Rheological Properties of Clay Suspensions Treated by Hydrocyclone Process

Suspensions of bentonite clays are usually employed at industrial scale in different processes as drilling fluids as well as adsorbents for removing pollutants in muds or natural waters. For these purposes, avoiding the gravitational settling of the particles is a requirement for achieving a high efficiency and a low cost operation. Unfortunately, the clays in natural deposits are usually mixed with particles of other minerals with similar density, making difficult the separation process by usual gravitational methods. Among the most efficient and lowest cost processes, the separation by hydrocyclone is preferred because of a number of advantages at the industrial scale. In this work we verify, by different experimental methods, the efficiency of this wet separation process for removing impurities in a raw bentonite mineral, and at the same time to transform a calcium bentonite in a sodium one by dissolving sodium carbonate in the liquid phase of the hidrocyclone. Afterwards, we checked by using rheological measurements the best protocol for the preparation of the suspension. We studied the rheological behaviour of clay suspensions, with different degree of impurities removal and with different solid concentration, in order to determine the minimal conditions for obtaining bentonite suspensions that do not suffer from gravitational settling during a long period of time. For this purpose, we investigated the deformation and flow of different suspensions, under steady state and oscillatory shear, and determined when they developed a high enough yield stress and an appropriate elastic response to avoid particle settling. We explain the results in view of the energy of interaction between the different surfaces (faces, edges) of the clay platelets, which favours the formation of a soft gel in which the particles are entrapped in loose flocculi that extent along all the volume of the suspensions.This study was supported by project FIS2013-41821-R (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad, Spain, co-funded by ERDF, European Union). Mariem Mekni Abrougui acknowledges financial support from Tunisian Goverment (fellowship program) and UE (Erasmus program) for her stays in the University of Granada

Generation of membrane-bound catechol-O-methyl transferase deficient mice with disctinct sex dependent behavioral phenotype.

PMID: 28195063Catechol-O-methyltransferase (COMT) has two isoforms: soluble (S-COMT), which resides in the cytoplasm, and membrane-bound (MB-MT), anchored to intracellular membranes. COMT is involved in the O-methylation of L-DOPA, dopamine and other catechols. The exact role of MB-COMT is still mostly unclear. We wanted to create a novel genetically modified mouse model that specifically lacks MB-COMT activity and to study their behavioral phenotype. MB-COMT knock-in mutant mice were generated by introducing two point mutations in exon 2 of the Comt gene (ATGCTG->GAGCTC disabling the function of the P2 promoter and allowing only the P1-regulated S-COMT transcription. The first mutation changes methionine to glutamic acid whereas the second one does not affect coding. The expression of the two COMT isoforms, total COMT activity in several areas of the brain and peripheral tissues and extracellular dopamine concentrations after L-DOPA (10 mg/kg) and carbidopa (30 mg/kg) subcutaneous administration were assessed. A battery of behavioral tests was performed to compare MB-COMT deficient mice and their wild type littermates of both sexes. MB-COMT deficient mice were seemingly normal, bred usually and had unaltered COMT activity in the brain and periphery despite a complete lack of the MB-COMT protein. MB-COMT deficient male mice showed higher extracellular dopamine levels than their wild-type littermates in the striatum, but not in the mPFC. In addition, the MB-COMT deficient male mice exhibited a distinct endophenotype characterized by schizophrenia-related behaviors like aggressive behavior and reduced prepulse inhibition. They also had prolonged immobility in the tail suspension test. Both sexes were sensitized to acute pain and had normal motor activity but disturbed short-term memory. Hence the behavioral phenotype was not limited to schizophrenia-related endophenotype and some behavioural findings were not sex-dependent. Our findings indicate that MB-COMT is critical for behavior, and its function in COMT-dependent brain areas cannot be entirely substituted by the remaining S-COMT.Peer reviewe

REGULATION OF BETA-ADRENOCEPTORS ACTIVITYUSING SYNTHETIC LIGHT-REGULATED MOLECULES

Beta-adrenoceptors (ß-AR) are prototypical G proteincoupled receptors and important pharmacological targets for many diseases. Indeed, a number of approved drugs target these receptors due to their key role on many physiological functions. Among other examples, we encounter ß1-AR antagonists (ß- Blockers), which constitute the first-line therapy for the treatment of heart diseases, and ß2-AR agonists, which act as bronchodilators for the treatment of breathing pathologies. Considering the relevance of these receptors, achieving a reversible and localised control of their activity would provide a powerful tool, both for its research applications and its clinical potential. In this context, photopharmacology arises as a potent approach. Photopharmacology is an emerging field based on the use of synthetic light-regulated molecules to allow reversible spatiotemporal control of target receptors in native tissues. These ligands have the potential to provide a precise and controllable therapeutic action with increased efficacy and reduced side effects. Moreover, the fine regulation on demand of the receptor activation state is of great interest for their study in non-modified cells, tissues and organisms. The present project provides the first proof of concept for beta-adrenoceptor photopharmacology. We first designed and synthesised libraries of lightregulated compounds in order to regulate ß-AR activity with spatiotemporal precision. Subsequent testing highlighted the successful development of compounds with promising pharmacological properties which can be reversibly and irreversibly controlled by light. The discovered molecules enable a fine control of ß-AR in their native environment that will certainly open the door to innovative research procedures and may inspire future personalized therapies targeting these receptors

In vitro and in vivo regulation of ß-Adrenoceptors signaling using synthetic light-regulated molecules

Beta-adrenoceptors (ß-AR) are prototypical G protein-coupled receptors (GPCR) and important pharmacological targets for numerous diseases. Indeed, a number of approved drugs target ß-AR, which are key regulators of many physiological functions. Among other examples, ß1-AR antagonists (known as ß-Blockers) are first-line therapies for the treatment of heart failure, and ß2-AR agonists, which act as bronchodilators, are widely used for the treatment of breathing pathologies. Considering the medical relevance of these receptors, achieving a reversible and localized control of their activity would provide a powerful research and clinical tool. GPCR signaling is currently recognized as a multidimensional process governed by molecular, spatial and temporal components. Uncovering the role of each of these dimensions is crucial to improve our knowledge on cell communication, to understand how different pathways give rise to cellular and physiological effects, and to know how can we interact with biological systems with precision using drugs. Photopharmacology is an emerging field in which light-sensitive molecules are used to control the function of a given target protein in native tissues. The modulation of the target activity is achieved by small, drug-like, photoregulated ligands. By the use of light, both spatial and temporal control of the compound activity can be achieved in unprecedented manners compared to conventional pharmacology. These ligands have the potential to provide highly precise and controllable therapeutic actions that may result in increased efficacies and reduced side effects. Importantly, photopharmacology may allow to gain mechanistic insight on the interplay between the activation time and the receptor location during signaling processes in non-modified cells, tissues and whole organisms. Our research focused on the generation of new molecular tools for beta-adrenoceptors photopharmacology will be presented in this communication. First, several libraries of light-sensitive compounds with the aim to regulate ß-AR activity with spatiotemporal precision were designed and synthesized. Subsequent testing in cell preparations demonstrated the successful development of compounds with promising pharmacological properties, which can be reversibly and irreversibly controlled by light. Among those, several hit compounds were identified as ligands for beta-1 and beta-2 adrenoceptors with low nanomolar activities. These libraries compounds were found to be active enough to become useful photopharmacological tools, so we also performed in vivo experiments to determine their research potential in physiological environments. Indeed, the discovered molecules enabled a fine control of ß-AR in their native environment. We believe that the results of these studies will certainly open the door to innovative research procedures and may inspire future therapies targeting ß-AR

Phase 1 study of Intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection

Background: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. Methods: seventeen patients scheduled for primary tumor resection were enrolled. IT injection of enadenotucirev (CRC only) was administered as a single dose (≤ 3 × 1011 viral particles [vp]) on day 1, followed by resection during days 8-15. IV infusion of enadenotucirev was administered by three separate doses (1 × 1012 vp) on days 1, 3, and 5, followed by resection during days 8-15 (CRC) or days 10-25 (NSCLC, UCC, and RCC). Enadenotucirev activity was measured using immunohistochemical staining of nuclear viral hexon and quantitative polymerase chain reaction for viral genomic DNA. Results: delivery of enadenotucirev was observed in most tumor samples following IV infusion, with little or no demonstrable activity in normal tissue. This virus delivery (by both IV and IT dosing) was accompanied by high local CD8+ cell infiltration in 80% of tested tumor samples, suggesting a potential enadenotucirev-driven immune response. Both methods of enadenotucirev delivery were well tolerated, with no treatment-associated serious adverse events. Conclusions: this study provides key delivery and feasibility data to support the use of IV infusion of enadenotucirev, or therapeutic transgene-bearing derivatives of it, in clinical trials across a range of epithelial tumors, including the ongoing combination study of enadenotucirev with the checkpoint inhibitor nivolumab. It also provides insights into the potential immune-stimulating properties of enadenotucirev. Trial registration: this MOA study was a phase 1, multicenter, non-randomized, open-label study to investigate the administration of enadenotucirev in a preoperative setting (ClinicalTrials.gov: NCT02053220)

Magnetorheology of alginate ferrogels

Magnetorheological (MR) effect is a phenomenon typical of suspensions of magnetizable particles in a liquid carrier, characterized by strong changes of their mechanical properties in response to applied magnetic fields. Its origin is on the migration of magnetized particles and their aggregation into chain-like structures. However, for ferrogels, consisting of dispersions of magnetic particles in a polymer matrix, migration of particles is hindered by the elastic forces of the polymer network, preventing from strong MR effect. Interestingly, we demonstrate in this manuscript that strong MR effect in robustly cross-linked polymer ferrogels is still possible. Experimental results showed enhancement of the storage modulus of more than one order of magnitude for alginate ferrogels containing less than about 10 vol.% of iron particles under moderate magnetic fields. The differential feature of these ferrogels is that, instead of individual particles, the disperse phase consisted of large clusters of iron microparticles homogeneously distributed within the polymer networks. These clusters of magnetic particles were formed at the stage of the preparation of the ferrogels and their presence within the polymer networks had two main consequences. First, the volume fraction of clusters was considerably larger than this of individual particles, resulting in a larger effective volume fraction of solids. Second, since the force of magnetic attraction between magnetic bodies is roughly proportional to the cube of the body size, the existence of such clusters favored inter-cluster interaction under a magnetic field and the appearance of strong MR effect. On this basis, we demonstrated by theoretical modeling that the strong MR effect displayed by the alginate ferrogels of the present work can be quantitatively explained by assuming the existence of large, roughly spherical particle aggregates formed at the stage of the preparation of the ferrogels. Our theoretical model provides a reasonable quantitative prediction of the experimental resultsThis study was supported by project FIS2017-85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). CGV acknowledges financial support by Ministerio de Ciencia, Innovación y Universidades and University of Granada, Spain, for her FPU17/00491 grant. AZ is grateful to the Program of the Ministry of Education and Science of the Russian Federation, projects 02.A03.21.0006, 3.1438.2017/4.6, and 3.5214.2017/6.7 and the Russian Fund of Basic Researches, project 18-08-0017

Experimental Demonstration of a Cognitive Optical Network for Reduction of Restoration Time

This paper presents the implementation and performance evaluation of a cognitive heterogeneous optical network testbed. The testbed integrates the CMP, the data plane and the cognitive system and reduces by 48% the link restoration time. This paper presents the implementation and performance evaluation of a cognitive heterogeneous optical network testbed. The testbed integrates the CMP, the data plane and the cognitive system and reduces by 48% the link restoration time

Caracterización polínica de las mieles en seis municipios del estado de Tabasco, mediante métodos estadísticos.

El objetivo del estudio fue analizar las mieles de diferente origen floral, utilizando  el procedimiento Prinqual. Durante los años 2006, 2007 y 2008 se colectaron 38 muestras de miel en 14 apiarios ubicados en seis municipios del estado de Tabasco. Se realizó un análisis melisopalinológico obteniendo 37 tipos polínicos de importancia, clasificándolas en 23 muestras multiflorales, seis biflorales y nueve monoflorales, posteriormente se estos se sometieron a un análisis de componentes principales, utilizando el procedimiento Prinqual, dando como resultado tres agrupaciones, donde los de Centro, Balancán y Tacotalpa formaron un grupo teniendo la presencia de Mimosa albida Humb. & Bonpl. ex Willd (Fabaceae), que representa el componente principal; por otro lado, los municipios de Cárdenas y Huimanguillo formaron otro grupo teniendo la presencia de Bursera simaruba L. (Burseraceae) y Cecropia obtussifolia Bertol. (Moraceae) y Centla en cambio mostró una clara diferencia con los 5 municipios restantes formando otro grupo teniendo la presencia de Cocos nucifera L. y la familia Poaceae, esto es explicado por la presencia de las especies en el estado