54 research outputs found

    NETTAB 2012 on “Integrated Bio-Search”

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    The NETTAB 2012 workshop, held in Como on November 14-16, 2012, was devoted to "Integrated Bio-Search", that is to technologies, methods, architectures, systems and applications for searching, retrieving, integrating and analyzing data, information, and knowledge with the aim of answering complex bio-medical-molecular questions, i.e. some of the most challenging issues in bioinformatics today. It brought together about 80 researchers working in the field of Bioinformatics, Computational Biology, Biology, Computer Science and Engineering. More than 50 scientific contributions, including keynote and tutorial talks, oral communications, posters and software demonstrations, were presented at the workshop. This preface provides a brief overview of the workshop and shortly introduces the peer-reviewed manuscripts that were accepted for publication in this Supplement

    NOTCH3 Expression Is Linked to Breast Cancer Seeding and Distant Metastasis

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    Background: Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods: We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results: In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions: These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer

    Phenomenal Deformations: Affordance as a Design Tool to Deal with Subject-Object Complementarity in Architecture

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    The production of knowledge related to the architectural project during the design phase mainly concerns the object in itself, while its relationship with occupants is an underrated factor for design success. This is due to the fact that architecture as a formal design field is naturally devoted to deal with the physical and geometric characteristics of the design object identified in unequivocal ways, while occupancy implies a degree of subjectivity and contingency which phenomenally deforms the object into its many manifestations. This paper analyses the concept of affordance by Gibson (1979) as a suitable tool to deal with occupancy in terms of subject-object complementarity because it addresses the ecological value of an object, i.e. its value in relation to a perceiving subject and not in itself. The first problems posed by the concept of affordance, hence, is how the subject can be identified given the variety of real occupants which interact with a certain environment. The answer usually is to address only those aspects which are in common between all the subjects, i.e. the ones which define occupants as members of a species. At this level, indeed, occupants are natural subjects, who can only express basic needs to be met by sensorimotor activities, and for this reason a different approach considering the subject as culturally and also individually defined is needed in order to shift from an automatism of inhabitation to the self-determination of occupancy. Affordance must therefore be considered in a broader context going beyond sensorimotor activities and dealing also with upper cognitive faculties. However, an affordance related to a culturally-defined subject does not entail self-determination per se, since also cultural and individual schemes can be absorbed without the exercise of critique due to habituation. Activities driven by natural, cultural or individual schemes differ with regard to the interval they entail between the action received by the environment and subject's reaction. Indeed, more individuality is implied, longer the time needed to process data received from the environment. Time is here intended not as an extensive but as an intensive dimension. This means that it cannot be considered as a sum of instants, but an unitary event having a specific character. This is the concept of duration in Bergson, as opposed to spatialized time, and it also recalls Bakhtin's idea of chronotope. In the overall framework interweaving design activity and time through cognition, chronotopes can be useful in the definition of an affordance-based architectural approach. Indeed some chronotopes describing duration in its becoming are related to the contingent and direct relationship between the subject and his object which is expressed by the concept of affordance. The present paper aims at understanding how these contributions from cognitive sciences, literature, philosophy and semiotics can allow architects to improve affordance as a design tool starting from a review of the state of the art. At the end, some case studies from the past which address the question of a self-determined occupancy are proposed as exemplary of an affordance-based approach to architecture

    Phenomenal Deformations: Affordance as an Architectural Design Tool to Deal with Subject-Object Complementarity in Occupancy

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    Ponència presentada a la sessió 4The production of knowledge related to the architectural project during the design phase mainly concerns the object in itself, while its relationship with occupants is an underrated factor for design success. This is due to the fact that architecture as a formal design field is naturally devoted to deal with the physical and geometric characteristics of the design object identified in unequivocal ways, while occupancy implies a degree of subjectivity and contingency which phenomenally deforms the object into its many manifestations. This paper analyses the concept of affordance by Gibson (1979) as a suitable tool to deal with occupancy in terms of subject-object complementarity because it addresses the ecological value of an object, i.e. its value in relation to a perceiving subject and not in itself. The first problems posed by the concept of affordance, hence, is how the subject can be identified given the variety of real occupants which interact with a certain environment. The common answer is to address only those aspects which are in common between all the subjects, i.e. the ones who define occupants as members of a species. At this level, indeed, occupants are natural subjects, which can only express basic needs to be met by sensorimotor activities, and for this reason a different approach considering the subject as culturally and also individually defined is needed in order to shift from an automatism of inhabitation to the self-determination of occupancy. Affordance must therefore be considered in a broader context going beyond sensorimotor activities and dealing also with upper cognitive faculties. However, an affordance related to a culturally-defined subject does not entail self-determination per se, since also cultural and individual schemes can be absorbed without the exercise of critique due to habituation. Activities driven by natural, cultural or individual schemes differ with regard to the interval they entail between the action received by the environment and subject's reaction. Indeed, more individuality is implied, longer the time needed to process data received from the environment. Time is here intended not as an extensive but as an intensive dimension. This means that it cannot be considered as a sum of instants, but an unitary event having a specific character. This is the concept of duration in Bergson, as opposed to spatialized time, and it also recalls Bakhtin's idea of chronotope. In the overall framework interweaving design activity and time through cognition, chronotopes can be useful in the definition of an affordance-based architectural approach. Indeed some chronotopes describing duration in its becoming are related to the contingent and direct relationship between the subject and his object which is expressed by the concept of affordance. The present paper aims at understanding how these contributions from cognitive sciences, literature, philosophy and semiotics can allow architects to improve affordance as a design tool starting from a review of the state of the art. At the end, some case studies from the past which address the question of a self-determined occupancy are proposed as exemplary of an affordance-based approach to architecture

    Designing representations, affecting reality: a meta-model proposal to address the question of design epistemology from the perspective of cognitive science

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    The paper concerns representation intended as abstraction of a model from reality through perception. The relation between reality and its model is a key issue to design because while the project is thought on models, it always affects reality, and this epistemological gap is the reason for many design failures. In particular, models are adopted in top-down approaches to abstract only what decision-makers consider useful information to pursue their objectives. The bottom-up approach, instead, adopts as model reality itself intended as the total set of physical stimuli passed intact to agents which react by spontaneously transforming their environment. This approach lacking representation proves itself automatically reflexive and contingent. Nevertheless representations which make top-down approach strategic make it also rigid and vulnerable to changing conditions. The present paper outlines a research path to solve this contradiction by positing that the two approaches are not mutually exclusive but the extremes of a scale which can work as meta-model to regulate the relationship between reality and model in design activity, thus defining an intermediate design object which would determine neither a passive nor an active role of the subject with regard to his environment, but a reciprocal encounter at the phenomenal level
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