Lipid and Janus nanoparticles for active delivery

The following synthesis is based on the paper „Production of large quantities of „Janus“ nanoparticles using wax-in-water emulsions“ published by Ravaine et al.[1]In two beakers, 0.2 g of the synthesized silica particles were added to a solution of ethanol/water (6.7 % w/w, 100 mL), stirred and heated at 65 °C. To the suspensions were added 0.0220 g (Sample 1) or 0.0302 g (Sample 2) of cetyltrimethylammonium bromide (CTAB), respectively, and afterwards 6.682 g (for Sample 1) and 6.698 g (for Sample 2) of paraffin. After the paraffin was melted, the mixture was submitted to vigorous stirring by means of a homogenizer by 10000 rpm for 90 s. The emulsions were allowed to cool down to room temperature over night in order to get solid droplets of paraffin wax. For functionalization of the particles two solutions of 8 mL EtOH and NH4OH (7 % v/v) with 2.1 mL aminopropyltriethoxysilane (APTES) were prepared and added to both emulsions. After 12 h the solid wax droplets were filtrated, washed 3 times with ethanol, dissolved in DCM and heated till the wax was melted. The mixture was filtrated to receive the Janus particles as a white-beige powder (Samples 1 and 2).To prove the correctness of the procedure and as a result the existence of Janus particles, the particles, in a solution of 0.2 mL of water and ethanol (8:2), were mixed with 0.2 mL of a gold nanoparticle[2] (stabilized by citrate) suspension. The samples were analyzed by TEM. The synthesized silica particles exhibit a diameter of 100 nm, which can be seen in the following pictures (Fig. 1). It could be shown that the silica particles stayed in the water-phase in the DCM-water dual-phase-system, which shows that the synthesized particles are hydrophilic and not hydrophobic. It can be seen that in both samples (Samples 1 and 2, Fig. 2) the gold particles were bound to the functionalized silica particles, whereas sample 2 looks like a Janus particle (Fig. 2, right side). Unfortunately, in both cases the distribution of the gold particles is not very homogeneous and dense like it could be shown in the literature.[1], [2] Because the TEM samples were not completely dry, water can be seen in form of shadows around the particles.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Capacity Limits of Spectrum-Sharing in Hoyt (Nakagami-q) Fading Channels

A channel capacity analysis is presented in this work for a spectrum-sharing cognitive radio link in which the fading experienced by the signal is modeled with the Hoyt (Nakagami-q) distribution. Based on a novel formulation of the squared Hoyt distribution derived by the authors, simple expressions for the capacity of the secondary link in a number of scenarios of interest are derived, which are given in terms of easy-to-compute finite-range integrals of elementary functions. The effect of fading severity in the secondary transmitter-primary receiver (ST-PR) and secondary transmitter-secondary receiver (ST-SR) links, and the impact of different antenna gains on the system performance are analyzed. We show that in the presence of severe fading for the ST-PR link, the capacity of the ST-SR link is increased.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. MINECO. Fondos FEDER. European Union Marie-Curie COFUND U-mobility program

Synthesis and study of biological activity of tetrahydro-1H-[3]-benzazepines

The 3-Benzazepines are an important class of compounds in drug discovery due to their biological activity such as analgesic, antihypertensive or anticancer properties as well as dopaminergic or antidopaminergic activity. In particular, the tetrahydro-1H-[3]- benzazepine is a common skeleton in a number of natural and pharmaceutical products. As consequence of the interesting biological properties, derivatives of the tetrahydro-1H-[3]-benzazepines, especially the 1-aryl substituted have been synthesized by different routes and evaluated their pharmacologic activity. [1,2] The stereoselective synthetic approaches of tetrahydro-1H-[3]-benzazepine have focused on ring enlargements, as the Stevens rearrangement (SR) which is a good regio- and diastereoselective synthetic methodology. In my research group, the reaction conditions to synthesize tetrahydro-1H-[3]-benzazepines 1,2-disubstituted by via SR from tetrahydroisoquinolinium salts conveniently functionalized have been optimized. [3,4] This methodology allowed us to obtain a wide variety of tetrahydro-1H-[3]- benzazepines 1,2-disubstituted with different substituents at A-ring (Cl, OMe) and the C-1 (-C6H4X, X = H, OMe, Cl, NO2, NMe2, NH2, SMe) and C-2 (Electron-withdrawing groups) positions. The demethylation of the synthesized tetrahydroisoquinolines and tetrahydro-1H-[3]-benzazepines 1,2-disubstituted, lead us to get catechol structure, an important requirement for their dopaminergic activity. We have studied the dopaminergic activity of the synthesized compounds by radioligand binding assays, establishing a structure-activity relationships. Literature: [1] A. Gini, Adv. Synth. Catal. 2016, 358, 4049. [2] H. Damsen, Eur. J. Org. Chem. 2015, 36, 7880. [3] M. Valpuesta, Eur. J. Org. Chem. 2010, 23, 4393. [4] M. Ariza, Eur. J. Org. Chem. 2011, 32, 6507.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of bioactive compounds. Studies of their attachment to nanoparticles

The 1-aryl tetrahydroisoquinolines have attracted great attention in medicinal chemistry due to their biological activity. These compounds present antitumor, anti-HIV and antibacterial activities. Several analogues of 1-aryl tetrahydroisoquinoline are used for the treatment of neurodegenerative diseases such as Parkinson´s and Alzheimer´s diseases since also act as dopaminergic antagonists and N-methyl-D-aspartate receptor antagonist. [1] The 1-substituted tetrahydro-3-benzazepines have also been studied for their affinity to the Phencylclidine binding site of the NMDA receptor as well as for their affinity to the dopaminergic receptors. [2] In the last years, various methods have been carried out to satisfy the demand of novel tetrahydroisoquinolines and tetrahydro-3-benzazepines. We have synthesized nor-1-aryl tetrahydroisoquinolines with different substituents in the aryl group of C-1 (H, NMe2, SMe, NO2, NH2). In addition to this, we have performed the synthesis of nor-tetrahydro-3-benzazepinas by different routes, obtaining the best results via opening of epoxides by arylphenethylamines and subsequent cyclization. The nor-tetrahydroisoquinolines and nor-tetrahydro-3-benzazepines have been derivatized to obtain appropiate adsorbates which can be attached to nanoparticles. This fact is crutial in drug delivery systems as well as in the improvement of the biocompatibility of these compounds. Literature: [1] Toshiaki Saitoh, Eur. J. Med. Chem. 2006, 41, 241. Mattias Ludwig, Eur. J. Med. 2006, 41, 1003. [2] Olaf Krull, Bioorg. Med. Chem. 2004, 12, 1439.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Generalized MGF of Beckmann Fading with Applications to Wireless Communications Performance Analysis

The Beckmann distribution is a general multipath fading model for the received radio signal in the presence of a large number of scatterers, which can thence be modeled as a complex Gaussian random variable where both the in-phase and quadrature components have arbitrary mean and variance. However, the complicated nature of this distribution has prevented its widespread use and relatively few analytical results have been reported for this otherwise useful fading model. In this paper, we derive a closed-form expression for the generalized moment-generating function (MGF) of the signal-to-noise ratio (SNR) of Beckmann fading, which permits to circumvent the inherent analytical complexity of this model. This is a new and useful result, as it is key for evaluating several important performance metrics of different wireless communication systems and also permits to readily compute the moments of the output SNR. Thus, we obtain simple exact expressions for the energy detection performance in Beckmann fading channels, both in terms of the receiver operating characteristic (ROC) curve and of the area under ROC curve. We also analyze the outage probability in interference limited systems affected by Beckmann fading, as well as the outage probability of secrecy capacity in wiretap Beckmann fading channels. Monte Carlo simulations have been performed to validate the derived expressions.Universidad de Málaga. Campus de Excelencia Internacional. Andalucía Tech

Tripod-shaped penta (p-phenylene)s for the functionalization of silicon surfaces

In order to obtain nanostructured thin films to be used in biosensor devices, several chemical functionalization methods have been developed, such as Click chemistry or Suzuki carbon-carbon coupling reactions on surfaces.1 With the aim to control the orientation and spacing between grafted functional groups on a surface, tripodal oligo (p-phenylene)s have become the ideal anisotropic adsorbates due to their shape-persistent and self-standing characteristics.2 Here we report the synthesis and characterization of several tripod-shaped oligo(p-phenylene)s molecules with legs composed of five phenylene units, compounds 1, 2 and 3. In these structures, each leg is end-capped with an NH-Boc, NH2 and N3 group, respectively. The functional arm contains an acetylene group. The presented synthesis has as key step the Pd-catalyzed Suzuki cross-coupling reaction. In particular, a iodine derivative from the silicon core molecule reacts with the appropriate tetra(p-phenylene) boron derivative, thus generating the final tripod-shaped structure. The azide end-capped leg in 3 is specifically designed for its covalent incorporation on alkynyl terminated silicon surfaces by an easy and reproducible way. As a preliminary study, we present the alkynyl-functionalized silicon wafers nanostructuration with tripod 3 through the cooper catalyzed alkyne-azide cycloaddition (CuAAC) click reaction.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Amygdala and emotional learning in vertebrates: A comparative perspective

Gobierno de España SI2009-12761Gobierno de España RyC2006/128

Animal models of maladaptive traits: disorders in sensorimotor gating and attentional quantifiable responses as possible endophenotypes

Traditional diagnostic scales are based on a number of symptoms to evaluate and classify mental diseases. In many cases, this process becomes subjective, since the patient must calibrate the magnitude of his/her symptoms and therefore the severity of his/her disorder. A completely different approach is based on the study of the more vulnerable traits of cognitive disorders. In this regard, animal models of mental illness could be a useful tool to characterize indicators of possible cognitive dysfunctions in humans. Specifically, several cognitive disorders such as schizophrenia involve a dysfunction in the mesocorticolimbic dopaminergic system during development. These variations in dopamine levels or dopamine receptor sensibility correlate with many behavioral disturbances. These behaviors may be included in a specific phenotype and may be analyzed under controlled conditions in the laboratory. The present study provides an introductory overview of different quantitative traits that could be used as a possible risk indicator for different mental disorders, helping to define a specific endophenotype. Specifically, we examine different experimental procedures to measure impaired response in attention linked to sensorimotor gating as a possible personality trait involved in maladaptive behaviors.Ministerio de Economía y Competitividad PSI2012- 3244

The videoconference system as a way to serve students with absenteeism for medical reasons

This educational innovation is aimed at students who are forced to interrupt their schooling process for a period of time due to a medical issue. Its goal is to minimize students’ loss of knowledge, skills or abilities. To achieve this goal, we propose the use of a classroom videoconferencing device whereby different sessions can be viewed, either from home or from the hospital, by students who cannot attend class. Sessions can be watched either synchronously (online or live display), enabling students to follow the overall progress of the sesión and participate in different activities in real time; or asynchronously (display on demand) when real-time display is not an option, by recording the session so that students watch it once the class is over. This system can be integrated into any learning platform so that students can self-organize and do assignments all activities more easily

Thermorresponsive magnetic nanoparticles as target drug delivery for cancer treatment

In this research, temperature sensitive microgels with magnetic core for controlled release of 5-fluoruracil was synthesized. Magnetic nanoparticles (Fe3O4) were prepared by coprecipitation method and the surface was functionalized by acrylic acid. Polymer poly(N-isopropylacrylamide) (PNIPAM) were grown by free radical polymerization in presence of cross-liker and initiator. The size of the polymer was manipulated by changing the mole percent of the crosslinker and evaluated for their morphology (TEM), particle size, zeta potential, loading efficiency, drug content and drug release. Furthermore, microgels were tagged with FITC, a fluorochrome which could be applied for cell imaging. Cytotoxicity studies revealed that the microgels were not toxic. These complex nanoparticles (Fe3O4/pNIPAM/FITC/5-Fu) appear to be a great promise to be used in controlled drug delivery and tumor targeting.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech