Structural Performance of Reinforced Concrete Flat Plate Buildings Subjected to Fire

El siguiente artículo se propone estudiar la poesía de Luis Hernández a partir de los problemas que surgen al intentar estudiar su obra reunida. Antes que ser valorada como una poesía “inacabada”, la deliberada asistematicidad de su poética debe ser entendida como el resultado de un calculado y consciente ejercicio artístico, cuyas fuentes filosóficas tradicionalmente han pugnado por una ontología del movimiento frente a una metafísica de la permanencia. Bajo esta perspectiva, la obra de Hernández se revela como un “plano de inmanencia”, desde el cual acontece el sentido de su poesía en el quehacer de la escritura.The article aims to study Luis Hernández’ poetry from the point of view of the problems that emerge when trying to analyze his Complete Works. Rather than being assessed as “unfinished”, the deliberate and unsystematic appearance of his poetic, should rather be understood as the result of a calculated and conscious artistic practice that stems from philosophical trends which traditionally have fostered an ontology of movement against a metaphysics of permanence. Under this view, Hernández work shows up as “plane of immanence” from where sense becomes an event for the creative writing process.El següent article es proposa estudiar la poesia de Luis Hernández a partir dels problemes que sorgeixen al tractar d’estudiar la seva obra reunida. Abans de ser valorada com una poesia “incabada”, la deliberada asistematicitat de la seva poètica deu ser entesa com el resultat d’un calculat i conscient exercici artístic, fonts filosòfiques de les quals han pugnat tradicionalment per una ontologia del moviment davant una metafísica de la permanència. Sota aquesta perspectiva, l’obra d’Hernàndez es revela com un “pla d’inmanència”, des del qual esdevé el sentit de la seva poesia en el afer de l’escriptura

Effect of troglitazone on tumor growth and pulmonary metastasis development of the mouse osteosarcoma cell line LM8

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma often develops micrometastases in the lung prior to diagnosis, causing a fatal outcome. Therefore, the prevention of pulmonary metastases is critical for the improvement of the prognosis of patients with osteosarcoma. The purpose of this study was to investigate whether troglitazone (TGZ) is considered as possible therapeutics in the treatment of growth and metastasis of osteosarcoma.</p> <p>Methods</p> <p>LM8 cells were treated for 3 days with various concentrations of TGZ. The effect of TGZ on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine incorporation study. The assay of cell invasion and motility was performed using either the Matrigel-coated cell culture inserts or the uncoated cell culture inserts in the invasion chambers. The effect of TGZ on Akt signaling was assessed by Western blot analysis of Akt and p-Akt. The effects of oral administration of either TGZ (TGZ group) or ethanol (control group) on the growth of primary tumor and the development of pulmonary metastasis were examined in nude mice implanted with LM8 cells on their backs. The expression and activity of matrix metalloproteinase 2 (MMP-2) within the tumor were determined by immunohistochemistry and zymography. The microvessel density (MVD) within the tumor was determined by immunohistochemistry for CD34.</p> <p>Results</p> <p>TGZ dose-dependently inhibits cell proliferation. TGZ-treated cells were less invasive and less motile than untreated cells. The activity of MMP-2 secreted by TGZ-treated cells was lower than that secreted by untreated cells. TGZ decreased the level of p-Akt. The primary tumor mass was smaller in the TGZ group than in the control group. The TGZ group had less metastatic tumors in the lung compared with the control group. The expression and activity of MMP-2 within the tumor of the TGZ group were lower than those of the control group. The MVD within the tumor of the TGZ group was lower than that of the control group.</p> <p>Conclusions</p> <p>Inhibition of Akt signaling by TGZ may decrease the secretion of MMP-2, resulting in the decrease of invasiveness and motility in LM8 cells. Treatment of tumor-bearing mice with TGZ decreases the expression and activity of MMP-2 within the tumor, and inhibits primary tumor growth and pulmonary metastasis development. TGZ may offer a new approach in chemotherapy for osteosarcoma.</p

Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated.</p> <p>Methods</p> <p>In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference.</p> <p>Results</p> <p>We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's <it>t </it>test.</p> <p>Conclusions</p> <p>To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined.</p

A Catalytic Mechanism for Cysteine N-Terminal Nucleophile Hydrolases, as Revealed by Free Energy Simulations

The N-terminal nucleophile (Ntn) hydrolases are a superfamily of enzymes specialized in the hydrolytic cleavage of amide bonds. Even though several members of this family are emerging as innovative drug targets for cancer, inflammation, and pain, the processes through which they catalyze amide hydrolysis remains poorly understood. In particular, the catalytic reactions of cysteine Ntn-hydrolases have never been investigated from a mechanistic point of view. In the present study, we used free energy simulations in the quantum mechanics/molecular mechanics framework to determine the reaction mechanism of amide hydrolysis catalyzed by the prototypical cysteine Ntn-hydrolase, conjugated bile acid hydrolase (CBAH). The computational analyses, which were confirmed in water and using different CBAH mutants, revealed the existence of a chair-like transition state, which might be one of the specific features of the catalytic cycle of Ntn-hydrolases. Our results offer new insights on Ntn-mediated hydrolysis and suggest possible strategies for the creation of therapeutically useful inhibitors

Carotenoid Distribution in Living Cells of Haematococcus pluvialis (Chlorophyceae)

Haematococcus pluvialis is a freshwater unicellular green microalga belonging to the class Chlorophyceae and is of commercial interest for its ability to accumulate massive amounts of the red ketocarotenoid astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione). Using confocal Raman microscopy and multivariate analysis, we demonstrate the ability to spectrally resolve resonance–enhanced Raman signatures associated with astaxanthin and β-carotene along with chlorophyll fluorescence. By mathematically isolating these spectral signatures, in turn, it is possible to locate these species independent of each other in living cells of H. pluvialis in various stages of the life cycle. Chlorophyll emission was found only in the chloroplast whereas astaxanthin was identified within globular and punctate regions of the cytoplasmic space. Moreover, we found evidence for β-carotene to be co-located with both the chloroplast and astaxanthin in the cytosol. These observations imply that β-carotene is a precursor for astaxanthin and the synthesis of astaxanthin occurs outside the chloroplast. Our work demonstrates the broad utility of confocal Raman microscopy to resolve spectral signatures of highly similar chromophores in living cells