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This paper is concerned with the reappraisal of Husserl’s ontology and epistemology, sketched in book one of Ideen. The main issue is Husserl’s theory of essence and essential insight. I present the fundamental distinction between facts and essences, and, over and above it, Husserl’s defense of an a priori knowledge based on essential insight as well as his partition of the whole realm of a priori knowledge into a formal set of material, regional ontologies. I will show how the theory of essential insight presented in Ideen gives rise to several criticisms, namely those made by Neo-Kantians, like Rickert and Natorp. In the last part, I will show how the mathematical concept of an invariant under a group of variations was the leading case for Husserl’s mature notion of eidetic insight.

In this article, I start with an analysis of Husserl’s description of the intentional structure of communicative intentions in the Logical Investigations, pointing to some obvious shortcomings of it. Then, I stress some important criticisms of Husserl’s approach, namely by Pfänder, and I endeavor to show that Husserl was very close to a full-fledged theory of communicative intentions in the years around 1910. I then turn to Reinach’s theory of social acts, without deciding whether Reinach’s approach was dependent or not on Husserl’s new views concerning the intentionality of communicative acts. Regarding Reinach’s theory of the Vernehmung, I criticize a widespread trend to construe (and translate) it as something like a perception (Wahrnehmung), showing that it expresses what I call the “vocative element” of the communicative acts. Then, I point to some complements that Reinach’s description is in need, and I finish with an outline of a phenomenologically oriented concept of communication, based on Husserl’s and Reinach’s insights.

Nous commençons par souligner les trois innovations kantiennes qui mettent la philosophie théorique sur une nouvelle voie. Premièrement, une nouvelle forme de la Philosophie théorique, présentée non plus comme une théorie directe de la nature, mais comme une enquête réflexive de la science mathématique de la Nature comme un fait primitif. Deuxièmement, la méthode transcendantale, comme détermination réflexive-régressive des conditions subjectives de possibilité de la connaissance des objets en général. Troisièmement, le rôle central joué par la science newtonienne de la nature. Après cela, je discute de la réévaluation logico-positiviste du récit de Kant à la lumière de la relativité générale d'Einstein et de la réplique de Cassirer, soulignant avec ce dernier la nécessité d'une révision des thèses de Kant sur l'espace, sans toutefois abandonner la posture transcendantale kantienne et sa théorie de la constitution de quelque chose comme objet de connaissance. Enfin, nous concluons par quelques remarques qui visent à une esthétique transcendantale renouvelée qui serait capable d’absorber la théorie de l’espace-temps que la physique d’Einstein a mise en avant., Começo enfatizando as três inovações kantianas que colocam a filosofia teórica em um novo caminho. Em primeiro lugar, uma nova forma para a Filosofia teórica, apresentada não mais como uma teoria direta da natureza, mas como uma investigação reflexiva da ciência matemática da Natureza como um fato primitivo. Em segundo lugar, o método transcendental, como determinação reflexivo-regressiva das condições subjetivas de possibilidade do conhecimento dos objetos em geral. Em terceiro lugar, o papel central desempenhado pela ciência newtoniana da natureza. Em seguida, discuto a reavaliação lógico-positivista do relato de Kant a luz da relatividade geral de Einstein e da réplica de Cassirer, enfatizando com este último a necessidade de uma revisão das teses de Kant sobre o espaço, sem abandonar, no entanto, a postura transcendental kantiana e sua teoria da constituição de algo como objeto de conhecimento. Por fim, concluo com algumas observações que visam uma estética transcendental renovada que seria capaz de absorver a teoria do espaço-tempo que a física de Einstein propôs.

In this paper, I discuss the possible relations between Fritz London’s account of the status of the observer in quantum physics and transcendental phenomenology. Firstly, I discuss Steven French’s interpretation of London’s thesis as a phenomenological account of the status of the observer, along with the objections Otavio Bueno has brought forward. Secondly, refusing in part both French’s and Bueno’s theses for several reasons, I propose another way of reading London’s thesis in the framework of transcendental phenomenology. Namely, I put London’s account of the observer against the backdrop of Husserl’s analyses of the objectifying acts and objectual constitution. Finally, I end this article with some criticisms of what seems to me the ontological indigency of the Copenhagen interpretation of quantum physics, to whose “spirit” London also belongs.

I offer an outline of an integrated phenomenological analysis of free fantasy and of fictional worlds. My main concern amounts to stress the scissions entailed in free fantasy and in the consciousness of fictional objects: a scission of the I, and a scission of the experience. Firstly, I offer a somewhat new characterization of the presence of the objects of free fantasy, which disconnects any possible relationship of those objects with a real perception as the leading form of an originally giving consciousness. My leading example is daydream. Secondly, I take the Husserlian analysis of neutralization as a conceptual tool to explain the consciousness of fictional worlds, against a new tendency for interpreting these worlds in light of the concept of “possible world”. The two approaches converge to a twofold characterization of the mode of being of fictions and of the modality of presence of the objects of fantasy.

The chapter has two parts. In the first part, I introduce a more fine-grained analysis of evaluative sentences. I distinguish between evaluations proper and directions for action with several degrees of constraint: commands, pieces of advice, suggestions, and so on. I call the latter “ductive-statements.” Thus, I affirm that the realm of morals has two branches: one relative to evaluations, which are is-sentences ranging from the several degrees between good and bad to the indifferent (adiaphoron); the other relative to sentences having a “ductive” force (do-statements) that impose, with different degrees of coercion, a course of action. In the second part of the chapter, I address Searle’s famous argument concerning the derivation of ought-sentences from is-sentences. Relying on my previous distinctions, I argue that Searle’s derivation is flawed in two main points, which I present and discuss at length.

In what follows, I intend to address an issue which is at the boundaries of the phenomenological method of reflective explication, and that, in this sense, points to some limitations of the phenomenological approach to consciousness and mind. I am referring to an aporetic situation that is at the heart of the phenomenological analysis of passivity. On the one hand, phenomenology shows, at least indirectly, a passive life that is beyond the first steps of the activity of the ego in the receptive, affective life. This is something that is beyond the rising of an ego, and from which a phenomenology of the ego-form of subjective life could be addressed. On the other hand, the analytic and conceptual tools of the phenomenological method have no grips on this basic realm of subjective life. As a result, Husserl’s analysis of passivity starts with the evidence of a pre-affective, pre-egoic realm, from which a phenomenology of the ego could be developed. However, Husserl’s analyses end up with the denegation of this dimension, as if it was invisible for the phenomenological method. As a consequence, the starting point of the analysis is not passivity proper, but rather the primitive forms of receptivity, which is already a first layer of the activity of the ego. Instead of an analysis of the ego-polarization (the “birth” of the ego), the egoic layer of conscious life is simply presupposed. A phenomenology of the ego-form is, thus, at the same time promised and denied. This aporetic situation is visible in the alteration of the concept of a passive pre-givenness in Husserl’s Analysis Concerning Passive Synthesis.

En este artículo, examino algunas características importantes de las teorías de conciencia y autoconciencia de Brentano y Rosenthal. En particular, analizo la distinción entre estados mentales y estados conscientes, y la cuestión relacionada con de determinar si todos los estados mentales pueden convertirse en estados conscientes. Interpreto la teoría de Brentano como una teoría de la mente de un nivel que está de acuerdo con la fusión cartesiana entre los estados mentales y la conciencia. Argumento que los problemas que surgen de la posición de Brentano son, hasta cierto punto, superados por una teoría de orden superior, de modo que la posición de Rosenthal es más precisa. Sin embargo, estoy en desacuerdo con ambos en la interpretación de la consciencia de un estado mental como autoconciencia. Desarrollo los fundamentos de una teoría basada en la primacía del organismo y su mundo vital, y de la experiencia consciente como la forma superior de la vida mental, que tiene, sin embargo, sus raíces en la compleja red de estados mentales que son no estados conscientes.In this paper, I examine some important features of Brentano’s and Rosenthal’s theories of consciousness and self-consciousness. In particular, I discuss the distinction between mental states and conscious states, and the related question of determining whether all mental states can become conscious states. I interpret Brentano’s theory as a one-level theory of mind which is in keeping with the Cartesian conflation between mental states and conscious-ness. I argue that the problems arising from Brentano’s position are to a certain extent surpassed by a higher-order theory, so that Rosenthal’s position is more accurate. Nevertheless, I disagree with both in the construal of the consciousness of a mental state as self-consciousness. I develop then the fundamentals for a theory based on the primacy of the organism and its vital world, and of conscious experience as the higher form of mental life, which has, however, its roots in the complex net of mental states which are not conscious states.

Purpose: Characterization of tumor antigen–specific CD4 T-cell responses in healthy donors and malignant melanoma patients using an in vitro amplified T-cell library screening procedure. Patients and Methods: A high-throughput, human leukocyte antigen (HLA)-independent approach was used to estimate at unprecedented high sensitivity level precursor frequencies of tumor antigen- and neoantigen-specific CD4 T cells in healthy donors and patients with cancer. Frequency estimation was combined with isolation and functional characterization of identified tumor-reactive CD4 T-cell clones. Results: In healthy donors, we report frequencies of naïve tumor-associated antigen (TAA)-specific CD4 T cells comparable with those of CD4 T cells specific for infectious agents (Tetanus toxoid). Interestingly, we also identified low, but consistent numbers of memory CD4 T cells specific for several TAAs. In patients with melanoma, low frequencies of circulating TAA-specific CD4 T cells were detected that increased after peptide-based immunotherapy. Such antitumor TAA-specific CD4 T-cell responses were also detectable within the tumor-infiltrated tissues. TAA-specific CD4 T cells in patients displayed a highly polyfunctional state, with partial skewing to Type-2 polarization. Finally, we report the applicability of this approach to the detection and amplification of neoantigen-specific CD4 T cells. Conclusions: This simple, noninvasive, high-throughput screening of tumor- and neoantigen-specific CD4 T cells requires little biologic material, is HLA class II independent and allows the concomitant screening for a large number of tumor antigens of interest, including neoantigens. This approach will facilitate the immunomonitoring of preexisting and therapy-induced CD4 T-cell responses, and accelerate the development of CD4 T-cell–based therapies.

Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute promising targets for the development of T cell vaccines. Whereas CT antigens are frequently expressed in melanoma, their expression in colorectal cancers (CRC) remains poorly characterized. Here, we have studied the expression of the CT antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC because of the presence of well-described HLA-A2-restricted epitopes in their sequences. Our analyses of 41 primary CRC and 14 metastatic liver lesions confirmed the low frequency of expression of these CT antigens. No increased expression frequencies were observed in metastatic tumors compared to primary tumors. Histological analyses of CRC samples revealed heterogeneous expression of individual CT antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8(+) T cell response could be demonstrated. These results show that the expression of CT antigens in a subset of CRC patients induces readily detectable T cell responses.

Discussing from a phenomenological stance the distinction between hyletic and expressive conceptions of norms, I stress that phenomenology is able to develop an analysis of nomothetic intentionality that can surmount the opposition presented by Alchourrón and Bulygin. However, this entails a revision of the Husserlian analysis of the relationship between judgments and norms, namely of his thesis concerning the foundation of every intentional act in objectifying acts. I highlight the specificity of normative intentionality, its non-dependence on objectifying acts, and I propose to name the quality of normative acts as “ductive force”. Then, I take distance to the classical analysis of normative judgments as having the ought-form, outlining a more detailed analysis of them, namely stressing that the juridical propositions must have a richer content in order to describe norms. Then, I propose my own account based on the concept of “ductive force”. I affirm that the ductive force of norms cannot be identified only with coercion. I show that there is, even inside the juridical sphere, a variety of ductive forces, going from sheer coercion to council and recommendation. Finally, I stress the centrality of the concept of “ductive force” for a phenomenology of the social world.

I examine the Kantian concept of a transcendental logic, stressing its novelty and richness. I discuss the relationship between logical form of judgments and pure concept of the understanding, trying to elucidate how the pure concept Is embedded in the form of judgments. Exploring this issue, I construe transcendental logic as a part of formal ontology, pointing at the end of the article to some limitations that hinder the Kantian concept of a formal theory of the “object In general”.

In this paper, I discuss several issues about space. Namely, how Kant comes to a comprehension of space that affirms both its ideal and absolute character; how, following Husserl, the space representation relates to the sphere of formal essences that redefines geometry as a theory of abstract manifolds; how the continuity of space interferes in the constitution of the physical thing in the framework of Husserlian phenomenology, and, finally, the results of a supposedly regress to an original dimension of space, as proposed by Heidegger.

I sketch an analysis of observing as a particular attitude one can take regarding the surrounding world. I stress some particular features of observation, like the cancelling of the vital engagement. in the world, and the delight that pure observation involves. Then I move to a description of figurative consciousness and its image-world. In the final part, 1 try to show how watching movies displays a new type of observation, based on the empathic connection with the characters, the emergence of a virtual body, and a self-decentered life, where the ego is not an onlooker, but something like an “ in-looker”.

While not a phenomenologist, Fernando Gil was highly interested in some aspects of Husserl’s work. One of these aspects was Husserl’s theory of evidence. ln a notable book entitled Traité de l’évidence, he developed a throughout theory of evidence, paying close attention to the most important insights Husserl exposed his works. Gil’s theory of evidence is at the same time rooted in Phenomenology and extended beyond it in as much as he locates the first dimension of evidence ma primitive stratum hallucinating aesthesia from desire. Accounting for evidence as threefold process, going from aesthesia to presence, and then to the intellectual grasping of an individual object, the most interesting feature of his theory is the of evidence as a hallucinating process, encompassing all strata of sensitive, perceptive, and conceptual life.

In this paper, I present the main traits of the phenomenological thinking of Abranches de Soveral. I start with the work of his master Miranda Barbosa explaining the criticisms he address to the Husserlian phenomenology. I show Soveral’s approach to phenomenology is framed by the conceptions of Barbosa and the problems that, for him, phenomenology cannot answer in an accurate way. In this context, I present the fundamental tenets of Soveral’s rejoinder to his master, showing how phenomenology can be rearranged in order to formulate and to answer “the fundamental problem of knowledge”.

Gustavo de Fraga was one of the most influential Portuguese phenomenologists. He had a deep understanding of the Husserlian as well as of the Heideggerian phenomenology. One of his major concerns was the connection between these thinkers, and the resettlement of metaphysical questions some step beyond the works of both. In so doing, Gustavo de Fraga took an original stance in the field of Phenomenology, combining conceptual and poetic experiences of thought.

Berkeley’s general tenet about immaterialism is presented and discussed. I examined apart the several theses that concur to the immaterialist theory. After that, the general argument is presented and discussed. In particular, I stress Berkeley’s assumption that a world without matter and a world with matter would be indistinguishable from the point of view of (i) the content of perceptions, (ii) natural science (viz. Newtonian mechanics). I stress that this assumption depends on a relative account of circular motion, generating the centrifugal forces, as Newton shows in his bucket experiment. In spite of the efforts by Leibniz and Huygens, such a relative account of rotational motion was never presented. So the thesis about the scientific and perceptual identity between worlds with and without matter remains a simple case of wishful thinking in need for a justification.

In this paper I discuss Berkeley’s theories about vision, perception of distance, and the foundations of Geometry. I start with Locke’s answer to Molineaux’s problem and the criticisms Berkeley addressed to it. I explain the fundamentais of Berkeley’s theory about our cognitive shaping of the visual field and the type of connections that visual data establishes with data from the haptic field. I show how interesting are Berkeley’s conceptions for a phenomenology of perception, and, eventually, I carried some phenomenological evidence against Berkeley’s too much strict location of the idea of distance in the haptic field alone.

I discuss Husserl’s concept of norm, and its relevance for a phenomenology of practical reason. I confront Husserl with Wilhelm Wundt, Hans Kelsen, and Carl Schmitt about, respectively, what a norm is, about the relation between theoretical and normative sciences, and, finally, about the creation of political concepts within European culture. In the last section, I develop some theoretical insights about the constitutive character of normative consciousness, abandoning Searle’s distinction between constitutive and regulative rules. I stress also the importance of a phenomenology of plural and collective subjectivity in order to develop a phenomenological theory of state and normative experience.

I intend to understand from a phenomenological point of view the relationship between figurative consciousnesses (Bildbewusstsein) and other non-original presentations (Vergegenwiirtigungen) such as expectations, recollections or fantasies. I centre my analyses in the difference between figurative consciousness, on the one hand, and a modality of fantasy I cal! “daydream consciousness”, on the other. I stress that figurative consciousness implies apure observational ego, whereas day-dream consciousness is a free construction of the ego’s own personal story. The freedom of”day dream consciousness” has, nevertheless, some important constraints. I emphasize the constraints that come from the passive and affective life of the ego. Finally, I propose new criteria for the phenomenological differentiation between the several kinds of acts of non-original presentation.

In this paper I discuss the consistency and accuracy of Husserl’s sketch of a theory about non-declarative sentences in the last chapter of Logical Investigations. Whereas the consistency is acknowledged, the accuracy is denied, because Husserl’s treatment of non-declarative phrases such as questions or orders implies that those phrases contain, in some way, a declarative sentence and an objectifying act. To construct a question like “is A B?” as being equivalent to a pseudo-declarative sentence such as “I ask whether A is B” is, however, a false phenomenological analysis, because to ask o r to order or to beg is not to assert. I turn, then, to John Austin ‘s theory of performative (as opposed to constatative) utterances and illocutionary acts in order to find a more accurate approach to the logical-semantic content of non-declarative sentences. Eventually, I show how this Husserlian theory of non-declarative sentences has a negative impact on the phenomenological theory of social ·acts and communication.

In this paper, I start with the opposition between the Husserlian project of a phenomenology of the experience of time, started in 1905, and the mathematical and physical theory of time as it comes out of Einstein’s special theory of relativity in the same year. Although the contrast between the two approaches is apparent, my aim is to show that the original program of Husserl’s time theory is the constitution of an objective time and a time of the world, starting from the intuitive giveness of time, i.e., from time as it appears. To show this, I stress the structural similarity between Husserl’s original question of time and the problem of a phenomenology of space constitution as it was first developed in the his manuscripts from the nineteenth century, in which we find the threefold question of the origin of our representation of space, of the geometrization of intuitive space, and of the constitution of transcendent world space. Finally, I reconsider some of Husserl’s main theses about the phenomenological constitution of objective time in light of the main results of special relativity time-theory, introducing several corrections to central assumptions that underlie Husserl’s theory of time.

Childbirth is one of the most important experiences in the world of life, which women and their families have experienced for a long time without the intervention of techniques and without the presence of people who were not part of their world. The technical and scientific reasons inherent in the field of labor and birth began to occupy the space of the objectification of the world's facts and rationality started to prevail. Moving back to the origins of the technicalization of childbirth care, this article intends to discuss the reduction of labor to a clinical process focused on its purely biological dimension. Its inspiring base is Husserl's phenomenological philosophy, the mathematization of nature and technicalization of our relationship with the world, in order to expand perspectives beyond the health techniques, understand intersubjectivity and rescue human dignity. RESUMEN El parto se constituye como una de las experiencias más importantes en el mundo de la vida, vivido por mucho tiempo, por las mujeres y sus familias sin la intervención de técnicas y de la presencia de personas que no hacían parte de su mundo. Las razones técnicas y científicas inherentes al ámbito del parto y nacimiento comenzaron a ocupar el espacio de la objetivación de los hechos del mundo y la racionalidad empezó a prevalecer. Retrocediendo a los orígenes de la tecnificación de la práctica del cuidado al parto, este artículo se propone a reflexionar sobre la reducción del parto a un proceso clínico centrado en la pura dimensión biológica. Tiene como base la filosofía fenomenológica de Husserl, la matematización de la naturaleza y la tecnificación de nuestra relación con el mundo. Esto con el objetivo de ampliar las perspectivas más allá de las técnicas en salud, comprender la intersubjetividad y rescatar la dignidad humana. RESUMO O parto constitui-se como uma das mais importantes experiências no mundo da vida, vivenciado, por muito tempo, pelas mulheres e suas famílias sem a intervenção de técnicas e a presença de pessoas que não faziam parte do seu mundo. As razões técnica e científica inerentes ao campo do parto e nascimento passaram a ocupar o espaço da objetivação dos fatos do mundo e a racionalidade passou a predominar. Recuando até as origens da tecnicização da prática do cuidado ao parto, este texto pretende refletir acerca do parto como um processo clínico centrado sobre sua pura dimensão biológica. Tem como base inspiradora a filosofia fenomenológica, de Husserl, a matematização da natureza e a tecnicização de nossa relação com o mundo. Para ampliar o olhar para além das técnicas em saúde, compreender a intersubjetividade e resgatar a dignidade humana.

Carcinoembryonic antigen (CEACAM5) is commonly overexpressed in human colon cancer. Several antigenic peptides recognized by cytolytic CD8+ T-cells have been identified and used in colon cancer phase-I vaccination clinical trials. The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line. However, the immunogenicity of this peptide in humans remains unknown. We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors. Immunogenic-altered peptide ligands with increased affinity for HLA-A*0201 were identified. Importantly, the elicited cytolytic T lymphocyte (CTL) lines and clones cross-reacted with the wild-type CEA(694-702) peptide. Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition. Finally, CEA-specific T-cell precursors could be readily expanded by in vitro stimulation of peripheral blood mononuclear cell (PBMC) from colon cancer patients with altered CEA peptide. However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition. Together, using T-cells to demonstrate the processing and presentation of the peptide CEA694-702, we were able to corroborate its presentation by tumor cells. However, the low avidity of the specific CTLs generated from cancer patients as well as the high-antigen expression levels required for CTL recognition pose serious concerns for the use of CEA694-702 in cancer immunotherapy.

In this paper, I start with the opposition between the husserlian project of a phenomenology of the experience of time, started in 1905, and the mathematical and physical theory of time, as it comes out from the special theory of relativity, by Einstein, in the same year. Although the contrast between the two approaches is apparent, my aim is to show that the original program of Husserl’s time theory is the constitution of an objective time and a time of the world, starting from the intuitive giveness of time, i.e., from time as it appears. To show this, I stress the structural similarity between the original question of time, by Husserl, and the problem of a phenomenology of the space constitution, as it was first developed in the husserlian manuscripts of the XIX century, in which we find the threefold question of the origin of our space representation, of the geometrization of intuitive space and the constitution of transcendent world space. Finally, I reconsider some of Husserl’s main theses about the phenomenological constitution of objective time in the light of the main results of special relativity time-theory, introducing several corrections to central assumptions that underlie Husserl’s theory of time.

espanolEn este articulo, examino la teoria del conflicto de Sartre. Esta es la tesis fundamental de Sartre en lo que se refire a la descripcion fenomenologica de las relaciones interpersonales. Dando enfasis en las influencias de Hegel y Husserl sobre Sartre, sigo la evolucion de la tesis sartreana desde La Transcendance de l’Ego hasta L’Etre et le Neant. El articulo apresenta algunos de los problemas de la Teoria del Conflicto de Sartre. En primer lugar tenemos el problema de la manera como Sartre foca sus descripciones en la relacion de uno a otro. En segundo lugar, tenemos el problema de la descripcion de la consciencia de un alter-ego como una consciencia de si o autoconsciencia (la consciencia de un alter-ego es, para Sartre, lo mismo que la consciencia de si-mismo como un “serpara- el-otro”). El texto finda con la apreciacion negativa de la tesis de Sartre. EnglishIn this paper, I examine conflict theory as the fundamental thesis of Sartre’s phenomenological description of interpersonal relationships. I stress Sartre’s debts toward Hegel and Husserl, and I follow his evolution from La transcendance de l’ego till L’etre et le neant. I intend to show several problems in Sartre’s conflict thesis. First, there is a problem regarding the way Sartre focuses his descriptions exclusively on the face-to-face relationship. Second, there is another problem regarding Sartre’s attempt to describe the relation to an alter ego as a kind of self-consciousness (consciousness of an alter ego is the same as self-consciousness as a “being-for-other”), instead of a direct intention in the pre-reflexive area. I finish with a negative appraisal of Sartre’s thesis. portuguesNeste artigo, examino a teoria sartreana do conflito. Ela e a tese fundamental de Sartre no que se refere a descricao fenomenologica das relacoes interpessoais. Sublinho as dividas de Sartre relativamente a Hegel e a Husserl, e sigo a evolucao da tese sartreana desde La Transcendance de l’Ego ate L’Etre et le Neant. O artigo procura mostrar alguns dos problemas da Teoria do Conflito de Sartre. Primeiramente, ha um problema no que diz respeito a maneira como Sartre focaliza suas descricoes exclusivamente no relacionamento “face-a-face”. Em segundo lugar, ha um outro problema no modo como Sartre tenta descrever a consciencia de um alter-ego como um tipo de consciencia de si ou de autoconsciencia (a consciencia de um alter-ego e, para Sartre, o mesmo que a consciencia de si proprio como um “ser-para-o-outrem”), em vez de uma intencao direta no plano pre-reflexivo. Termino com uma apreciacao negativa da tese de Sartre.

One of the challenges of tumour immunology remains the identification of strongly immunogenic tumour antigens for vaccination. Reverse immunology, that is, the procedure to predict and identify immunogenic peptides from the sequence of a gene product of interest, has been postulated to be a particularly efficient, high-throughput approach for tumour antigen discovery. Over one decade after this concept was born, we discuss the reverse immunology approach in terms of costs and efficacy: data mining with bioinformatic algorithms, molecular methods to identify tumour-specific transcripts, prediction and determination of proteasomal cleavage sites, peptide-binding prediction to HLA molecules and experimental validation, assessment of the in vitro and in vivo immunogenic potential of selected peptide antigens, isolation of specific cytolytic T lymphocyte clones and final validation in functional assays of tumour cell recognition. We conclude that the overall low sensitivity and yield of every prediction step often requires a compensatory up-scaling of the initial number of candidate sequences to be screened, rendering reverse immunology an unexpectedly complex approach.

STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8(+) T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP(86-94) and STEAP(262-270)). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201(+) STEAP(+) human tumor cells. Furthermore, STEAP(86-94) and STEAP(262-270) stimulated specific CD8(+) T cells from HLA-A*0201(+) healthy donors, and these peptide specific CD8(+) T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP(86-94)-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8(+) T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy.

Human Ag-specific CD8+ T lymphocytes are heterogeneous and include functionally distinct populations. In this study, we report that at least two distinct mechanisms control the expansion of circulating naive, memory, and effector CD8+ T lymphocytes when exposed to mitogen or Ag stimulation. The first one leads to apoptosis and occurs shortly after in vitro stimulation. Susceptibility to cell death is prominent among primed T cell subsets, and it is inversely correlated with the size of the ex vivo Bcl-2high population within these subsets. Importantly, the Bcl-2high phenotype is associated to the proportion of responsive CD8+ T cells, independently of their differentiation stage. The second one depends on the expression of newly synthesized cyclin-dependent kinase inhibitor p16INK4a that occurs in a significant fraction of T cells that had been actively cycling, leading to their cell cycle arrest upon stimulation. Strikingly, accumulation of p16INK4a protein preferentially occurs in naive as opposed to primed derived T lymphocytes and is not related to apoptosis. Significant levels of p16 are readily detectable in a small number of ex vivo CD8+ T cells. Our observations reveal that activation-induced p16 expression represents an alternative process to apoptosis, limiting the proliferation potential of activated naive derived T lymphocytes.

The design of a broad application tumor vaccine requires the identification of tumor antigens expressed in a majority of tumors of various origins. We questioned whether the major stress-inducible heat shock protein Hsp70 (also known as Hsp72), a protein frequently overexpressed in human tumors of various histological origins, but not in most physiological normal tissues, constitutes a tumor antigen. We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201. These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner. Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients. Hsp70 is a tumor antigen and the Hsp70-derived peptides p391 and p393 could be used to raise a cytotoxic response against tumors of various origins. © 2003 Wiley-Liss, Inc.

Parathyroid hormone-related protein (PTH-rP), a secreted protein produced by prostate carcinoma and other epithelial cancers, is considered a key agent for the development of bone metastases. We investigated the construct GC90/IRIV, composed of immunopotentiating reconstituted influenza virosomes (IRIV) containing PTH-rP gene plasmids (GC90), as a potential tool for human anticancer immunotherapy into humanised mice transgenic for HLA-A(*)02.01, the human-beta2 microglobulin, and the human CD8alpha molecule. Intranasal administration of GC90/IRIV resulted in the induction of a PTH-rP-specific multiepitope cytotoxic T-cell (CTL) response. Cytotoxic T cells derived from vaccinated mice were capable of lysing in vitro syngenic murine PTH-rP transfectants and human HLA-A((*))02.01(+)/PTH-rP(+) prostate carcinoma LNCaP cells as well. The immune response capacity and the absence of any sign of toxicity and/or autoimmunity in vivo suggest the GC90/IRIV vaccine as a valid tool for active specific immunotherapy of human cancers and metastases overexpressing PTH-rP.

DOI: http://dx.doi.org/10.12957/ek.2014.15183 O artigo pretende discutir a relacao entre os conceitos de intencionalidade e autoconsciencia na tradicao fenomenologica. Para tanto, apresenta e debate tais conceitos a partir da obra de Brentano, Husserl e Sartre. A tese do artigo consiste em mostrar que boa parte da tradicao fenomenologica tratou o problema da relacao entre intencionalidade e autoconsciencia seguindo a tese de matriz brentaniana que pode ser denominada modelo conjuntivo . Contudo, o autor propoe que exista uma outra possibilidade de se pensar tal relacao, a partir do que ele denomina modelo projetivo da autoconsciencia. Tal modelo pode ser explorado seguindo caminhos abertos pela filosofia husserliana.

In the first part of this paper we try to show how the discussion of Meinong’s distinction between distributed and undistributed objects was crucial for Husserl’s thinking about the phenomenology of time consciousness. The criticism of Meinong’s thesis that the representation of a distributed object (temporal object) is an undistributed act is presented as the central point for the development of Husserl’s own thesis about the perception as a continuum of continua and about consciousness as an unitary flux of temporal phases. In a second part, we move to Brentano’s theory about original associations in the constitution of the “presence-time”. Brentano’s position about the function of phantasy as the origin of our representation of time is refused by Husserl and, as a result, the structural composition of time consciousness in phases of primal-impression, fresh memory (later “retention”) and immediate expectation (later “protention”) appears as the core form to the intuition of the present and the constitution of time. In a last section, we follow Husserl’s revision of his own analysis of fresh memory in order to understand his final position about retention as a primitive form of Vergegenwärtigung.

Mucins are high-molecular-mass glycoproteins with high carbohydrate content and marked heterogeneity both in the apoprotein and in the oligosaccharide side chains. Mucin genes are expressed in a regulated manner, namely in the human stomach. The first aim of the present study was to characterise the expression of mucins and mucin-associated carbohydrate antigens in seven gastric carcinoma cell lines, and to compare their expression profiles with those of normal gastric tissues and human gastric carcinomas. Secondly, we aimed to see whether or not there is an association between the expression of mucins and mucin-associated carbohydrate antigens. Our results show that mucin expression in gastric carcinoma cell lines: (a) follows in part the mucin expression profile of normal gastric mucosa and gastric carcinomas with wide expression of MUC1 and MUC5AC; (b) parallels the aberrant pattern of mucin expression observed in human gastric carcinomas with occasional expression of MUC2, MUC3, MUC4 and MUC5B; (c) does not include, at least in our series, the expression of MUC6 mucin; and (d) follows in part the differentiation pattern of the carcinomas from which the cell lines originated, keeping S-Tn expression in cell lines derived from glandular carcinomas. Our results further demonstrate that there is no apparent relationship between the mucin core proteins and the simple mucin-type or Lewis carbohydrate antigens.