus‐responsive‐, (...) and hormone‐carrying‐NPs of precise geometries to enhance their elicitation capabilities based on target metabolite/plant cell culture type. We contextualize advances in NP‐mediated elicitation, especially stimulation of specialized metabolic pathways, the underlying mechanisms, impacts on gene regulation, and NP‐associated cytotoxicity. The novelty of the concept lies in unleashing the potential of designer NPs to enhance yield, harness metabolites, and transform nanoelicitation from exploratory investigations to a commercially viable strategy. (shrink)

Nanomaterials have attracted much interest in the medical field and related applications as their distinct properties in the nanorange enable new and improved diagnosis and therapies. Owing to these properties and their potential interactions with the human body and the environment, the impact of nanomaterials on humans and their potential toxicity have been regarded a very significant issue. Consequently, nanomaterials are the subject of a wide range of cutting-edge research efforts in the medical and related fields to thoroughly probe their (...) potential beneficial utilizations and their more negative effects. We posit that the lack of standardization in the field is a serious shortcoming as it has led to the establishment of methods and results that do not ensure sufficient consistency and thus in our view can possibly result in research outputs that are not as robust as they should be. The main aim of this article is to present how NanoDiaRA, a large FP7 European multidisciplinary project that seeks to investigate and develop nanotechnology-based diagnostic systems, has developed and implemented robust, standardized methods to support research practices involving the engineering and manipulation of nanomaterials. First, to contextualize this research, an overview of the measures defined by different regulatory bodies concerning nanosafety is presented. Although these authorities have been very active in the past several years, many questions remain unanswered in our view. Second, a number of national and international projects that attempted to ensure more reliable exchanges of methods and results are discussed. However, the frequent lack of publication of procedures and protocols in research can often be a hindrance for sharing those good practices. Subsequently, the efforts made through NanoDiaRA to introduce standardized methods and techniques to support the development and utilization of nanomaterials are discussed in depth. A series of semi-structured interviews were conducted with the partners of this project, and the interviews were analyzed thematically to highlight the determined efforts of the researchers to standardize their methods. Finally, some recommendations are made toward the setting up of well-defined methods to support the high-quality work of collaborative nanoparticle-based research and development projects and to enhance standardization processes. (shrink)

Much contemporary nanotoxicology, nanotherapeutic and nanoregulatory research has been characterised by a focus on investigating how delivery of engineered nanoparticles (ENPs) to cells is dictated primarily by components of the ENP surface. An alternative model, some implications of which are discussed here, begins with fundamental physicochemical research into the interaction of a dynamic nanoparticle-protein corona (NPC) with biological systems. The proposed new model also requires, however, that any such fresh NPC physicochemical research approach should involve integration and targeted collaboration (...) from the earliest stages with nanotoxicology, nanotherapeutics and nanoregulatory expertise. The justification for this integrated approach, we argue, relates not just to efficiency and promotion of innovation, but to an acknowledgement that public-funded basic physicochemical research in particular should now be accepted to incorporate strong higher order public goods elements from its inception, not merely after product development at the technology transfer stage. Issues, in other words, such as university research co-operation, commercialization and intellectual property (IP) protection, safety and cost-effectiveness regulatory assessment, as well as technology transfer should not be viewed as second tier considerations even in a ‘blue sky’ NPC basic research agenda. (shrink)

Este artigo pretende discutir a interpretação de Heidegger relativamente a como a metafísica tradicional concebeu as noções de “ser” e de “ente”. De fato, conforme o autor, o pensamento ocidental entendido como metafísica confundiu ser e ente. Em seu início com Platão e Aristóteles, no momento em que o problema concernente ao sentido de ser ganhou fôlego no pensamento desses filósofos, esse tema já caiu no esquecimento e o que ambos conquistaram em suas reflexões se quedou trivializado durante toda a (...) história do pensamento ocidental, com muitas deturpações e incompreensões, até a Lógica de Hegel. Em decorrência disso, analisaremos também as consequências dessa posição fundamental, visto que ao não pensar a diferença ontológica, a metafísica tornou-se onto-teo-logia. (shrink)

Osmanlı şer‘iyye sicillerinin bir kısmı Arapça olarak tutulduğu için söz konusu dile hâkim olamayanlar pek yararlanamamaktadırlar. Arapça kayıtlardan istifade etme ve bunların tercümesi ek bir uzmanlık gerektirir. İstanbul kadı sicilleri dahil birkaç örnek dışında bu alanda pek çalışılmamıştır. Bu makalemizde, Arapça siciller üzerinde çalışacaklar için Bursa B-18 numaralı sicilden nitelikli kayıt örnekleri seçilerek günümüz Türkçesi’ne tercüme edilmiştir. Bunun yanında bir kaydın muhteva açısından hangi konuları içerdiğine de değinilmiştir. Ayrıca sicilde yer alan Arapça methiye ve lakaplar da günümüz Türkçesi’ne çevrilmiştir. Sicillerde, (...) Arapça kayıtlar belli bir kalıp içerisinde tutulduğundan, yapılan tercüme örneklerinin, benzer konularda çalışma yapan araştırmacılara kolaylık sağlayacağı düşünülmektedir. (shrink)

El ensayo expone críticamente la fundamentación ontológica de la ética en Antonio Rosmini. Al mismo tiempo, propone una solución al problema de Hume sobre la deducción de proposiciones normativas a partir de las descriptivas. Rosmini parte del análisis del conocimiento. Desde aquí consigue acreditar el paso del pensamiento al ser, distinguiendo tres modos: ser real, ideal y moral. El filósofo identifica el tercero con una estructura agradable en todo lo naturalmente existente. Catalogar esta dimensión ontológica le permite definir el bien (...) universal como el orden amable del ser, y así conectar modernamente con la filosofía antigua. Mediante la contemplación del bien intrínseco de todo ente natural, del orden particular de su esencia, Rosmini puede validar también el salto del ser al deber ser. En efecto, pues del bien propio de cada realidad se desprende una necesidad objetiva, que a su vez aterriza en la constitución intelectiva y volitiva de la persona como necesidad subjetiva. El bien moral consistirá precisamente en el reconocimiento del sujeto de ese bien necesario. (shrink)

El artículo presenta cuatro ejes convergentes para una comprensión integral del Ser del Otro desde una postura ético-crítica. El primer eje lo trata desde la modernidad y la acción comunicativa. El segundo eje lo interroga desde la ciudadanía. El tercer eje se introduce de lleno al Ser del Otro desde la alteridad, presentando la postura ética de Emmanuel Levinas. Finalmente el último eje lo analiza desde la diversidad y la ética de la interculturalidad. Concluye con algunas reflexiones referidas al desafío (...) para la educación de contribuir al rescate del Ser del Otro. (shrink)

En este trabajo nos proponemos primero examinar la concepción marioniana en torno a los nombres divinos, y en particular, su posición con respecto a la elección tomasiana del nombre de “Ser” como “nombre propio” de Dios, en términos de su significado para la filosofía y la teología. En segundo lugar, procuraremos confrontar las tesis de Marion con aquellas que se desprenden de los textos de Tomás, buscando finalmente aportar una respuesta (parcial) al planteo marioniano, a la luz de la doctrina (...) tomasiana de la significación de los nombres. (shrink)

Scientific writings and policy documents define the terms nanomaterial and nanoparticle in various ways. This variation is considered problematic because the absence of a shared definition is understood as potentially hindering nanomaterial knowledge production and regulation. Another view is that the existence of a shared definition may itself cause problems, as rigid definitions arguably exclude important aspects of the studied phenomena. The aim of this paper is to inform this state of disagreement by providing analytical concepts for a systematic understanding (...) of how, and even whether, nanomaterial and nanoparticle could and should be defined. To do this, we review definitions of nanomaterial and nanoparticle presented in research articles and policy documents. Definitions were identified by first conducting a Scopus search and then tracing cited definitions back to their sources. In total, 36 definitions were identified. Theories of definition from philosophy and linguistics provide analytical guidance for structuring and categorizing the identified definitions, and the main analytical dimensions of the definitions are then identified and discussed. Finally, we propose a framework for understanding the process of defining nanomaterial and nanoparticle. This framework considers both the generality needed for a shared understanding and the level of precision required for different purposes. (shrink)

Este artículo discute el problema del ser y el deber ser a la luz de la relación entre lógica deóntica y lógica de normas. Los autores se centran primeramente en las soluciones no-cognoscitivistas de Weinberger y von Wright. Luego de refutar a ambas concepciones por considerarlas fallidas, defienden una concepción no-lingüística de las normas. Según esta última, normar es una especie de acto, norma es el producto de ese acto, y enunciado normativo es la expresión de una norma. | El (...) articulo se publicó en ingles en Archiv für Rechts- und Sozialphilosophie, Vol. LXXIII No. 3, 373–385. Sebastián Figueroa Rubio lo tradujo al español para Revus. (shrink)

«Hermeneutic» means interpretation, that is, looking from a point of view. In this study we try to interpret from the vital reason, the method of Ortega y Gasset, his and his disciple Julián Marías, the Aristotelian concept of «substance». If life is the radical reality, as Ortega stresses, and the person its programmatic realization, in Marías’ opinion, a vital reason of the concept of οὐσία, means to discover its capacity to understand human life. We will find, as a matter of (...) fact, that there are four limits, essentially, that distance the philosopher from that comprehension. By them, we will find the core of the greatest contradictions of the Aristotelian thought, that has been subject to intense critics throughout its history. We will concern, especially, on the function of language in the Greek conception of reason, on the interpretations that brought to «being» and «entity» as Aristotle’s thought starting point «Hermenéutica» significa interpretar, mirar desde un punto de vista. En este estudio buscamos interpretar desde la «razón vital», el método de Ortega y Gasset y su discípulo Julián Marías, el concepto aristotélico de «sustancia». Si la vida es la realidad radical, como afirma Ortega, y la persona es su realización programática, según entiende Marías, una razón vital de la οὐσία significa descubrir su capacidad de comprensión para con la vida humana. Encontraremos, entonces, que hay esencialmente cuatro límites que desvían de esa comprensión; mediante ellos, habremos encontrado el núcleo de importantes contradicciones del pensamiento aristotélico que han sido objeto de encendidos debates a lo largo de la historia. Nos centraremos, sobre todo, en la función del lenguaje en la concepción de la razón griega, en los supuestos interpretativos del «ser» y del «ente» como puntos de partida del pensamiento de Aristóteles . (shrink)

O objetivo deste artigo é responder à questão: a teoria cartesiana das ideias é realista direta ou representacionalista? Para responder a essa questão, analiso as noções de ideia, ser objetivo, realidade objetiva e essência nas "Meditações" de Descartes. Eu procuro mostrar que do ponto de vista da apreensão das essências das coisas externas, Descartes é um realista direto. Mas como algumas provas da existência são inferenciais, eu mostro também que deste ponto de vista a teoria cartesiana é representacionalista. My aim (...) in this article is to answer the question: is the Cartesian Theory of Ideas a direct realist or a representationalist theory? To answer this question, I analyze the notions of idea, objective being, objective reality and essence in Descartes’s "Meditations". I show that, from the point of view of the apprehension of the essences of external things, Descartes is a direct realist. However, since some proofs of the existence are inferential, I also show that, from this standpoint, the Cartesian theory is a representationalist theory. (shrink)

Este trabajo se propone subrayar que la libertad no es sólo predicamental, sino que se inserta en el ser de la persona. En función de esa propuesta, se estudia la doctrina de dos grandes autores, Tomás de Aquino y Nietzsche, parangonando sus formulaciones sobre la existencia y el sentido de la libertad de la persona.

El presente trabajo es un intento por mostrar que la distinción filosófica entre “ser racional” y “uso de razón” subyace a la posición de Francisco de Vitoria y ofrece el fundamento de legitimidad de su desarrollo político-jurídico. El examen filológico de los textos de las Relectiones y el análisis filosóficoconceptual contextualizado han permitido reconstruir argumentos antropológico-filosóficos, epistemológicos y éticos y explicitar, así, un concepto universal de ser humano que, a su vez, se ha revelado como fundamento de un concepto universal (...) de derecho que concierne a todo ser humano, gracias al cual la propuesta vitoriana alcanzaría aceptación y repercusión global. (shrink)

Nous prendrons pour point de départ la célèbre distinction de Winnicott entre un vrai soi et un faux soi ou, en d'autres termes, empruntés à la phénoménologie, entre un soi authentique et un soi inauthentique . Mais le soi est une notion qui ne va pas sans soulever bien des difficultés, y compris aux yeux des spécialistes de l'œuvre de Winnicott, ne serait-ce que dans son rapport au moi. Il nous semble cependant possible d'élucider certaines d'entre elles grâce à l'élaboration (...) par la phénoménologie heideggérienne puis sartrienne des concepts de soi, d'authenticité et d'inauthenticité. En effet, pour Heidegger, le Dasein ne saurait être un moi au sens d'un ego substantiel mais le Dasein est un soi , un être dont le mode d'être est irréductible à celui d'un objet subsistant et qui peut se "choisir" lui-même, se gagner ou bien se perdre . De ce point de vue, l'authenticité est tout d'abord une manière possible d'exister, et si le Dasein peut être soi sur le mode de l'authenticité, il peut l'être également sur le mode privatif de la fuite et de l'inauthenticité. Reprenant le concept heideggérien d'authenticité, Sartre l'enrichit, nous semble-t-il, en insistant sur l'impossibilité pour l'existant d'être ce qu'il est. Ainsi, contrairement au soi inauthentique qui ne cesse de se fuir dans ce qu'on peut appeler un faux soi, le soi authentique ou vrai soi assume son existence et, par conséquent, aussi bien la contingence de son être que sa liberté. Nous essayerons ainsi de montrer qu'il est possible de reprendre et d'approfondir phénoménologiquement la conception winnicottienne du vrai et du faux soi.Partiremos da célebre distinção de Winnicott entre um verdadeiro si-mesmo e um falso si-mesmo ou, em outros termos, emprestados da fenomenologia, entre um si-mesmo autêntico e um si-mesmo inautêntico . Todavia, o si-mesmo é uma noção que levanta muitas dificuldades, também para os especialistas da obra de Winnicott, mesmo que seja somente em sua relação com eu [moi]. Parece-nos possível, entretanto, elucidar algumas dentre essas noções por meio da elaboração da fenomenologia heideggeriana e, em seguida, por meio da sartriana, dos conceitos de si mesmo, de autenticidade e de inautenticidade. Com efeito, para Heidegger, o Dasein não seria um ser, um eu , no sentido de um ego substancial, mas o Dasein é um si-mesmo , um ser cujo modo de ser é irredutível àquele de um objeto subsistente e que pode "escolher" a si mesmo, se ganhar ou mesmo se perder . Desse ponto de vista, a autenticidade é, primeiramente, uma maneira possível de existir, e se o Dasein pode ser si mesmo no modo da autenticidade, ele o pode ser igualmente no modo privativo da fuga e da inautenticidade. Retomando o conceito heideggeriano de autenticidade, Sartre o enriquece, parece-nos, insistindo sobre a impossibilidade para o existente de ser isto que ele é. Assim, contrariamente ao si-mesmo inautêntico que não cessa de fugir para isto que poder-se-ia chamar de falso si-mesmo, o si-mesmo autêntico ou verdadeiro si-mesmo assume sua existência e, por consequência, tanto a contingência de seu ser como sua liberdade. Desse modo, nós tentaremos mostrar que é possível retomar e aprofundar fenomenologicamente a concepção winnicottiana de verdadeiro e falso si-mesmo.We begin with Winnicott's well-known distinction between a true and a false self, or, in terms borrowed from phenomenology, between an authentic and an unauthentic self. Self, however, is a notion that raises many difficulties also for Winnicott scholars, even if only in its relation with the I [me]. Yet it seems possible to elucidate some of those notions by way of a Heideggerian phenomenology followed by a Sartrean phenomenology of the concepts of self, authenticity and unauthenticity. In fact, for Heidegger the Dasein is not a being, an I , in the sense of a substantial ego, but rather a self , a being whose mode of being is irreducible to that of a subsisting object and that can "choose" itself, gain itself , and even loose itself . From this point of view, authenticity is above all a possible mode of existing, and if the Dasein can be itself in the authentic way, it can likewise be in the deprived mode of fleeing and of unauthenticity. Returning to the Heideggerian concept of authenticity, Sartre enriches – it seem to us – by underlining the impossibility for the existent of being what it is. Thus, unlike the unauthentic self that cannot but flee towards that which we might call a false self, the authentic or true self takes on its existence, and therefore also takes on both the contingency of its being and its freedom. Hence, we will try to show that it is possible phenomenologically to resume and go deeper into the Winnicottian conception of the true and false self. (shrink)

Antes de las principales concepciones del Selbstsein, ser-sí-mismo, que anteceden a Heidegger, a saber las de Kiekegaard y Jaspers, en ninguna de ellas entró a tallar decididamente el pensamiento de que el ser-sí-mismo, en cierto modo, se completa como ser-entero (Ganzsein). A propósito de esto, es notable la distinción entre las 2 Secciones de Ser y tiempo, puesto que en la I Sección se tematizó un Dasein, “entre” nacimiento y muerte, y que deja a ambos fuera, en cambio desde el (...) inicio mismo de la II Sección, Heidegger acomete la cuestión de la posibilidad del ser-entero. (shrink)

I discuss the notion of education or educatedness (paideia) involved in the ‘educated human being’ (pepaideumenos), which Aristotle presents at the beginning of his Parts of Animals and a few other passages. The competence of educated human beings makes them able to evaluate some aspects of the explanations in a given domain without having a determinate knowledge about the specific subject-matter in that domain. I examine how such a competence is possible and how it is related to other critical abilities (...) which Aristotle usually ascribes to the science of being qua being. Discuto a noção de educação ou cultura (paideia) envolvida na figura do ser humano cultivado (pepaideumenos), que Aristóteles apresenta no início do tratado As Partes dos Animais e em algumas outras passagens. A competência do ser humano cultivado o habilita a avaliar certo aspecto das explicações propostas em um dado domínio, sem requerer dele um conhecimento determinado sobre o assunto específico do mesmo domínio. Examino de que modo essa competência é possível e como ela se articula a outras habilidades críticas que Aristóteles geralmente associa à ciência do ser enquanto ser. (shrink)

Phosphoinositide (PI) phosphatases such as the SH2 domain‐containing inositol 5‐phosphatases 1/2 (SHIP1 and 2) are important signalling enzymes in human physiopathology. SHIP1/2 interact with a large number of immune and growth factor receptors. Tyrosine phosphorylation of SHIP1/2 has been considered to be the determining regulatory modification. However, here we present a hypothesis, based on recent key publications, highlighting the determining role of Ser/Thr phosphorylation in regulating several key properties of SHIP1/2. Since a subunit of the Ser/Thr phosphatase PP2A has been (...) shown to interact with SHIP2, a putative mechanism for reversing SHIP2 Ser/Thr phosphorylation can be anticipated. PI phosphatases are potential target molecules in human diseases, particularly, but not exclusively, in cancer and diabetes. Therefore, this novel regulatory mechanism deserves further attention in the hunt for discovering novel or complementary therapeutic strategies. This mechanism may be more broadly involved in regulating PI signalling in the case of synaptojanin1 or the phosphatase, tensin homolog, deleted on chromosome TEN.Editor's suggested further reading in BioEssays: Pairing phosphoinositides with calcium ions in endolysosomal dynamics Abstract. (shrink)

O artigo pretende mostrar de que forma Martin Heidegger compreende o modo de ser do Dasein na sua cotidianidade e apresentar os existenciais que possibilitam a superação desse estado, na direção das possibilidades mais próprias. Na cotidianidade, que se caracteriza pela impessoalidade, o que permanece oculto é exatamente o ser-no-mundo, a radical contingência e finitude da existência humana. Angústia, morte, consciência, culpa e resolução, liberados de seu sentido metafísico, deverão poder desocultar tal situação e conduzir o Dasein para o seu (...) modo de ser originário, enfim, para si mesmo. (shrink)

The NANOCAN project aims to enhance our understanding of the behavior of nanomaterials in the body, focusing on biodegradable nanoparticles for cancer diagnostics, and targeted cancer drug delivery. There is a range of available and potentially useful nanoparticles and drugs that might be of interest to such a project. In this paper, we make values implied in—and relevant to—choices between these alternatives explicit, thereby offering a case study of how values enter research processes in this area. From a (...) project centered perspective, we observe that values often play their role implicitly, as a result of funding incentives, regulations, and structural and organizational features of the research process. Based on our observations and categorization of relevant values, we turn to a broader discussion of how responsible research and innovation can be facilitated by making value priorities, value conflicts, and biases explicit targets of normative assessment. (shrink)

Este trabajo tiene por finalidad analizar la pregunta por el sentido de ser como la tarea o quehacer propio de la filosofía, subrayando el carácter específico que dicha pregunta tiene como articuladora del método y de la estructura argumentativa de Ser y tiempo. Se centra en el análisis de la estructura formal de dicha pregunta, particularmente a partir de su tratamiento en el § 2, con la intención de mostrar la plausibilidad de que la reiteración de la pregunta por el (...) sentido de ser es el método desplegado en Ser y tiempo, a partir de lo cual puede proyectarse la articulación argumentativa de la obra en su conjunto. (shrink)

Atacado, celebrado, discutido, interpretado desde las más diversas perspectivas, Ser y Tiempo , que Heidegger publicara en 1927, es, sin duda, uno de los libros más importantes del siglo veinte. A su estudio estuvo dedicado el presente seminario, cuyo objetivo no fue ni la presentación global de esa obra ni un análisis detallado del texto, sino el de ser una introducción a algunos de sus temas fundamentales.