Cyclodextrin-scaffolded glycotransporters for gene delivery

Abstract: Conventional drugs consist of a formulation of a bioactive species and a carrier, the former accounting for most of the sophistication of the design. In the case of biomolecular drugs, however, the role of the carrier becomes decisive in enabling the load to reach its target to carry out its designed therapeutic function. Thus, the clinical success of gene therapy, where the active principles are nucleic acids, critically depends on the use of efficient and safe delivery systems. Carbohydrates have proven particularly useful in this regard. Glycocoating, similarly to poly(ethylene)glycol (PEG)-coating (pegylation), can stabilize colloidal aggregates by improving solvation and preventing nonspecific interactions, for example, with serum proteins. Moreover, glycoconjugates can drive specific recognition and receptor-mediated internalization in target cells. Actually, the inherent flexibility of carbohydrate and glycoconjugate chemistry has greatly contributed to enlarging the range of functional materials that can be rationally conceived for gene delivery. Herein, this is illustrated with selected examples that focus on controlling the architectural parameters of the vectors to make them suitable for structure¿activity relationship (SAR) and optimization studies. The members of the cyclomaltooligosaccharide (cyclodextrin, CD) family will be the central actors of the story.Peer Reviewe

Influence of Reynolds number on theoretical models for trailing vortices

We conduct direct numerical simulations for a NACA0012 airfoil at Reynolds numbers (Re) ranging from 300 to 7000 to determine the wake behavior behind this wing profile. We characterize the structure of the wing-tip vortex, finding a reasonable agreement with experimental results at Re=7000. In addition, we model the trailing vortex theoretically, thus obtaining the parameters for Batchelor’s and Moore and Saffman’s models. We compare the results of the best fitting for the axial vorticity and the azimuthal velocity, finding only small discrepancies. The main contribution of this research work is to study the evolution of these theoretical parameters as function of the Reynolds number. We observe that the wake becomes unstable at Re ≈1200, in agreement with previous results. These instabilities in the wake behind the wing produce a change in the trend of theoretical parameters (keywords: vortex dynamics, trailing vortices, theoretical models).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ensembles of Deep Learning Architectures for the Early Diagnosis of the Alzheimer’s Disease.

Computer Aided Diagnosis (CAD) constitutes an important tool for the early diagnosis of Alzheimer’s Disease (AD), which, in turn, allows the application of treatments that can be simpler and more likely to be effective. This paper explores the construction of classification methods based on deep learning architectures applied on brain regions defined by the Automated Anatomical Labeling (AAL). Gray Matter (GM) images from each brain area have been split into 3D patches according to the regions defined by the AAL atlas and these patches are used to train different deep belief networks. An ensemble of deep belief networks is then composed where the final prediction is determined by a voting scheme. Two deep learning based structures and four different voting schemes are implemented and compared, giving as a result a potent classification architecture where discriminative features are computed in an unsupervised fashion. The resulting method has been evaluated using a large dataset from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Classification results assessed by cross-validation prove that the proposed method is not only valid for differentiate between controls (NC) and AD images, but it also provides good performances when tested for the more challenging case of classifying Mild Cognitive Impairment (MCI) Subjects. In particular, the classification architecture provides accuracy values up to 0.90 and AUC of 0.95 for NC/AD classification, 0.84 and AUC of 0.91 for stable MCI/AD classification and 0.83 and AUC of 0.95 for NC/MCI converters classification.This work was partly supported by the MICINN un der the projects TEC2012-34306 and PSI2015-65848- R, and the Consejer´ıa de Innovaci´on, Ciencia y Em presa (Junta de Andaluc´ıa, Spain) under the Ex cellence Projects P09-TIC-4530, P11-TIC-7103 and the Universidad de M´alaga. Programa de fortalec imiento de las capacidades de I+D+I en las Uni versidades 2014-2015, de la Consejer´ıa de Econom´ıa, Innovaci´on, Ciencia y Empleo, cofinanciado por el fondo europeo de desarrollo regional (FEDER) un der the project FC14-SAF30. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Ini tiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bio engineering, and through generous contributions from the following: AbbVie, Alzheimer’s Associa tion; Alzheimer’s Drug Discovery Foundation; Ara clon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; Eu roImmun; F. Hoffmann-La Roche Ltd and its affili ated company Genentech, Inc.; Fujirebio; GE Health care; IXICO Ltd.; Janssen Alzheimer Immunother apy Research & Development, LLC.;Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity ; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Re search is providing funds to support ADNI clinical sites in Canada. Private sector contributions are fa cilitated by the Foundation for the National Insti tutes of Health (www.fnih.org). The grantee organi zation is the Northern California Institute for Re search and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California

A abordagem do direito ao habitat na educação formal da Galicia

El artículo aborda la experiencia de trabajo conjunto dentro del Plan Proxecta entre Arquitectura sen Fronteiras, una Organización No Gubernamental, y el Proxecto Terra, del Colegio Oficial de Arquitectos de Galicia. Se amplía conceptualmente la acción conjunta en los centros educativos a través de la visibilización, reconocimiento, apropiación, transformación y reflexión en torno a las diversas realidades y la vindicación de la “justicia social” mediante el fomento de la acción significativa y participativa del alumnado empleando sus propios saberes y conocimientos. Esta articulación de la mirada socioafectiva significativa y situada forma parte de la transformación real de la realidad del hábitatThe article tries to approach the experience of joint work within the Plan Proxecta entre Arquitectura sen Fronteiras, a non-profit organization, and the Proxecto Terra, of the Official College of Architects of Galicia Their jointly line of action in schools is conceptually broadened through visibility, recognition, appropriation, transformation and reflection around the various realities and vindications of "social justice" through the promotion of significant and participative actions of the students using their knowledge. This articulation of the significant and situated socio-affective gaze is part of the real transformation of habitat’s realityEste artigo aborda a experiência de um trabalho coletivo no âmbito do Plan Proxecta entre Arquitectura sen Fronteiras, uma ONG, eo Proxecto Terra, o Colégio Oficial de Arquitectos da Galiza. Aborda-se conceptualmente a acção conjunta nos centros educativos através do reconhecimento, apropriação, transformação e reflexão sobre as diversas realidades e a reivindicação da “justiça social” através da acção significativa e participativa dos alunos utilizando os seus saberes e conhecimentos. Esta articulação de uma abordagem sócio-afectiva é parte da transformação concreta da realidade do habita

Harmonized tuning of nucleic acid and lectin binding properties with multivalent cyclodextrins for macrophage-selective gene delivery

Polycationic amphiphilic cyclodextrins (paCDs) have been shown to behave as efficient non-viral gene carriers paralleling the efficacy of commercial vectors towards a variety of cell lines. Their molecular framework and modular design allow the installation of saccharidic antennae to promote specific carbohydrate–protein interactions, thus potentially endowing them with selective targeting abilities. Yet, the presence of these additional functionalities onto the polycationic cluster may hamper paCD self-assembly and nucleic acid condensation. In this report we describe the influence of paCD mannosylation extent on paCD-pDNA nanocomplex stability as well as the consequences of varying glycotope density on mannose-specific lectin recognition and gene delivery capabilities. The work aims at exploring the potential of this approach to optimize both properties in order to modulate cell transfection selectivity.Ministerio de Economía y Competitividad SAF2013-44021-RJunta de Andalucía FQM-146

Enhancing Multimodal Patterns in Neuroimaging by Siamese Neural Networks with Self-Attention Mechanism.

The combination of different sources of information is currently one of the most relevant aspects in the diagnostic process of several diseases. In the field of neurological disorders, different imaging modalities providing structural and functional information are frequently available. Those modalities are usually analyzed separately, although a joint of the features extracted from both sources can improve the classification performance of Computer-aided diagnosis (CAD) tools. Previous studies have computed independent models from each individual modality and combined then in a subsequent stage, which is not an optimum solution. In this work, we propose a method based on the principles of siamese neural networks to fuse information from Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). This framework quantifies the similarities between both modalities and relates them with the diagnostic label during the training process. The resulting latent space at the output of this network is then entered into an attention module in order to evaluate the relevance of each brain region and modality at different stages of the development of Alzheimer’s disease. The excellent results obtained and the high flexibility of the method proposed allows fusing more than two modalities, leading to a scalable methodology that can be used in a wide range of contexts.This work was supported by projects PGC2018- 098813-B-C32 and RTI2018-098913-B100 (Spanish “Ministerio de Ciencia, Innovación y Universidades”), UMA20-FEDERJA-086, A-TIC-080- UGR18 and P20 00525 (Consejería de economía y conocimiento, Junta de Andalucía) and by European Regional Development Funds (ERDF); and by Spanish “Ministerio de Universidades” through Margarita-Salas grant to J.E. Arco

La resistencia al cambio durante la implementación de un sistema ERP

The objective of this research was to identify the factors that influence resistance to change by users of automotive agencies during the implementation of an ERP system. It is an in-process documentary and field investigation in situ, with a non-experimental, transactional design. This was a descriptive research with a quantitative and qualitative focusing. In this document, the progress of the quantitative research realized through the application of 35 questionnaires used to obtain data in March 2020 is reported, at the GMC and BMW agencies and the Shared Services Unit. The results showed that the biggest resistance to change manifested was due to factors that make up the dimension called knowledge, reason why it was concluded that it is necessary to evaluate the strategies that help to mitigate misinformation or lack of knowledge when implementing an ERP System.El objetivo de este estudio fue identificar los factores que inciden en la resistencia al cambio por parte de los usuarios de las agencias automotrices durante la implementación de un sistema ERP. Es una investigación en proceso documental y de campo in situ, con diseño no experimental, transeccional. Se trató de un estudio con alcance descriptivo con enfoque cuantitativo y cualitativo. En este documento, se reporta el avance del estudio cuantitativo realizado mediante la aplicación de 35 cuestionarios usados para la obtención de datos en el mes de marzo del 2020, en las agencias GMC y BMW y la Unidad de Servicios Compartidos. Los resultados mostraron que la mayor resistencia al cambio manifestada fue a causa de factores que integran la dimensión denominada conocimiento, por lo que se concluyó que es necesario evaluar las estrategias que ayuden a mitigar la desinformación o falta de conocimiento al implementar un Sistema ERP

Efecto de las estelas en los parques eólicos

Para el diseño de parques eólicos es de interés conocer la producción de energía eléctrica de las turbinas eólicas, o aeroturbinas, así como las cargas que pueden sufrir las mismas limitando su vida útil. La producción de energía está ligada a la intensidad del viento incidente, y la vida útil de las aeroturbinas al grado de agitación turbulenta del viento. El grupo de Mecánica de Fluidos Aplicado a la Ingeniería Industrial de la UPM, ha desarrollado programas informáticos para estimar la magnitud del viento y la intensidad de la turbulencia, en función de las características del terreno y de la distribución de las turbinas en el parque eólico, utilizando para ello modelos numéricos que simulan el movimiento turbulento de los fluidos

Efectos topográficos en el recurso eólico.

Para el diseño de parques eólicos es de interés conocer la producción de energía eléctrica de las turbinas eólicas, o aeroturbinas, así como las cargas que pueden sufrir las mismas limitando su vida útil. La producción de energía está ligada a la intensidad del viento incidente, y la vida útil de las aeroturbinas al grado de agitación turbulenta del viento. El grupo de Mecánica de Fluidos Aplicado a la Ingeniería Industrial de la UPM, ha desarrollado programas informáticos para estimar la magnitud del viento y la intensidad de la turbulencia, en función de las características del terreno y de la distribución de las turbinas en el parque eólico, utilizando para ello modelos numéricos que simulan el movimiento turbulento de los fluido

Melting of crystals of polarization vortices and chiral phase transitions in oxide superlattices

We study the equilibrium arrangements of polarization vortices in (PbTiO3 )n/(SrTiO3 )n superlattices by means of second-principles simulations. We find that, at low temperatures, polarization vortices organize in a regular arrangement in which clockwise and counterclockwise vortices alternate positions, leading to a crystal-like structure with well-defined handedness. This chiral crystal melts at a critical temperature TM into a chiral liquid where long-range order is lost but handedness is preserved. At even higher temperatures TC, a second pase transition occurs at which the chiral liquid of polarization vortices loses its handedness. Both phase transitions can be readily identified by the adequate choices of order parameters.F.G.-O., P.G.-F., and J.J. acknowledge financial support from Grant No. PGC2018-096955-B-C41 funded by MCIN/AEI/10.13039/501100011033 and by ERDF “A way of making Europe,” by the European Union. J.M.L. was funded by Grant No. FIS2016-74957-P MCIN/AEI/10.13039/501100011033/ and ERDF “A way of making Europe” by the European Union. F.G.-O. acknowledges financial support from Grant No. FPU18/04661 funded by MCIN/AEI/10.13039/501100011033. We thankfully acknowledge computing time at Altamira supercomputer and the technical support provided by the Instituto de Física de Cantabria (IFCA) and Universidad de Cantabria (UC). We also thank J. Á. Herrero for his valuable assistance with the supercomputing environment HPC/HTC cluster Calderon, supported by datacenter 3Mares from Universidad de Cantabri