11 research outputs found
Influencia de la geometría urbana en la demanda energética anual para enfriamiento. Estudio de caso Camagüey
In order to analyse the influence of the urban geometry in the energy demand for air conditioning (cooling) of the buildings became elaborate an Excel application that enables forecasting the energy demand of buildings from your Shape Factor, coefficient defined by geometric parameters (volume and exposed surface). For this, it was elaborated with different degrees of exposition, generic models of buildings of three urban morphologies (compact, semi-compact and open) representative of development periods historic of Camagüey city. With the help of energetic simulations using EnergyPlus vr.8.8 software the forecast of your demand was calculated. With the values of the results and by means of multivariable regression, in the software Statgraphics Centurion XV, obtained him an equation that was utilised to elaborate the Excel application. This tool constitutes an aid to the designer to forecast the energetic performance of her project with the aim to better energetic solutions from the first stages of conception of the building. At last, in order to show your application, it was executed a mapification morfo-energetic of the three urban samples of Camaguey in 3D, in order to characterise the influence of the urban geometry in the energy demand for air conditioning.Para evaluar la influencia de la geometría urbana en la demanda energética por climatización (enfriamiento) de los edificios se elaboró una aplicación de cálculo en Excel que permite pronosticar la demanda energética de edificios a partir de su “Factor de Forma”, coeficiente definido por parámetros geométricos (volumen y superficie expuesta). Para esto se elaboraron —con diferentes grados de exposición— modelos genéricos de edificios de tres morfologías urbanas (compacta, semicompacta y abierta) representativas de períodos históricos de desarrollo de la ciudad de Camagüey. Con la ayuda de simulaciones energéticas mediante el programa EnergyPlus vr.8.8 se calculó el pronóstico de sus demandas. Con los valores de los resultados y mediante regresión multivariable, en el software Statgraphics Centurion XV, se obtuvo una ecuación que fue utilizada para elaborar la mencionada aplicación Excel. Esta herramienta constituye una ayuda al proyectista para pronosticar el desempeño energético de su proyecto con vistas a lograr mejores soluciones energéticas desde las primeras etapas de concepción del edificio. Finalmente, para mostrar su aplicación, se realizó una mapificación morfo-energética de las tres muestras urbanas de Camagüey en 3D, con el propósito de caracterizar la influencia de la geometría urbana en la demanda de energía por climatización
Development of a High-Throughput Calcium Mobilization Assay for CCR6 Receptor Coupled to Hydrolase Activity Readout
CCR6 is a chemokine receptor highly implicated in inflammatory diseases and could be a potential therapeutic target; however, no therapeutic agents targeting CCR6 have progressed into clinical evaluation. Development of a high-throughput screening assay for CCR6 should facilitate the identification of novel compounds against CCR6. To develop a cell-based assay, RBL-2H3 cells were transfected with plasmids encoding β-hexosaminidase and CCR6. Intracellular calcium mobilization of transfected cells was measured with a fluorescent substrate using the activity of released hexosaminidase as readout of the assay. This stable, transfected cell showed a specific signal to the background ratio of 19.1 with low variability of the signal along the time. The assay was validated and optimized for high-throughput screening. The cell-based calcium mobilization assay responded to the specific CCR6 ligand, CCL20, in a dose-dependent manner with an EC50 value of 10.72 nM. Furthermore, the assay was deemed robust and reproducible with a Z’ factor of 0.63 and a signal window of 7.75. We have established a cell-based high-throughput calcium mobilization assay for CCR6 receptor. This assay monitors calcium mobilization, due to CCR6h activation by CCL20, using hexosaminidase activity as readout. This assay was proved to be robust, easy to automate and could be used as method for screening of CCR6 modulators
Covalent Immobilization of Antibodies through Tetrazine-TCO Reaction to Improve Sensitivity of ELISA Technique
This research was funded by Compra Publica Precomercial, Reference 2012/000069, Ministerio de Economia y Competitividad, Espana. ONCOVER project: Volatile compound detection system for early cancer diagnosis.Enzyme-linked immunosorbent assay (ELISA) is routinely used to detect biomolecules
related to several diseases facilitating diagnosis and monitoring of these, as well as the possibility
of decreasing their mortality rate. Several methods have been carried out to improve the ELISA
sensitivity through antibodies immobilization on the microtiter plates. Here, we have developed
a strategy of antibodies immobilization to improve the ELISA sensitivity increasing the antibody
density surface through the tetrazine (Tz)-trans-cyclooctene (TCO) reaction. For this, we prepared
surfaces with tetrazine groups while the captured antibody was conjugated with TCO. The tetrazine
surfaces were prepared in two different ways: (1) from aminated plates and (2) from Tz-BSA-coated
plates. The surfaces were evaluated using two sandwich ELISA models, one of them using the
low-affinity antibody anti-c-myc as a capture antibody to detect the c-myc-GST-IL8h recombinant
protein, and the other one to detect the carcinoembryonic human protein (CEA). The sensitivity
increased in both surfaces treated with tetrazine in comparison with the standard unmodified surface.
The c-myc-GST-IL8h detection was around 10-fold more sensible on both tetrazine surfaces, while
CEA ELISA detection increased 12-fold on surfaces coated with Tz-BSA. In conclusion, we show
that it is possible to improve the ELISA sensitivity using this immobilization system, where capture
antibodies bond covalently to surfaces.Compra Publica Precomercial, Ministerio de Economia y Competitividad, Espana 2012/00006
Extra-Virgin Olive Oil Modifies the Changes Induced in Non-Nervous Organs and Tissues by Experimental Autoimmune Encephalomyelitis Models
This study reveals the existence of oxidative stress (reactive oxygen species (ROS)) in non-nervous organs and tissues in multiple sclerosis (MS) by means of a model of experimental autoimmune encephalomyelitis (EAE) in rats. This model reproduces a similar situation to MS, as well as its relationship with intestinal microbiota starting from the changes in bacterial lipopolysaccharide levels (LPS) in the outer wall of the gram-negative bacteria. Finally, the administration of extra-virgin olive oil (EVOO), hydroxytirosol (HT), and oleic acid (OA) exert beneficial effects. Twenty-five Dark Agouti two-month-old male rats, weighing around 190 g, were distributed into the following groups: Control, EAE (experimental autoimmune encephalomyelitis group), EAE + EVOO, EAE + HT, and EAE + OA. The glutathione redox system with the EAE was measured in heart, kidney, liver, and small and large intestines. The LPS and the correlation with oxidative stress in the small and large intestines were also investigated. The results showed that (1) the oxidative damage in the EAE model affects non-nervous organs and tissues; (2) The LPS is related to inflammatory phenomena and oxidative stress in the intestinal tissue and in other organs; (3) The administration of EVOO, HT, and OA reduces the LPS levels at the same time as minimizing the oxidative damage; (4) EVOO, HT, and OA improve the disease’s clinical score; and (5) on balance, EVOO offers a better neuroprotective effect
Effects of Virgin Olive Oil Phenolic Compounds on LDL Oxidation and Vasorelaxation Activity
This study examined the efficacy of virgin olive oil phenolic extract and other phenolic compounds (oleuropein, caffeic acid) in preventing oxidative modifications of human low density lipoprotein oxidised by CuCl2. The vasorelaxant effect of these compounds on rat aortic ring with and without functional endothelium is also discussed. Olive oil phenolic extract, caffeic acid and oleuropein increased the lag time of conjugated diene formation in a concentration-dependent manner. Moreover, phenolic extract produced a vasorelaxant effect that persisted in denuded aorta and after inhibition of nitric oxide synthase by N-methyl-L-arginine (L-NMMA) or methylene blue. Oleuropein did not produce a relaxant effect, whereas caffeic acid produced partial relaxation at concentration 0.5 g/L
Amino terminal recognition by a CCR6 chemokine receptor antibody blocks CCL20 signaling and IL-17 expression via β-arrestin.
CCR6 chemokine receptor is an important target in inflammatory diseases. Th17 cells express CCR6 and a number of inflammatory cytokines, including IL-17 and IL-22, which are involved in the propagation of inflammatory immune responses. CCR6 antagonist would be a potential treatment for inflammatory diseases such as psoriasis or rheumatoid arthritis. The aim of this study is to develop an antagonistic monoclonal antibody (mAb) against human CCR6 receptor (hCCR6). We generate monoclonal antibodies against hCCR6 immunizing Balb/c mice with hCCR6 overexpressing cells. The antibodies were tested by flow cytometry for specific binding to hCCR6, cloned by limiting dilution and resulted in the isolation and purification monoclonal antibody 1C6. By ELISA and flow cytometry, was determined that the antibody obtained binds to hCCR6 N-terminal domain. The ability of 1C6 to neutralize hCCR6 signaling was tested and we determined that 1C6 antibody were able to block response in β-arrestin recruitment assay with IC50 10.23 nM, but did not inhibit calcium mobilization. In addition, we found in a chemotaxis assay that 1C6 reduces the migration of hCCR6 cells to their ligand CCL20. Finally, we determined by RT-qPCR that the expression of IL-17A in Th17 cells treated with 1C6 was inhibited. In the present study, we applied whole cell immunization for successfully obtain an antibody that is capable to neutralize hCCR6 signaling and to reduce hCCR6 cells migration and IL-17 expression. These results provide an efficient approach to obtain therapeutic potential antibodies in the treatment of CCR6-mediated inflammatory diseases
Benzo-heterociclos de seis miembros con átomos de oxígeno y nitrógeno con actividad antitumoral
Número de publicación: 2648538Número de solicitud: 20160030714Benzo-heterociclos de seis miembros con átomos de oxígeno y nitrógeno con actividad antitumoral. La presente invención se refiere a una nueva familia de benzo-heterociclos de seis miembros con átomos de oxígeno y nitrógeno, unidos a purinas, a halógenos y a triazoles sustituidos que son útiles en terapia frente al cáncer, en particular en terapias cuya diana terapéutica son las células madre cancerígenas. La invención también describe el procedimiento de síntesis de dichos compuestos.Universidad de GranadaCanvax Biotech S.LUniversidad de Jaé
Clinical and Neurochemical Effects of Transcranial Magnetic Stimulation (TMS) in Multiple Sclerosis: A Study Protocol for a Randomized Clinical Trial
Background: Transcranial Magnetic Stimulation (TMS) is a technique based on the principles of electromagnetic induction. It applies pulses of magnetic radiation that penetrate the brain tissue, and it is a non-invasive, painless, and practically innocuous procedure. Previous studies advocate the therapeutic capacity of TMS in several neurodegenerative and psychiatric processes, both in animal models and in human studies. Its uses in Parkinson's disease, Alzheimer's disease and in Huntington's chorea have shown improvement in the symptomatology and in the molecular profile, and even in the cellular density of the brain. Consequently, the extrapolation of these TMS results in the aforementioned neurodegenerative disease to other entities with etiopathogenic and clinical analogy would raise the relevance and feasibility of its use in multiple sclerosis (MS). The overall objective will be to demonstrate the effectiveness of the TMS in terms of safety and clinical improvement, as well as to observe the molecular changes in relation to the treatment. Methods and Design: Phase II clinical trial, unicentric, controlled, randomized, single blind. A total of 90 patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) who meet all the inclusion criteria and do not present any of the exclusion criteria that are established and from which clinically evaluable results can be obtained. The patients included will be assigned under the 1:1:1 randomization formula, constituting three groups for the present study: 30 patients treated with natalizumab + white (placebo) + 30 patients treated with natalizumab + TMS (1 Hz) + 30 patients treated with natalizumab + TMS (5 Hz). Discussion: Results of this study will inform on the efficiency of the TMS for the treatment of MS. The expected results are that TMS is a useful therapeutic resource to improve clinical status (main parameters) and neurochemical profile (surrogate parameters); both types of parameters will be checked. Ethics and Dissemination: The study is approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04062331). Dissemination will include submission to a peer-reviewed journal, patients, associations of sick people and family members, healthcare magazines and congress presentations. Trial Registration: ClinicalTrials.gov ID: NCT04062331 (registration date: 19th/ August/2019). Version Identifier: EMTr-EMRR, ver-3, 21/11/2017.Ye