123 research outputs found

    The Critical Approach of ‘Plug’ in Re-Conceptualisation of Architectural Program

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    [EN] This paper explores the issue of ‘plug’ in designing program within particular experimental studies in architecture. There was what could be called a critical ‘elaboration’ of program in Archigram’s 1964 ‘Plug-In’ City project, while intriguingly the critical approach taken in the 2001 ‘Un-Plug’ project of Francois Roche and Stephanie Lavaux hinted at a ‘re-evaluation’ of ‘plug’ related to program in architecture. The embedded criticism and creative programmatic suggestions in both projects will be discussed from the point of view of using the accumulated urbanscape as a potential for contemplation, a theme that has also been elaborated, both theoretically and experimentally, by the artist/architect Gordon Matta-Clark in his 1978 ‘Balloon Housing’ project. These experimentations - about the ‘plug’ - need to be discussed in order to understand their contributions as traceable sources to program issue in contemporary architecture.[ES] Este artículo sugiere una lectura incisiva del concepto de “plug” en el diseño de los programas arquitectónicos, mediante la exploración de conexiones/temas entre espacios arquitectónicos de determinados estudios experimentales. Hubo un ‘elaboración’ crítica del programa en el proyecto ‘Plug-In’ City de Archigram de 1964, y curiosamente el enfoque adoptado en el proyecto ‘Un-Plug” de Francois Roche y Stephanie Lavaux de 2001 hizo alusión a una “re-evaluación’ del ‘plug’ en relación a los programas de arquitectura. La crítica inmanente y las creativas sugerencias programáticas en ambos proyectos se analizarán desde el punto de vista de la utilización del paisaje urbano acumulado como potencial para la contemplación, un tema que también ha sido abordado, tanto teórica como experimentalmente, por el artista/arquitecto Gordon Matta-Clark en su proyecto ‘Balloon Housing’ 1978. Estas experimentaciones –sobre el concepto de “plug”– necesitan ser estudiadas con el fin de comprender sus aportaciones como fuentes rastreables en las cuestiones programáticas de la arquitectura contemporánea.Beslioglu, B. (2014). Aproximación crítica del "plug" en la re-conceptualización del programa arquitectónico. VLC arquitectura. Research Journal. 1(1):59-76. doi:http://dx.doi.org/10.4995/vlc.2014.1829.SWORD597611Anderson, S. The Fiction of Function. Assemblage, 2, February 1987COOK, Peter, Warren Chalk, Dennis Crompton, David Greene, Ron Herron, Mike Webb. Archigram. New York: Princeton Architectural Press, 1999COOK Peter. Experimental Architecture. London: Academy Editions, 1972Deamer, P. The Everyday and The Utopian. In: S. Harris and D. Berkeed, ed., Architecture of the Everyday. New York: Princeton Publications, 1997Fend, P. New Architecture from Matta-Clark. In: S. Breitweiser. ed., Reorganizing Structure by Drawing Through It. Vienna: Generali Foundation, 199

    Dual-Query Multiple Instance Learning for Dynamic Meta-Embedding based Tumor Classification

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    Whole slide image (WSI) assessment is a challenging and crucial step in cancer diagnosis and treatment planning. WSIs require high magnifications to facilitate sub-cellular analysis. Precise annotations for patch- or even pixel-level classifications in the context of gigapixel WSIs are tedious to acquire and require domain experts. Coarse-grained labels, on the other hand, are easily accessible, which makes WSI classification an ideal use case for multiple instance learning (MIL). In our work, we propose a novel embedding-based Dual-Query MIL pipeline (DQ-MIL). We contribute to both the embedding and aggregation steps. Since all-purpose visual feature representations are not yet available, embedding models are currently limited in terms of generalizability. With our work, we explore the potential of dynamic meta-embedding based on cutting-edge self-supervised pre-trained models in the context of MIL. Moreover, we propose a new MIL architecture capable of combining MIL-attention with correlated self-attention. The Dual-Query Perceiver design of our approach allows us to leverage the concept of self-distillation and to combine the advantages of a small model in the context of a low data regime with the rich feature representation of a larger model. We demonstrate the superior performance of our approach on three histopathological datasets, where we show improvement of up to 10% over state-of-the-art approaches

    Allogeneic Hematopoietic Stem Cell Transplantation in a Rare Case of Tonsillar Mast Cell Sarcoma

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    Mast cell sarcoma comprises a rare aggressive mast cell neoplasia with histological, clinical, and genetic features distinct from other mast cell neoplasm. Until now, prognosis is still poor due to high rates of progression to mast cell leukemia and failure of conventional chemotherapies. Our here presented first report about successful allogeneic hematopoietic stem cell transplantation leading to remission in a case of tonsillar MCS represents a promising potential curative treatment option for this rare and often fatal disease. Key-Points: - Mast cell sarcoma (MCS) is a rare, aggressive mast cell neoplasia with a very poor prognosis and a median survival of <18 months. - Allo-HSCT represents a promising potential curative treatment option for this rare and often fatal disease

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    The molecular hallmarks of primary and secondary vitreoretinal lymphoma

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    Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Because of its rarity and the difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The purpose of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next-generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples from 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNAs) were assessed using the OncoScan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%), and 9p21/CDKN2A deletions (75%) were the most common alterations, with similar frequencies in primary (n = 16), synchronous (n = 3), or secondary (n = 12) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. OncoScan analysis demonstrated a high number of CNAs (mean 18.6 per case). Negative controls lacked mutations or CNAs. Using cell-free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all cases examined. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell-free DNA derived from the vitreous

    STAT3 regulated ARF expression suppresses prostate cancer metastasis.

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    Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14(ARF) expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.Lukas Kenner and Jan Pencik are supported by FWF, P26011 and the Genome Research-Austria project “Inflammobiota” grants. Helmut Dolznig is supported by the Herzfelder Family Foundation and the Niederösterr. Forschungs-und Bildungsges.m.b.H (nfb). Richard Moriggl is supported by grant SFB-F2807 and SFB-F4707 from the Austrian Science Fund (FWF), Ali Moazzami is supported by Infrastructure for biosciences-Strategic fund, SciLifeLab and Formas, Zoran Culig is supported by FWF, P24428, Athena Chalaris and Stefan Rose-John are supported by the Deutsche Forschungsgemeinschaft (Grant SFB 877, Project A1and the Cluster of Excellence --“Inflammation at Interfaces”). Work of the Aberger lab was supported by the Austrian Science Fund FWF (Projects P25629 and W1213), the European FP7 Marie-Curie Initial Training Network HEALING and the priority program Biosciences and Health of the Paris-Lodron University of Salzburg. Valeria Poli is supported by the Italian Association for Cancer Research (AIRC, No IG13009). Richard Kennedy and Steven Walker are supported by the McClay Foundation and the Movember Centre of Excellence (PC-UK and Movember). Gerda Egger is supported by FWF, P27616. Tim Malcolm and Suzanne Turner are supported by Leukaemia and Lymphoma Research.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms873

    Molecular and functional profiling identifies therapeutically targetable vulnerabilities in plasmablastic lymphoma

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    Plasmablastic lymphoma (PBL) represents a rare and aggressive lymphoma subtype frequently associated with immunosuppression. Clinically, patients with PBL are characterized by poor outcome. The current understanding of the molecular pathogenesis is limited. A hallmark of PBL represents its plasmacytic differentiation with loss of B-cell markers and, in 60% of cases, its association with Epstein-Barr virus (EBV). Roughly 50% of PBLs harbor a MYC translocation. Here, we provide a comprehensive integrated genomic analysis using whole exome sequencing (WES) and genome-wide copy number determination in a large cohort of 96 primary PBL samples. We identify alterations activating the RAS-RAF, JAK-STAT, and NOTCH pathways as well as frequent high-level amplifications in MCL1 and IRF4. The functional impact of these alterations is assessed using an unbiased shRNA screen in a PBL model. These analyses identify the IRF4 and JAK-STAT pathways as promising molecular targets to improve outcome of PBL patients
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