Marcel Breuer y el sueño de la cabaña americana

Marcel Breuer arquitecto húngaro y afamado diseñador de mobiliario procedente de la Bauhaus, emigra a Estados Unidos en 1937, invitado por Gropius como profesor en Harvard. Allí comienzan, Breuer y Gropius, una nueva etapa basada en la experimentación de la casa como revisión de los postulados de la arquitectura moderna: la casa como máquina de habitar, propuesta por Le Corbusier, procedente de la vieja Europa; versus la humanización de la máquina a través del efecto del material sobre la estructura y la forma extendidas y en contacto con el territorio, propuesta por Frank Lloyd Wright procedente de la nueva América. Sus experimentos domésticos sobre la casa-cabaña acercaron los métodos tradicionales de la construcción americana a una visión renovada abstracta y pura, donde los modos de vida, los requerimientos básicos, prácticos y funcionales se transformaron en la conexión del "Arte de Construir" a través del material y su puesta en obra. La búsqueda de una respuesta clara del habitar que satisfacía objetivos opuestos y necesidades humanas, llevó a su arquitectura de la abstracción a reconciliar al hombre con la naturaleza, dotarla de arte y vida, arquitectura y paisaje que pasaron a convertirse en los ideales modernos de la cabaña americana. ABSTRACT. Marcel Breuer, Hungarian architect and famed to furniture's designer of the Bauhaus emigrated to America in 1937, invited by Gropius as a professor at Harvard. Breuer and Gropius, there begin a new stage based on the experimentation of the house as a revision to the postulates of modern architecture: the house as a dwell machine proposed by Le Corbusier from old Europe; versus the humanization of the machine through the effect of material on the structure and form extended and in contact with the territory, proposed by Frank LI. Wright from the new America. His experiments on the house-cottage approached traditional methods of the American construction methods to a new vision, abstract and pure, where ways of life, and basic, practical and functional requirements became the connection to "Art of Building" trough the material and its placing. The search for a clear answer of dwelling that satisfied conflicting objectives and human needs, led to the architecture of abstraction to reconcile man with nature, endow it with life and art, an architecture and a landscape that became the modern ideals of American cottage

3D high definition video coding on a GPU-based heterogeneous system

H.264/MVC is a standard for supporting the sensation of 3D, based on coding from 2 (stereo) to N views. H.264/MVC adopts many coding options inherited from single view H.264/AVC, and thus its complexity is even higher, mainly because the number of processing views is higher. In this manuscript, we aim at an efficient parallelization of the most computationally intensive video encoding module for stereo sequences. In particular, inter prediction and its collaborative execution on a heterogeneous platform. The proposal is based on an efficient dynamic load balancing algorithm and on breaking encoding dependencies. Experimental results demonstrate the proposed algorithm's ability to reduce the encoding time for different stereo high definition sequences. Speed-up values of up to 90× were obtained when compared with the reference encoder on the same platform. Moreover, the proposed algorithm also provides a more energy-efficient approach and hence requires less energy than the sequential reference algorith

Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis

Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence

The Air Microwave Yield (AMY) experiment - A laboratory measurement of the microwave emission from extensive air showers

The AMY experiment aims to measure the microwave bremsstrahlung radiation (MBR) emitted by air-showers secondary electrons accelerating in collisions with neutral molecules of the atmosphere. The measurements are performed using a beam of 510 MeV electrons at the Beam Test Facility (BTF) of Frascati INFN National Laboratories. The goal of the AMY experiment is to measure in laboratory conditions the yield and the spectrum of the GHz emission in the frequency range between 1 and 20 GHz. The final purpose is to characterise the process to be used in a next generation detectors of ultra-high energy cosmic rays. A description of the experimental setup and the first results are presented.Comment: 3 pages -- EPS-HEP'13 European Physical Society Conference on High Energy Physics (July, 18-24, 2013) at Stockholm, Swede

CD44 Modulates Cell Migration and Invasion in Ewing Sarcoma Cells

The chimeric EWSR1::FLI1 transcription factor is the main oncogenic event in Ewing sarcoma. Recently, it has been proposed that EWSR1::FLI1 levels can fluctuate in Ewing sarcoma cells, giving rise to two cell populations. EWSR1::FLI1low cells present a migratory and invasive phenotype, while EWSR1::FLI1high cells are more proliferative. In this work, we described how the CD44 standard isoform (CD44s), a transmembrane protein involved in cell adhesion and migration, is overexpressed in the EWSR1::FLI1low phenotype. The functional characterization of CD44s (proliferation, clonogenicity, migration, and invasion ability) was performed in three doxycycline-inducible Ewing sarcoma cell models (A673, MHH-ES1, and CADO-ES1). As a result, CD44s expression reduced cell proliferation in all the cell lines tested without affecting clonogenicity. Additionally, CD44s increased cell migration in A673 and MHH-ES1, without effects in CADO-ES1. As hyaluronan is the main ligand of CD44s, its effect on migration ability was also assessed, showing that high molecular weight hyaluronic acid (HMW-HA) blocked cell migration while low molecular weight hyaluronic acid (LMW-HA) increased it. Invasion ability was correlated with CD44 expression in A673 and MHH-ES1 cell lines. CD44s, upregulated upon EWSR1::FLI1 knockdown, regulates cell migration and invasion in Ewing sarcoma cells.This project was funded by Instituto de Salud Carlos III, grant numbers PI20CIII/00020, DTS18CIII/00005, Asociación Pablo Ugarte, grant numbers TRPV205/18; Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, grant numbers TVP333-19, TVP-1324/15; ASION, grant number TVP141/17. Enrique Fernández-Tabanera is supported by Asociación Candela Riera, Asociación Todos Somos Iván & Fundación Sonrisa de Alex, Saint T. Cervera is supported by Asociación Pablo Ugarte and Raquel M. Melero is supported by a CIBERER contract.S

Circulating adrenomedullin in cirrhosis: relationship to hyperdynamic circulation

BACKGROUND/AIMS: Peripheral arterial vasodilation may be the key factor in the sodium and water retention of cirrhosis. The mechanism responsible for this vasodilation remains to be fully elucidated. Adrenomedullin is a novel peptide, highly expressed in cardiovascular tissues, with potent and long-lasting vasodilating activity. METHODS: The possible implication of adrenomedullin in the hemodynamic changes of cirrhosis has been investigated. We measured the plasma concentration of adrenomedullin in 20 cirrhotic patients and 11 healthy subjects. In addition, systemic, portal and renal hemodynamics, hormonal factors and renal function parameters were evaluated in the same patients. RESULTS: Circulating adrenomedullin was significantly higher in the group of patients with cirrhosis (72.1; 46-100 vs 21.6; 11-34 fmol/dl, respectively; p<0.02) and was directly correlated with the Pugh score (r: 0.6; p: 0.01), inversely correlated with the creatinine clearance (r: -0.6; p<0.01) and tended to inversely correlate with systemic vascular resistance index (r: -0.46; p: 0.07). There were no portal-peripheral differences in adrenomedullin levels. Transjugular intrahepatic portosystemic shunt insertion did not induce changes in the peripheral concentration of adrenomedullin, but baseline values of this hormone predicted the degree of hyperdynamic circulation after TIPS. CONCLUSIONS: Circulating adrenomedullin is increased in cirrhosis. These levels increase with the severity of the disease, especially in patients with hepatorenal syndrome. This peptide may contribute to vasodilation of cirrhosis

Dual ifgMosaic: A Versatile Method for Multispectral and Combinatorial Mosaic Gene-Function Analysis

Improved methods for manipulating and analyzing gene function have provided a better understanding of how genes work during organ development and disease. Inducible functional genetic mosaics can be extraordinarily useful in the study of biological systems; however, this experimental approach is still rarely used in vertebrates. This is mainly due to technical difficulties in the assembly of large DNA constructs carrying multiple genes and regulatory elements and their targeting to the genome. In addition, mosaic phenotypic analysis, unlike classical single gene-function analysis, requires clear labeling and detection of multiple cell clones in the same tissue. Here, we describe several methods for the rapid generation of transgenic or gene-targeted mice and embryonic stem (ES) cell lines containing all the necessary elements for inducible, fluorescent, and functional genetic mosaic (ifgMosaic) analysis. This technology enables the interrogation of multiple and combinatorial gene function with high temporal and cellular resolution.This work was supported by grants to the PI R.B. from the Spanish Ministry of Economy, Industry and Competitiveness (SAF2013-44329-P, SAF2013-42359-ERC, and RYC-2013-13209) and European Research Council (ERC-2014-StG - 638028). S.P.-Q., M.F.-C., and I.G.-G. were supported by PhD fellowships from Fundacion La Caixa (CX-SO-2013-02, CX\_E-2015-01, and CX-SO-16-1, respectively). W.L. by a FP7-PEOPLE-2012-COFUND GA600396 postdoctoral contract. We thank Simon Bartlett for English editing, Ralf H. Adams for sharing the Cdh5(PAC)-CreERT2 mice, Jose Luis de La Pompa for comments throughout the project and for sharing the Tie2-Cre mice, Gonzalo Gancedo for the help with the mouse colony, Valeria Caiolfa for the help with the microscopy, and all the members of the CNIC gene targeting, transgenesis, cellomics, and microscopy units. The CNIC is supported by MEIC/MINECO and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: a new role for homocysteine in liver fibrosis

Elevated plasma levels of homocysteine have been shown to interfere with normal cell function in a variety of tissues and organs, such as the vascular wall and the liver. However, the molecular mechanisms behind homocysteine effects are not completely understood. In order to better characterize the cellular effects of homocysteine, we have searched for changes in gene expression induced by this amino acid. Our results show that homocysteine is able to induce the expression and synthesis of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in a variety of cell types ranging from vascular smooth muscle cells to hepatocytes, HepG2 cells and hepatic stellate cells. In this latter cell type, homocysteine also stimulated alpha 1(I) procollagen mRNA expression. TIMP-1 induction by homocysteine appears to be mediated by its thiol group. Additionally, we demonstrate that homocysteine is able to promote activating protein-1 (AP-1) binding activity, which has been shown to be critical for TIMP-1 induction. Our findings suggest that homocysteine may alter extracellular matrix homeostasis on diverse tissular backgrounds besides the vascular wall. The liver could be considered as another target for such action of homocysteine. Consequently, the elevated plasma levels of this amino acid found in different pathological or nutritional circumstances may cooperate with other agents, such as ethanol, in the onset of liver fibrosis

Endoscopical and pathological dissociation in severe colitis induced by immune-checkpoint inhibitors

Checkpoint inhibitors have improved the survival of patients with advanced tumors and show a manageable toxicity profile. However, auto-immune colitis remains a relevant side effect, and combinations of anti-PD1/PDL1 and anti-CTLA-4 increase its incidence and severity. Here, we report the case of a 50-year-old patient diagnosed with stage IV cervical cancer that relapsed following radical surgery, external radiation/brachytherapy and standard chemotherapy. She was subsequently treated with Nivolumab and Ipilimumab combination and developed grade 2 colitis presenting a dissociation between endoscopic and pathological findings. At cycle 10 the patient reported grade 3 diarrhea and abdominal discomfort, without blood or mucus in the stools. Immunotherapy was withheld and a colonoscopy was performed, showing normal mucosa in the entire colon. Puzzlingly, histologic evaluation of randomly sampled mucosal biopsy of the distal colon showed an intense intraepithelial lymphocyte infiltration with crypt loss and some regenerating crypts with a few apoptotic bodies set in a chronically inflamed lamina propria, consistent with the microscopic diagnosis of colitis. Treatment with methylprednisolone 2 mg/kg was initiated which led to a decrease in the number of stools to grade 1. Additional investigations to exclude other causes of diarrhea rendered negative results. The patient experienced a major partial response and, following the resolution of diarrhea, she was re-challenged again with immunotherapy, with the reappearance of grade 2 diarrhea, leading to permanent immunotherapy interruption. We conclude and propose that performing random colonic biopsies should be considered in cases of immune checkpoint-associated unexplained diarrhea, even when colonoscopy shows macroscopically normal colonic mucosa inflammatory lesions