Comparing community detection algorithms in graphs

[Abstract] The detection of communities in graphs has been a very discussed topic in recent years due to the raise of social networks. This topic is not a simple one, and as such, many different solutions have been proposed over the years to try and find communities in these networks. In this project we compare the results of different community detection algorithms when applied to a real live graph. This comparison is made using a set of quality metrics that will give us information of the algorithm’s performance. With this information at hand we have seen that these algorithms perform very differently from each other and that the graph to which they are applied is a very important part in the results they return.[Resumo] A detección de comunidades en grafos foi un tema moi discutido nos últimos anos debido ao auxe das redes sociais. Este tema de estudo non é sinxelo, e por iso propuxéronse moitas solucións diferentes ao longo dos anos para tratar de atopar comunidades nestas redes. Neste proxecto comparamos os resultados de diferentes algoritmos de detección de cando se aplican a un grafo real. Esta comparación realízase empregando un conxunto de métricas de calidade que nos darán información do rendemento dos algoritmos. Coa informacion obtida, vimos que estes algoritmos teñen un comportamento moi distinto entre si e que o grafo ao que se aplican é unha parte moi importante nos resultados que devolven.Traballo fin de grao. Enxeñaría Informática. Curso 2021/202

Los contenidos musicales en la radio digital. Hacia la regulación del espacio digital y los drechos de propiedad intelectual

Esta comunicación aborda la transformación del negocio de la música tras el advenimiento de la era digital. El trabajo analiza el tratamiento de los contenidos musicales en los medios, la imagen de la actividad comercial y musical entre la audiencia y los periodistas especializados, las consecuencias laborales y éticas que ha generado la piratería y las ventajas e inconvenientes que ha reportado el cambio digital en la promoción de la música. Finalmente se ofrecen alternativas de explicación a los debates y contradicciones sobre la regulación y gestión de los derechos de propiedad intelectual que promueven distintos sectores con intereses enfrentados.This communication provides an overview of the music business and its gradual transformation from the advent of the digital age. Furthermore, an analysis of treatment of musical content in the media, the image that the music business and is set on the audience and journalists, labour and ethical implications of consumer piracy has generated. Finally, we offer various alternative explanations for the debates and contradictions about regulation and management of intellectual property rights promoted from different sectors, each with conflicting interests

Hydrazone-modulated peptides for efficient gene transfection

Gene transfection continues to be a major challenge in chemistry, biology and materials sciences. New methodologies and recent breakthroughs have renewed the interest in the discovery and development of new tools for efficient gene transfection. Hydrazone formation between a cationic head and hydrophobic tails has emerged as one of the most promising techniques for nucleotide delivery. In this contribution, we have exploited hydrazone formation to modulate the transfection activity of a parent linear peptide in combination with a plasmid DNA cargo. This strategy allowed the straightforward preparation, under physiologically compatible conditions, of a discrete library of amphiphilic modulated penetrating peptides. Without the requirement of any isolation or purification steps, these modulated amphiphilic peptides were combined with a plasmid DNA and screened in transfection experiments of human HeLa cells. Three of these hydrazone-conjugated peptides were identified as excellent vectors for plasmid delivery with comparable, or even higher, efficiencies and lower toxicity than the commercial reagents employed in routine transfection assaysWe are thankful to Dr. Irene Lostalé-Seijo for cell culture assistance and discussions. We acknowledge funding from the Spanish Government MINECO: [CTQ2014-59646-R] and [CTQ2015-74621-JIN], the Xunta de Galicia (ED431G/09), the ERDF and the CESGA. R. G.-F. received a FCT Investigator Grant from Portugal (IF/01133/2015). J.M. received a Ramon y Cajal (RYC-2013-13784) and an ERC Starting Investigator Grant (DYNAP-677786)S

Reacciones de formación de sistemas policíclicos: I. Síntesis de taxoesteroides mediante metátesis de dieninos. II. Estudios teóricos de reacciones de ciclación de metátesis y reacciones de cicloadición [3+2] catalizadas por Pd

Polycyclic systems containing medium size rings are present in a high number of compounds and constitute the basic skeleton of natural and non natural products of great importance. The construction of these systems continues being a challenge in the Synthetic Organic Chemistry. Transition metals have become ideal candidates for their synthesis, because of their multiple advantages: all functional groups can coordinate to some transition metals, and after that, the reactivity of this functional group is incredibly changed very often. Besides, most of the reactions can be carried out in a very specifically way, and it is possible to distinguish between similar positions into the same molecule. Another advantage is that transition metals can participate in domino or tandem reactions, where more than one bond can be formed at the same time. However, the mechanisms of these transformations are often complicated and difficult to understand. This fact, more than a disadvantage can be considered a great chance for the development of new chemical transformations. This memory describes the results obtained from the investigation of two important reactions catalyzed by a transition metal: metathesis and cycloaddition reactions. Both transformations constitute big synthetic tools and allow achieving a big molecular complexity in only one step; this is why they are so useful in the construction of polycyclic systems

Palladium-Catalyzed Conjugate Addition of Terminal Alkynes to Enones

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: https://pubs.acs.org/doi/10.1021/ol300988nA practical protocol for the hydroalkynylation of enones using Pd catalysis is reported. The reaction proceeds efficiently with a variety of alkynes as well as with several cyclic and acyclic enones, providing synthetically relevant β-alkynyl ketones in good to excellent yieldsThis work was supported by the Spanish MINECO [SAF2007-61015, SAF2010-20822-C02, Consolider Ingenio 2010 CSD2007-00006], the ERDF and the Xunta de Galicia INCITE09209084PR, GRC2010/12. L.V. and R.G.-F. thank the Spanish MEC and MINECO for an FPU fellowship and a Juan de la Cierva contract, respectivelyS

Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir

The formation of small hybrid aggregates between excipient and drug molecules is one of the mechanisms that contributes to the solubilization of active principles in pharmaceutical formulations. The characterization of the formation, governing interactions and structure of such entities is not trivial since they are highly flexible and dynamic, quickly exchanging molecules from one to another. In the case of cyclodextrins, this mechanism and the formation of inclusion complexes synergistically cooperate to favour the bioavailability of drugs. In a previous study we reported a detailed characterization of the possible formation of inclusion complexes with 1:1 stoichiometry between remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, and sulphobutylether-β-cyclodextrins. Here we extend our study to assess the role of the spontaneous aggregation in the solubilization of the same drug, by molecular dynamics simulations at different relative concentrations of both compounds. The number of sulphobutylether substitutions in the cyclodextrin structure and two different protonation states of the remdesivir molecule are considered. We aim to shed light in the solubilization mechanism of sulphobutylether-β-cyclodextrins, broadly used as an excipient in many pharmaceutical formulations, in particular in the case of remdesivir as an active compoundR.G.-F thanks to the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (RTI2018-098795-A-I00) and for a “Ramón y Cajal” contract (RYC-2016-20335), to Xunta de Galicia (ED431F 2020/05) and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03) and the European Union (European Regional Development Fund - ERDF). Á. P. thanks to the Ministerio de Ciencia e Innovación (PID2019-111327 GB-I00)S

Remdesivir interactions with sulphobutylether-β-cyclodextrins: a case study using selected substitution patterns

Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be effectively used. The most typical interaction mechanism of small molecular groups with CDs is the formation of host–guest inclusion complexes. The thermodynamic affinity constant between CDs and drugs should not be too strong, since then the biological activity could be negated by the formation of the complex. In the opposite scenario, if the affinity constant is too weak, the complex is barely formed and the amount of CD required in the formulation may become too great. Thus, a balance between the affinity of the CD and the drug is necessary for an optimal formulation. Additionally in the case of modified CDs and specific drug complexes there are further questions concerning the effect that the locations and number of substitutions plays in complexation. In the present work, this question is explored by using sulphobutylether-β-cyclodextrin and remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, as a case study. This paper presents results from an orthogonal study using isothermal titration calorimetry measurements and biased molecular dynamics simulations that provide complementary information. Isothermal titration calorimetry delves into the global impact of the species distribution while molecular dynamics simulations deals with specific chemical structures. The goal is to provide useful information to optimize pharmaceutical formulations based on modified CDs, specifically in the case of remdesivir, used to treat SARS-CoV-2 infection, although the main conclusions could be extended to the interaction of other drugs with modified cyclodextrinsR.G.-F thanks to the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (RTI2018-098795-A-I00) and for a “Ramón y Cajal” contract (RYC-2016-20335), to Xunta de Galicia (ED431F 2020/05) and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03) and the European Union (European Regional Development Fund - ERDF). Á. P. thanks to the Ministerio de Ciencia e Innovación (PID2019-111327GB-I00). We thank the “Centro de Supercómputo de Galicia” (CESGA) for computing time as well as for their exceptional technical supportS

Molecular insights into the effects of focused ultrasound mechanotherapy on lipid bilayers:Unlocking the keys to design effective treatments

Administration of focused ultrasounds (US) represents an attractive complement to classical therapies for a wide range of maladies, from cancer to neurological pathologies, as they are non-invasive, easily targeted, their dosage is easy to control, and they involve low risks. Different mechanisms have been proposed for their activity but the direct effect of their interaction with cell membranes is not well understood at the molecular level. This is in part due to the difficulty of designing experiments able to probe the required spatio-temporal resolutions. Here we use Molecular Dynamics (MD) simulations at two resolution levels and machine learning (ML) classification tools to shed light on the effects that focused US mechanotherapy methods have over a range of lipid bilayers. Our results indicate that the dynamic-structural response of the membrane models to the mechanical perturbations caused by the sound waves strongly depends on the lipid composition. The analyses performed on the MD trajectories contribute to a better understanding of the behavior of lipid membranes, and to open up a path for the rational design of new therapies for the long list of diseases characterized by specific lipid profiles of pathological membrane cells.</p

Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes

The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulationsThis work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (RTI2018-098795-A-I00), and by the Xunta de Galicia and the ERDF (ED431C 2017/25 and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09). P.F.G. is funded by a predoctoral research grant (BES-2016-076761) from the Spanish Ministry of Economy and Competitiveness and the European Social Fund. M.C. is funded by a predoctoral fellowship from Xunta de Galicia. R.G.-F. is a “Ramón y Cajal” fellowship (RYC-2016-20335) from the Ministerio de Ciencia, Innovación y UniversidadesS