De cornelio labeone.

Thesis (doctoral)--

Vindicacion, el Coronel Carlos D. Sarmiento y el Dr. Lucio V. Lopez, ex-interventor de Buenos Aires : antecedentes, publicaciones y fallos de los tribunales federales de la provincia de Buenos Aires.

At head of title: A mis companeros del ejercito.

Reimagining the Baroque in Italian Modernism. From the fin-de-siècle to Lucio Fontana

While Italian art of the twentieth century is usually associated with either the avant-garde practices of Futurism or the classicism of Fascist visual culture, the Italian modernists' complex engagement with concepts of the ‘Baroque’ has yet to be explored. Through an extensive analysis of paintings, sculptures, publications, collecting practices, and exhibitions, my dissertation addresses this lacuna by investigating how the Baroque was discursively constructed and visually represented in Italian modernist artistic and cultural debates between 1880 and 1945. I study how artists and critics such as Umberto Boccioni, Giorgio De Chirico, Adolfo Wildt, Lucio Fontana, and Roberto Longhi championed or disparaged the Baroque in the context of heated debates over the import of Italy’s rich cultural heritage, its status in modern Europe, and the potential role of avant-garde art as a catalyst for national regeneration. In contrast to previous scholars I argue that the development of modern art in Italy was actively shaped by cultural perceptions about the Baroque. My dissertation therefore sheds new light on the role of style in the cultural politics of Italy, which in turn will transform our understanding of visual culture in modern Italy, and of twentieth-century representations of the Baroque in art, literature, and aesthetics.

Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells

Patients with metastatic melanoma or multiple myeloma have a dismal prognosis because these aggressive malignancies resist conventional treatment. A promising new oncologic approach uses molecularly targeted therapeutics that overcomes apoptotic resistance and, at the same time, achieves tumor selectivity. The unexpected selectivity of proteasome inhibition for inducing apoptosis in cancer cells, but not in normal cells, prompted us to define the mechanism of action for this class of drugs, including Food and Drug Administration-approved bortezomib. In this report, five melanoma cell lines and a myeloma cell line are treated with three different proteasome inhibitors (MG-132, lactacystin, and bortezomib), and the mechanism underlying the apoptotic pathway is defined. Following exposure to proteasome inhibitors, effective killing of human melanoma and myeloma cells, but not of normal proliferating melanocytes, was shown to involve p53-independent induction of the BH3-only protein NOXA. Induction of NOXA at the protein level was preceded by enhanced transcription of NOXA mRNA. Engagement of mitochondrial-based apoptotic pathway involved release of cytochrome c, second mitochondria-derived activator of caspases, and apoptosis-inducing factor, accompanied by a proteolytic cascade with processing of caspases 9, 3, and 8 and poly(ADP)-ribose polymerase. Blocking NOXA induction using an antisense (but not control) oligonucleotide reduced the apoptotic response by 30% to 50%, indicating a NOXA-dependent component in the overall killing of melanoma cells. These results provide a novel mechanism for overcoming the apoptotic resistance of tumor cells, and validate agents triggering NOXA induction as potential selective cancer therapeutics for life-threatening malignancies such as melanoma and multiple myeloma.

p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas

Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors.

Notch and NOXA-related pathways in melanoma cells

Notch receptor-mediated intracellular events represent an ancient cell signaling system, and alterations in Notch expression are associated with various malignancies in which Notch may function as an oncogene or less commonly as a tumor suppressor. Notch signaling regulates cell fate decisions in the epidermis, including influencing stem cell dynamics and growth/differentiation control of cells in skin. Because of increasing evidence that the Notch signaling network is deregulated in human malignancies, Notch receptors have become attractive targets for selective killing of malignant cells. Compared with proliferating normal human melanocytes, melanoma cell lines are characterized by markedly enhanced levels of activated Notch-1 receptor. By using a small molecule gamma-secretase inhibitor (GSI) consisting of a tripeptide aldehyde, N-benzyloxycarbonyl-Leu-Leu-Nle-CHO, which can block processing and activation of all four different Notch receptors, we identified a specific apoptotic vulnerability in melanoma cells. GSI triggers apoptosis in melanoma cells, but only G2/M growth arrest in melanocytes without subsequent cell death. Moreover, GSI treatment induced a pro-apoptotic BH3-only protein, NOXA, in melanoma cells but not in normal melanocytes. The use of GSI to induce NOXA induction overcomes the apoptotic resistance of melanoma cells, which commonly express numerous cell survival proteins such as Mcl-1, Bcl-2, and survivin. Taken together, these results highlight the concept of synthetic lethality in which exposure to GSI, in combination with melanoma cells overexpressing activated Notch receptors, has lethal consequences, producing selective killing of melanoma cells, while sparing normal melanocytes. By identifying signaling pathways that contribute to the transformation of melanoma cells (e.g. Notch signaling), and anti-cancer agents that achieve tumor selectivity (e.g., GSI-induced NOXA), this experimental approach provides a useful framework for future therapeutic strategies in cutaneous oncology.

An investigation into painting's transformation and regeneration through post-photographic intervention in the digital archive

This PhD practice-led research inquiry sets out to examine and describe how the fluid interactions between memory and time can be rendered via the remediation of my painting and the construction of a digital image archive. My abstract digital art and handcrafted practice is informed by Deleuze and Guattari’s rhizomics of becoming. I aim to show that the technological mobility of my creative strategies produce new conditions of artistic possibility through the mobile principles of rhizomic interconnection, multiplicity and diversity. Subsequently through the ongoing modification of past painting I map how emergent forms and ideas open up new and incisive engagements with the experience of a ‘continual present’. The deployment of new media and cross media processes in my art also deterritorialises the modernist notion of painting as a static and two dimensional spatial object. Instead, it shows painting in a postmodern field of dynamic and transformative intermediality through digital formats of still and moving images that re-imagines the relationship between memory, time and creative practice.

Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated in-bred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK ) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.

The primary school as a logic machine

This paper makes a case for thinking about the primary school as a logic machine (apparatus) as a way of thinking about processes of in-school stratification. Firstly we discuss related literature on in-school stratification in primary schools, particularly as it relates to literacy learning. Secondly we explain how school reform can be thought about in terms of the idea of the machine or apparatus. In which case the processes of in-school stratification can be mapped as more than simply concerns about school organisation (such as students grouping) but also involve a politics of truth, played out in each school, that constitutes school culture and what counts as ‘good’ pedagogy. Thirdly, the chapter will focus specifically on research conducted into primary schools in the Northern Suburbs of Adelaide, one of the most educationally disadvantaged regions in Australia, as a case study of the relationship between in-school stratification and the reproduction of inequality. We will draw from more than 20 years of ethnographic work in primary school in the northern suburbs of Adelaide and provide a snapshot of a recent attempt to improve literacy achievement in a few Northern Suburbs public primary schools (SILA project). The SILA project, through diagnostic reviews, has provided a significant analysis of the challenges facing policy and practice in such challenging school contexts that also maps onto existing (inter)national research. These diagnostic reviews said ‘hard things’ that required attention by SILA schools and these included: · an over reliance on whole class, low level, routine tasks and hence a lack of challenge and rigour in the learning tasks offered to students ; · a focus on the 'code breaking' function of language at the expense of richer conceptualisations of literacy that might guide teachers’ understanding of challenging pedagogies ; · the need for substantial shifts in the culture of schools, especially unsettling deficit views of students and their communities ; · a need to provide a more ‘consistent’ approach to teaching literacy across the school; · a need to focus School Improvement Plans in order to implement a clear focus on literacy learning; and, · a need to sustain professional learning to produce new knowledge and practice . The paper will conclude with suggestions for further research and possible reform projects into the primary school as a logic machine.

Sapientia, 1950, Vol. V, nº 15 (número completo)

Contenido: Existencialismo y política / La Dirección – La crítica de Kierkegaard al ochocientos / Cornelio Fabro – El problema de la verdad en Heidegger / Ramón Ceñal – El existencialismo de Gabriel Marcel / Octavio Nicolás Derisi – Notas y comentarios -- Bibliografía

Teología, 2008, Tomo XLV nº 97 (número completo)

Nota del Director -- Breve exposición de la hermenéutica analógica / Mauricio Beuchot -- ¿Fin de la antropología alma-cuerpo? / Lucio Florio -- Michel de Certeau : recorridos por el "creer" y sus constelaciones contemporáneas / Marcelo González -- Justicia, caridad y solidaridad en la DSI / Gustavo Irrazábal -- "Las palabras del Grito" / Hugo Rodolfo Safa -- Grupo de estudio bíblico judío cristiano / Víctor M. Fernández -- Una aproximación al acompañamiento espiritual en San Juan de la Cruz -- El lenguaje de la vida en la estética hildegardiana / Cecilia Inés Avenatti de Palumbo -- Reflexiones sobre la experiencia religiosa durante la crisis de identidad de la adolescencia / Julio V. Maffei -- Catalina de Siena : su teología hecha biografía / Gabriela María Di Renzo -- Espiritualidad sanante : salud y espiritualidad en Anselm Grün / Mónica Cristina Ukaski -- El legado póstumo de José Carlos Barcellos / Alberto Toutin -- Notas bibliográficas

Sapientia, 1952, Vol. VII, nº 26 (número completo)

Contenido: ¿Europeos o americanos? / La Dirección – Kierkegaard y Marx / Cornelio Fabro – Panorama filosófico en el Méjico actual / José Rubén Sanabria – Notas y comentarios -- Bibliografía