Reciclado de hormigón fresco mediante el uso de adición pelletizante

El retorno del hormigón fresco a la planta de elaboración es un problema económico y medioambiental. Aproximadamente el 2% de la producción de hormigón regresa a la planta y, en la mayoría de los casos, se elimina en gran medida como material de desecho. La producción de bloques, agregados triturados o la separación de sus componentes son algunas de las alternativas informadas para su reciclado. Recientemente se desarrolló una nueva tecnología basada en una adición en polvo de dos componentes que permite que el hormigón fresco se convierta fácilmente en un agregado artificial que puede reincorporarse a la producción de hormigón. En este trabajo se estudiaron las propiedades de los agregados pelletizados (AP) obtenidos a partir de dos formulaciones de hormigón con diferente tamaño máximo nominal de agregados naturales (AN). Asimismo, se evaluaron mezclas de hormigón que tuvieron diferentes niveles de reemplazo de AN por AP en su dosificación. En las formulaciones con sustitución parcial de AN por AP se observó una reducción de alrededor del 20% en la resistencia a la compresión respecto a la muestra control, incluso para porcentajes de sustitución muy elevados (60%). A pesar de la disminución, los hormigones basados en AP cumplen en todos los casos con los requisitos de resistencia y permiten revalorizar un residuo de la industria y cuidar el medio ambiente.Returned fresh mix concrete to the processing plant is an economic and environmental problem. About 2% of concrete production returns to the plant and, in most cases, is largely disposed of as waste material. The production of blocks, crushed aggregates or the separation of their main components are some of the alternatives reported for recycling. Recently, a new technology based on two-component powder additive has been developed, allowing the fresh returned concrete to be easily converted into an artificial aggregate, which can be incorporated into the production of concrete. In this paper, the properties of pelletized aggregates (AP) obtained from two concrete formulations with different maximum nominal natural aggregate size (AN) were studied. Also, concrete mixtures that had different levels of replacement of AN by AP in the formulation were evaluated. In the formulations with partial replacement of AN by AP, a 20% reduction in the compressive strength was observed compared to the control sample, even for very high percentages of substitution (60%). Despite the decrease, AP-based concretes comply in all cases with the resistance requirements and allow to revalue an industrial waste and take care of the environment.Fil: Schust, C.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Ramos, M.. Coarco S.A; ArgentinaFil: Stefani, Pablo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

Reciclado de hormigón fresco mediante el uso de adición pelletizante

El retorno del hormigón fresco a la planta de elaboración es un problema económico y medioambiental. Aproximadamente el 2% de la producción de hormigón regresa a la planta y, en la mayoría de los casos, se elimina en gran medida como material de desecho. La producción de bloques, agregados triturados o la separación de sus componentes son algunas de las alternativas informadas para su reciclado. Recientemente se desarrolló una nueva tecnología basada en una adición en polvo de dos componentes que permite que el hormigón fresco se convierta fácilmente en un agregado artificial que puede reincorporarse a la producción de hormigón. En este trabajo se estudiaron las propiedades de los agregados pelletizados (AP) obtenidos a partir de dos formulaciones de hormigón con diferente tamaño máximo nominal de agregados naturales (AN). Asimismo, se evaluaron mezclas de hormigón que tuvieron diferentes niveles de reemplazo de AN por AP en su dosificación. En las formulaciones con sustitución parcial de AN por AP se observó una reducción de alrededor del 20% en la resistencia a la compresión respecto a la muestra control, incluso para porcentajes de sustitución muy elevados (60%). A pesar de la disminución, los hormigones basados en AP cumplen en todos los casos con los requisitos de resistencia y permiten revalorizar un residuo de la industria y cuidar el medio ambiente.Returned fresh mix concrete to the processing plant is an economic and environmental problem. About 2% of concrete production returns to the plant and, in most cases, is largely disposed of as waste material. The production of blocks, crushed aggregates or the separation of their main components are some of the alternatives reported for recycling. Recently, a new technology based on two-component powder additive has been developed, allowing the fresh returned concrete to be easily converted into an artificial aggregate, which can be incorporated into the production of concrete. In this paper, the properties of pelletized aggregates (AP) obtained from two concrete formulations with different maximum nominal natural aggregate size (AN) were studied. Also, concrete mixtures that had different levels of replacement of AN by AP in the formulation were evaluated. In the formulations with partial replacement of AN by AP, a 20% reduction in the compressive strength was observed compared to the control sample, even for very high percentages of substitution (60%). Despite the decrease, AP-based concretes comply in all cases with the resistance requirements and allow to revalue an industrial waste and take care of the environment.Fil: Schust, C.. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Ramos, M.. Coarco S.A; ArgentinaFil: Stefani, Pablo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation. Originally published in British Journal of Cancer 2009 Vol. 110, No.

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation

Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer

Pancreatic cancer (PC) mobilizes myeloid cells from the bone marrow to the tumor where they promote tumor growth and proliferation. Cancer stem cells (CSCs) are a population of tumor cells that are responsible for tumor initiation. Aldehyde dehydrogenase-1 activity in PC identifies CSCs, and its activity has been correlated with poor overall prognosis in human PC. Myeloid cells have been shown to impact tumor stemness, but the impact of immunosuppressive tumor-infiltrating granulocytic and monocytic myeloid-derived suppressor cells (Mo-MDSC) on ALDH1(Bright) CSCs and epithelial to mesenchymal transition is not well understood. In this study, we demonstrate that Mo-MDSC (CD11b(+)/Gr1(+)/Ly6G(−)/Ly6C(hi)) significantly increase the frequency of ALDH1(Bright) CSCs in a mouse model of PC. Additionally, there was significant upregulation of genes associated with epithelial to mesenchymal transition. We also found that human PC converts CD14(+) peripheral blood monocytes into Mo-MDSC (CD14(+)/HLA-DR(low/−)) in vitro, and this transformation is dependent on the activation of the STAT3 pathway. In turn, these Mo-MDSC increase the frequency of ALDH1(Bright) CSCs and promote mesenchymal features of tumor cells. Finally, blockade of STAT3 activation reversed the increase in ALDH1(Bright) CSCs. These data suggest that the PC tumor microenvironment transforms monocytes to Mo-MDSC by STAT3 activation, and these cells increase the frequency of ALDH1(Bright) CSCs. Therefore, targeting STAT3 activation may be an effective therapeutic strategy in targeting CSCs in PC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-014-1527-x) contains supplementary material, which is available to authorized users

FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation

Genetic and Pharmacological Inhibition of MicroRNA-92a Maintains Podocyte Cell Cycle Quiescence and Limits Crescentic Glomerulonephritis

Crescentic rapidly progressive glomerulonephritis (RPGN) represents the most aggressive form of acquired glomerular disease. While most therapeutic approaches involve potentially toxic immunosuppressive strategies, the pathophysiology remains incompletely understood. Podocytes are glomerular epithelial cells that are normally growth-arrested because of the expression of cyclin-dependent kinase (CDK) inhibitors. An exception is in RPGN where podocytes undergo a deregulation of their differentiated phenotype and proliferate. Here we demonstrate that microRNA-92a (miR-92a) is enriched in podocytes of patients and mice with RPGN. The CDK inhibitor p57Kip2 is a major target of miR-92a that constitutively safeguards podocyte cell cycle quiescence. Podocyte-specific deletion of miR-92a in mice de-repressed the expression of p57Kip2 and prevented glomerular injury in RPGN. Administration of an anti-miR-92a after disease initiation prevented albuminuria and kidney failure, indicating miR-92a inhibition as a potential therapeutic strategy for RPGN. We demonstrate that miRNA induction in epithelial cells can break glomerular tolerance to immune injury

Chemical Probes that Competitively and Selectively Inhibit Stat3 Activation

Signal transducer and activator of transcription (Stat) 3 is an oncogene constitutively activated in many cancer systems where it contributes to carcinogenesis. To develop chemical probes that selectively target Stat3, we virtually screened 920,000 small drug-like compounds by docking each into the peptide-binding pocket of the Stat3 SH2 domain, which consists of three sites—the pY-residue binding site, the +3 residue-binding site and a hydrophobic binding site, which served as a selectivity filter. Three compounds satisfied criteria of interaction analysis, competitively inhibited recombinant Stat3 binding to its immobilized pY-peptide ligand and inhibited IL-6-mediated tyrosine phosphorylation of Stat3. These compounds were used in a similarity screen of 2.47 million compounds, which identified 3 more compounds with similar activities. Examination of the 6 active compounds for the ability to inhibit IFN-γ-mediated Stat1 phosphorylation revealed that 5 of 6 were selective for Stat3. Molecular modeling of the SH2 domains of Stat3 and Stat1 bound to compound revealed that compound interaction with the hydrophobic binding site was the basis for selectivity. All 5 selective compounds inhibited nuclear-to-cytoplasmic translocation of Stat3, while 3 of 5 compounds induced apoptosis preferentially of breast cancer cell lines with constitutive Stat3 activation. Thus, virtual ligand screening of compound libraries that targeted the Stat3 pY-peptide binding pocket identified for the first time 3 lead compounds that competitively inhibited Stat3 binding to its pY-peptide ligand; these compounds were selective for Stat3 vs. Stat1 and induced apoptosis preferentially of breast cancer cells lines with constitutively activated Stat3