908 research outputs found

    ANÁLISIS DEL SISTEMA ACTUAL DE UN SECADERO DE BLOQUES DE ARCILLA Y PROPUESTA DE MEJORAMIENTO

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    En las pequeñas y medias empresas de la región de la provincia de Ocaña, procesadoras de materiales cerámicos de la región, los procesos productivos sonartesanales y de mediana tecnificación respectivamente, ya que se han antenido en el tiempo sin aplicar mecanismos que desarrollen procesos tecnológicos. Por tal motivo se hace necesaria la optimización de procesos que hagan más eficiente el desarrollo de productos, disminuyendo perdidas de fabricación. Para este caso en específico, se describe cada uno de los procesos utilizados en el análisis y el estudio realizado en una ladrillera de las empresas de la región, en la etapa de mejoramiento del sistema de extracción de humedad dentro de las cámaras de secado artificial, y en la cual se presentan las mayores pérdidas del producto. De acuerdo a los análisis realizados tanto teóricos como por simulación en esta investigación se presentó una propuesta económica  de implementar un sistema mecánico o extractor axial, sin alterar el comportamiento de las variables que rigen el sistema según las curvas de secado o de Bigot, (temperatura, humedad relativa y contracción del material)

    Simple isophthalamides/dipicolineamides as active transmembrane anion transporters

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    Eight N,N´-diarylisophthalamide/dipicolineamide derivatives have been synthesised and fully characterised, both in solution and in the solid state. The transmembrane anion transport properties of these compounds have been studied by chloride-selective electrode and fluorescence experiments. The substitution pattern of the aromatic moieties determines the transport properties of these systems, with those containing electron-withdrawing groups in their structures being the most active ones of the series.Consejería de Educación de la Junta de Castilla y León (project BU075G19

    Multicamera Optical Tracker Assessment for Computer Aided Surgery Applications

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    Image-guided interventions enable the surgeon to display the position of instruments and devices with respect to the patient's imaging studies during surgery by means of a tracker device. Optical trackers are commonly chosen for many surgical applications when high accuracy and robustness are required. OptiTrack is a multicamera optical tracker whose number of sensors and their spatial configuration can be adapted to the application requirements, making it suitable for surgical settings. Nonetheless, no extensive studies of its accuracy are available. The purpose of this paper was to evaluate an eight-camera optical tracker in terms of accuracy, miscalibration sensitivity, camera occlusions, and tool detection in a feasible clinical setup. We studied the tracking accuracy of the system using a robotic arm (~μm precision) as the gold standard, a single reflective marker, and various tracked objects while the system was installed in an operating room. Miscalibration sensitivity was 0.16°. Mean target error was 0.24 mm for a single marker, decreasing to 0.05 mm for tracked tools. Single-marker error increased up to 1.65 mm when five cameras where occluded although 75% of the working volume showed an error lower than 0.23 mm. The accuracy was sufficient for navigating the collimator in intraoperative electron radiation therapy, improving redundancy and allowing large-working volumes. The tracker assessment we present and the validated miscalibration protocol are important contributions to image-guided surgery, where the choice of the tracker is critical and the knowledge of the accuracy in situations of camera occlusion is mandatory during surgical navigation

    Small molecule anion carriers facilitate lactate transport in model liposomes and cells

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    An excessive production of lactate by cancer cells fosters tumor growth and metastasis. Therefore, targeting lactate metabolism and transport offers a new therapeutic strategy against cancer, based on dependency of some cancer cells for lactate as energy fuel or as oncogenic signal. Herein we present a family of anionophores based on the structure of click-tambjamines that have proved to be extremely active lactate carriers across phospholipid membranes. Compound 1, the most potent lactate transmembrane carrier, was studied in HeLa cells. The use of a monocarboxylate transporters (MCTs) inhibitor proved that 1 is an active lactate transporter in living cells, confirming the results obtained in phospholipid vesicles. Moreover, an additive effect of compound 1 with cisplatin was observed in HeLa cells. Identification of active lactate anionophores working in living cells opens up ways to exploit this class of compounds as molecular tools and drugs addressing dysregulated lactate metabolism

    Small molecule anion transporters display in vitro antimicrobial activity against clinically relevant bacterial strains

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    Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains. This type of compound offers promise as a strategy to develop novel antibacterial agents

    Click-tambjamines as efficient and tunable bioactive anion transporters

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    A novel class of transmembrane anion carriers, the click-tambjamines, display remarkable anionophoric activities in model liposomes and living cells. The versatility of this building block for the generation of molecular diversity offers promise to develop future drugs based on this design.European Union’s Horizon 2020 research and innovation programme (TAT-CF project, grant agreement 667079), Instituto de Salud Carlos III (Grant PI18/00441) (co-funded by the European Regional Development Fund (ERDF), a way to build Europe) and “La Caixa” Foundation and Caja Burgos Foundation (CAIXAUBU004

    A Novel Late-Stage Autophagy Inhibitor That Efficiently Targets Lysosomes Inducing Potent Cytotoxic and Sensitizing Effects in Lung Cancer

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    Simple Summary Lung cancer is the main cause of cancer-related deaths worldwide, mainly due to treatment resistance. For that reason, it is necessary to develop novel therapeutic strategies to overcome this phenomenon. The aim of our study was to design and characterize a synthetic anionophore, LAI-1, that would be able to efficiently disrupt lysosomal activity, leading to autophagy blockage, one of the most important resistance mechanisms in cancer cells. We confirmed that LAI-1 selectively localized in lysosomes, deacidifying them. This effect produced a blockage of autophagy, characterized by an abrogation of autophagosomes and lysosomes fusion. Moreover, LAI-1 produced cell death in lung cancer cells from different histological subtypes, inducing cytotoxicity more efficiently than other known autophagy inhibitors. Finally, LAI-1 was evaluated in combination therapy, showing sensitization to the first-line chemotherapeutic agent cisplatin. Altogether, LAI-1 is a novel late-stage autophagy inhibitor with potential therapeutic applications in tumors with cytoprotective autophagy. Overcoming resistance is one of the most challenging features in current anticancer therapy. Autophagy is a cellular process that confers resistance in some advanced tumors, since it enables cancer cells to adapt to stressful situations, such as anticancer treatments. Hence, the inhibition of this cytoprotective autophagy leads to tumor cells sensitization and death. In this regard, we designed a novel potent anionophore compound that specifically targets lysosomes, called LAI-1 (late-stage autophagy inhibitor-1), and evaluated its role in blocking autophagy and its potential anticancer effects in three lung cancer cell lines from different histological subtypes. Compared to other autophagy inhibitors, such as chloroquine and 3-Methyladenine, the LAI-1 treatment induced more potent anticancer effects in all tested cancer cells. LAI-1 was able to efficiently target and deacidify lysosomes, while acidifying cytoplasmic pH. Consequently, LAI-1 efficiently blocked autophagy, indicated by the increased LC3-II/I ratio and p62/SQSTM1 levels. Moreover, no colocalization was observed between autophagosomes, marked with LC3 or p62/SQSTM1, and lysosomes, stained with LAMP-1, after the LAI-1 treatment, indicating the blockage of autophagolysosome formation. Furthermore, LAI-1 induced cell death by activating apoptosis (enhancing the cleavage of caspase-3 and PARP) or necrosis, depending on the cancer cell line. Finally, LAI-1 sensitized cancer cells to the first-line chemotherapeutic agent cisplatin. Altogether, LAI-1 is a new late-stage autophagy inhibitor that causes lysosomal dysfunction and the blockage of autophagolysosome formation, as well as potently induces cancer cell death and sensitization to conventional treatments at lower concentrations than other known autophagy inhibitors, appearing as a potential new therapeutic approach to overcome cancer resistance

    Reemplazo de la harina de pescado con gluten de maíz en dietas de juveniles de trucha arcoíris (Oncorhynchus mykiss): efectos en crecimiento y otros parámetros fisiológicos

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    Background: Plant-origin meals have been proposed as an alternative to fishmeal as a source of protein in diets for rainbow trout (Oncorhynchus mykiss) and one suggested alternative is corn gluten. Goals: Determine the effects on the growth and other physiological parameters of rainbow trout juveniles fed diets made with corn gluten as substitute for fishmeal. Methods: Three diets that substituted corn gluten in ratios of 50, 75, and 100% (G50%, G75% and G100%, respectively) for fishmeal were fed during 90 days to juveniles initially weighing14.7 ± 0.2 g (mean ± standard error). We measured growth performance, oxygen consumption, P and N excretion, protein and lipid contents in muscle and liver, as well the number of lymphocytes and burst activity of the kidney macrophage. Results: Growth performance (weight gain and specific growth rate) decreased as corn gluten increased in the diet. The organisms fed with G75% and G100% diets had a significantly lower de­position of protein in the muscle with respect to the other groups, while lipid deposition increased in the same tissue. Increasing levels of the corn gluten in the diet caused increased oxygen consumption and N ammonium excretion but did not affect the number of lymphocyte and the macrophage activity. Conclusions: Corn gluten may be used at a substitution level up to 50% in diets for juvenile rainbow trout.Antecedentes: Las harinas de origen vegetal, como el gluten de maíz, se han propuesto en dietas para tru­cha arcoíris (Oncorhynchus mykiss) como fuente alternativa de proteína en lugar de las harinas de pescado. Objetivos: Determinar el efecto en el crecimiento y otros parámetros fisiológicos de juveniles de trucha arcoíris alimentadas con dietas elaboradas a base de gluten de maíz como sustituto de harina de pescado. Métodos: Durante un período de 90 días se administraron tres dietas con sustituciones de 50, 75 y 100% de gluten de maíz (G50%, G75% y G100%, respectivamente) utilizando gluten de maíz fueron administradas por un período de 90 días a juveniles con peso inicial de 14.7 ± 0.2 g (promedio ± error estándar). Se determinó el crecimiento, el consumo de oxígeno, la excreción de P y N, el contenido de proteína y lípidos en músculo e hígado, así como el número de linfocitos y la actividad explosiva de los macrófagos del riñón. Resultados: Se observó una disminución en el crecimiento (ganancia en peso y tasa de crecimiento específico) confor­me aumentó la inclusión del gluten de maíz en la dieta. Los organismos alimentados con G75% y G100% presentaron un contenido significativamente menor de proteína en el tejido muscular respecto al otro grupo, mientras que, de lo contrario, hubo un aumento en la deposición de lípidos del mismo tejido. El aumento de gluten de maíz incrementó el consumo de oxígeno y la excreción de nitrógeno amoniacal, pero no afectó al número de linfocitos ni la actividad de macrófagos. Conclusiones: Se puede incorporar hasta una 50% de gluten de maíz en dietas para juveniles de trucha arcoíris

    Filósofos de la Intemperie (III): el cinismo en su contexto

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    Proyecto dedicado al estudio y análisis de la corriente de filosofía cínica y su contexto histórico-cultural a través de actividades vertebradas alrededor de un seminario que encara este curso su tercera edición

    RET Fusion Testing in Patients With NSCLC: The RETING Study

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    Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identi fication of RET fusions remains a dif ficult challenge. Most guidelines encourage the upfront use of next -generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion -positive NSCLC (n 1 / 4 38) to obtain real -world data. In addition to RNA -based NGS (the criterion standard method), all positive specimens underwent break -apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGSpositive but FISH -negative samples contained a KIF5B(15)RET(12) fusion. The three RET fusions not identi fied with RT-PCR were AKAP13(35)-RET(12) , KIF5B(24)-RET(9) and KIF5B(24)-RET(11) . All three false -negative RT-PCR cases were FISH -positive, exhibited a typical break -apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false -negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
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