To fasten words again to visible – and invisible – things

In this extended introductory essay, Catherine Gander and Sarah Garland suggest new ways of looking at the correspondences between visual and verbal practices to consider their material and conceptual connections in a specifically American set of histories, contexts and interpretive traditions. Tracing a lineage of experiential philosophy that is grounded in the overturning of a Cartesian mind/body split, the authors argue for pluralistic perspectives on intermedial innovations that situate embodied and imaginative reader-viewer response as vital to the life of the artwork. Gander and Garland chart two main strands to this approach: the pragmatist strain of American aesthetics and social politics, rooted in the essays of transcendentalist Ralph Waldo Emerson and emanating from the writings of John Dewey and William James; and the conceptualist strain of French-American Marcel Duchamp, whose ground-breaking ideas both positioned the artwork as a phenomenological construction and liberated the artist from established methods of practice and discourse. The ‘imagetext’ (after W. J. T. Mitchell) is therefore, argue Gander and Garland, a site consisting of far more than word and image – but a living assemblage of language, idea, thing, cognition, affect and shared experience.

EARLY RADIO AND X-RAY OBSERVATIONS OF THE YOUNGEST NEARBY TYPE Ia SUPERNOVA PTF 11kly (SN 2011fe)

On 2011 August 24 (UT) the Palomar Transient Factory (PTF) discovered PTF11kly (SN 2011fe), the youngest and most nearby Type Ia supernova (SN Ia) in decades. We followed this event up in the radio (centimeter and millimeter bands) and X-ray bands, starting about a day after the estimated explosion time. We present our analysis of the radio and X-ray observations, yielding the tightest constraints yet placed on the pre-explosion mass-loss rate from the progenitor system of this supernova. We find a robust limit of from sensitive X-ray non-detections, as well as a similar limit from radio data, which depends, however, on assumptions about microphysical parameters. We discuss our results in the context of single-degenerate models for SNe Ia and find that our observations modestly disfavor symbiotic progenitor models involving a red giant donor, but cannot constrain systems accreting from main-sequence or sub-giant stars, including the popular supersoft channel. In view of the proximity of PTF11kly and the sensitivity of our prompt observations, we would have to wait for a long time (a decade or longer) in order to more meaningfully probe the circumstellar matter of SNe Ia.

GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

BACKGROUND: In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease.

METHODS: We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively.

RESULTS: Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples.

CONCLUSIONS: These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.

METHODS: We conducted a phase 2 trial in which patients with metastatic, castration-resistant prostate cancer were treated with olaparib tablets at a dose of 400 mg twice a day. The primary end point was the response rate, defined either as an objective response according to Response Evaluation Criteria in Solid Tumors, version 1.1, or as a reduction of at least 50% in the prostate-specific antigen level or a confirmed reduction in the circulating tumor-cell count from 5 or more cells per 7.5 ml of blood to less than 5 cells per 7.5 ml. Targeted next-generation sequencing, exome and transcriptome analysis, and digital polymerase-chain-reaction testing were performed on samples from mandated tumor biopsies.

RESULTS: Overall, 50 patients were enrolled; all had received prior treatment with docetaxel, 49 (98%) had received abiraterone or enzalutamide, and 29 (58%) had received cabazitaxel. Sixteen of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%). Of these 16 patients, 14 (88%) had a response to olaparib, including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib.

CONCLUSIONS: Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNA-repair genes led to a high response rate. (Funded by Cancer Research UK and others; ClinicalTrials.gov number, NCT01682772; Cancer Research UK number, CRUK/11/029.).

Julius Caesar, August 8, 1939

Concert program for Julius Caesar, August 8, 1939

Marriage of Figaro, January 22, 1940

Concert program for Marriage of Figaro, January 22, 1940

Medicinal chemistry approaches to malaria drug discovery

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2016

Identification of image attributes that are most affected with changes in displayed image size

This paper describes an investigation of changes in image appearance when images are viewed at different image sizes on a high-end LCD device. Two digital image capturing devices of different overall image quality were used for recording identical natural scenes with a variety of pictorial contents. From each capturing device, a total of sixty four captured scenes, including architecture, nature, portraits, still and moving objects and artworks under various illumination conditions and recorded noise level were selected. The test set included some images where camera shake was purposefully introduced. An achromatic version of the image set that contained only lightness information was obtained by processing the captured images in CIELAB space. Rank order experiments were carried out to determine which image attribute(s) were most affected when the displayed image size was altered. These evaluations were carried out for both chromatic and achromatic versions of the stimuli. For the achromatic stimuli, attributes such as contrast, brightness, sharpness and noisiness were rank-ordered by the observers in terms of the degree of change. The same attributes, as well as hue and colourfulness, were investigated for the chromatic versions of the stimuli. Results showed that sharpness and contrast were the two most affected attributes with changes in displayed image size. The ranking of the remaining attributes varied with image content and illumination conditions. Further, experiments were carried out to link original scene content to the attributes that changed mostly with changes in image size.

Die Fledermaus, November 18, 19, 21, and 22, 1977

Concert program for Die Fledermaus, November 18, 19, 21, and 22, 1977

The Consul March 2 & 5, 1966

Concert program for The Consul March 2 & 5, 1966

An Evening of Opera Excerpts, December 4, 1965

Concert program for An Evening of Opera Excerpts, December 4, 1965

An Open Source BI Approach: Concept Proof Tracking Fleet

É possível assistir nos dias de hoje, a um processo tecnológico evolutivo acentuado por toda a parte do globo. No caso das empresas, quer as pequenas, médias ou de grandes dimensões, estão cada vez mais dependentes dos sistemas informatizados para realizar os seus processos de negócio, e consequentemente à geração de informação referente aos negócios e onde, muitas das vezes, os dados não têm qualquer relacionamento entre si. A maioria dos sistemas convencionais informáticos não são projetados para gerir e armazenar informações estratégicas, impossibilitando assim que esta sirva de apoio como recurso estratégico. Portanto, as decisões são tomadas com base na experiência dos administradores, quando poderiam serem baseadas em factos históricos armazenados pelos diversos sistemas. Genericamente, as organizações possuem muitos dados, mas na maioria dos casos extraem pouca informação, o que é um problema em termos de mercados competitivos. Como as organizações procuram evoluir e superar a concorrência nas tomadas de decisão, surge neste contexto o termo Business Intelligence(BI). A GisGeo Information Systems é uma empresa que desenvolve software baseado em SIG (sistemas de informação geográfica) recorrendo a uma filosofia de ferramentas open-source. O seu principal produto baseia-se na localização geográfica dos vários tipos de viaturas, na recolha de dados, e consequentemente a sua análise (quilómetros percorridos, duração de uma viagem entre dois pontos definidos, consumo de combustível, etc.). Neste âmbito surge o tema deste projeto que tem objetivo de dar uma perspetiva diferente aos dados existentes, cruzando os conceitos BI com o sistema implementado na empresa de acordo com a sua filosofia. Neste projeto são abordados alguns dos conceitos mais importantes adjacentes a BI como, por exemplo, modelo dimensional, data Warehouse, o processo ETL e OLAP, seguindo a metodologia de Ralph Kimball. São também estudadas algumas das principais ferramentas open-source existentes no mercado, assim como quais as suas vantagens/desvantagens relativamente entre elas. Em conclusão, é então apresentada a solução desenvolvida de acordo com os critérios enumerados pela empresa como prova de conceito da aplicabilidade da área Business Intelligence ao ramo de Sistemas de informação Geográfica (SIG), recorrendo a uma ferramenta open-source que suporte visualização dos dados através de dashboards.

Recueil de pièces sur l'Inde française.

Contient : « Nottes critiques sur l'Histoire des Indes anciennes et modernes de M. l'abbé Guyon, par M. Pilavoine » ; « Remarques touchant l'établissement de l'ancienne Compagnie de France pour le commerce des Indes orientales » ; «Lettre de M. le chevalier Hébert, gouverneur du Fort-Louis et de la ville de Pondichery, aux plaintes du R. P. Tachard, supérieur des Jésuites de la même ville, 1708 » ; « Guerres du Mogol entre le roi de Perse Nader Scha ou Thomas Couli-Kan, en 1735 et 1736 » ; « Précis historique de l'origine de la guerre entreprise par M. Dupleix, en 1749, contre les Maures, ainsy que des donations qui ont été faites à la Compagnie successivement jusqu'en 1753 » ; « Relation du siège de Pondichery, levé par les Anglois le 18 oct. 1748 » ; « Relation de la victoire remportée sur Nazerzingue par l'armée françoise, commandée par M. de La Touche, le 16 déc. 1750 » ; « Relation des principaux évènemens arrivés aux Indes dans la province de Carnate et le long de la côte Coromandel entre les François et les Anglois » (1749-1752) ; « Traduction des lettres de Saadoulakan Bahadour Mouzaferjingu, soubedar de la province de Dakan [et de quelques autres lettres] à Mr Bupleix, gouverneur de Pondichery » ; « Relation du siège de Pondicheri par les Anglois en 1748 » ; « Tableau général des troupes formant la garnison de Pondichery... 1755, » etc