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Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease

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Translational Neurodegeneration 2023年第1期12卷 801-823页

作者： luis Enrique Arroyo-García Sara Bachiller Rocío Ruiz antonio Boza-Serrano antonio Rodríguez-Moreno Tomas Deierborg Yuniesky Andrade-Talavera AndréFisahn Neuronal oscillations Laboratory Division of NeurogeriatricsCenter for Alzheimer ResearchDepartment of NeurobiologyCare Sciences and SocietyKarolinska Institutet17164 SolnaSweden Experimental Neuroinflammation Laboratory Department of Experimental Medical ScienceLund UniversityBMC B1122184 LundSweden Clinical Unit of Infectious Diseases Microbiology and ParasitologyInstitute of Biomedicine of Seville(IBiS)Virgen del Rocío University HospitalCSICUniversity of SevilleSevilleSpain Department of Biochemistry and Molecular Biology University of SevilleCalle Profesor García González Nº241012 SevilleSpain Laboratory of Cellular Neuroscience and Plasticity Department of PhysiologyAnatomy and Cellular BiologyUniversidad Pablo de OlavideCarretera de Utrera Km-141013 SevilleSpain Department of Biosciences and Nutrition NeoKarolinska Institutet14183 HuddingeSweden

Background Alzheimer’s disease(AD)is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment *** is central to the pathology progression,with evidence suggesting that microglia-released galectin-3(gal3)plays a pivotal role by amplifying neuroinflammation in ***,the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains *** Here,we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo(20-80 Hz)by performing electrophysiological recordings in the hippocampal CA3 area of wild-type(WT)mice and of the 5×FAD mouse model of *** addition,the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes,and amyloid-β(Aβ)plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout(Ko).Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner,which was accompanied by impairment of cellular dynamics in fast-spiking interneurons(FSNs)and pyramidal *** found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139,which also prevented Aβ42-induced degradation of gamma ***-more,the 5×FAD mice lacking gal3(5×FAD-Gal3Ko)exhibited WT-like gamma network dynamics and decreased Aβplaque *** We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs,inducing a network performance ***,our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

关键词： Galectin-3 Gamma oscillations Neuronal network dynamics Fast-spiking interneurons Alzheimer’s disease models Neuroinflammation TD139 Hippocampus

A methodology for assessing the urban supply of on-street delivery bays

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Green Energy and Intelligent Transportation 2022年第3期1卷 63-72页

作者： antonio Comi Joséluis Moura Sara Ezquerro University of Rome Tor Vergata RomeItaly University of Cantabria SantanderSpain

The loading and unloading operations carried out by transport and logistics operators have a strong impact on city mobility if they are not performed *** loading/unloading bays,i.e.,delivery bays(DB),are not available for freight vehicle operations,operators may opt to double park or park on the sidewalk where there is no strong enforcement of these laws,with significant impact on *** paper proposes a methodology for verifying and designing the number of delivery bays needed for freight vehicles for not interfere with cars or *** methodology consists of two stages:in the first stage,an initial estimation is made using queueing ***,in the second stage,using such tentative scenario,in order to take into account the system stochasticity involving different entities,a discrete event simulation is performed to more realistically verify and upgrade(if necessary)the number of delivery bays to obtain the expected *** methodology was applied in the inner area of Santander(Spain).The study area was subdivided into 29 zones where the methodology was applied *** results indicated that none of these zones currently have an optimal number of delivery bays to satisfy *** some zones,there is an excess of delivery bays,although in most of them,there is a deficit which can cause significant impacts on *** method proposed can be an effective tool to be used by city planners for improving freight operations in urban areas limiting the negative impacts produced in terms of internal and external costs.

关键词： Urban freight transportation on-street delivery bays Discrete event simulation City logistics Urban goods movements

Computational design in architecture:Defining parametric,generative,and algorithmic design

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Frontiers of Architectural Research 2020年第2期9卷 287-300页

作者： Ines Caetano luis Santos antonio Leitao INESC-ID/Instituto Superior Tecnico University of LisbonLisbonPortugal College of Architecture and Environmental Design Kent State UniversityKentUSA

Computation-based approaches in design have emerged in the last decades and rapidly became popular among architects and other *** professionals and researchers adopted different terminologies to address these ***,some terms are used ambiguously and inconsistently,and different terms are commonly used to express the same *** paper discusses computational design(CD)and proposes an improved and sound taxonomy for a set of key CD terms,namely,parametric,generative,and algorithmic design,based on an extensive literature review from which different definitions by various authors were collected,analyzed,and compared.

关键词： Algorithmic design Computer-aided design Computational design Generative design Parametric design

TinyML-Based Fall Detection for Connected Personal Mobility Vehicles

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Computers, Materials & Continua 2022年第5期71卷 3869-3885页

作者： Ramon Sanchez-Iborra luis Bernal-Escobedo Jose Santa antonio Skarmeta University Center of Defense General Air Force AcademySan Javier30720Spain University of Murcia Murcia30100Spain Technical University of Cartagena Cartagena30202Spain

A new wave of electric vehicles for personal mobility is currently crowding public *** offer a sustainable and efficient way of getting around in urban environments,however,these devices bring additional safety issues,including serious accidents for ***,taking advantage of a connected personal mobility vehicle,we present a novel on-device Machine Learning(ML)-based fall detection system that analyzes data captured from a range of sensors integrated on an on-board unit(oBU)*** the typical processing limitations of these elements,we exploit the potential of the TinyML paradigm,which enables embedding powerful ML algorithms in constrained *** have generated and publicly released a large dataset,including real riding measurements and realistically simulated falling events,which has been employed to produce different TinyML *** attained results show the good operation of the system to detect falls efficiently using embedded *** considered algorithms have been successfully tested on mass-market low-power units,implying reduced energy consumption,flash footprints and running times,enabling new possibilities for this kind of vehicles.

关键词： Personal mobility machine learning on-board unit C-ITS IoT

Attosecond twisted beams from high-order harmonicgeneration driven by optical vortices

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High Power Laser Science and Engineering 2017年第1期5卷 12-19页

作者： Carlos Hernandez-Garcia Laura Rego Julio San Roman antonio Picon luis Plaja Grupo de Investigacion en Aplicaciones del Laser y Fotonica Departamento de Fisica AplicadaUniversity of SalamancaE-37008SalamancaSpain Argonne National Laboratory Argonne1L 60439USA

optical vortices are structures of the electromagnetic field with a spiral phase ramp about a point-phase singularity,carrying orbital angular momentum(oAM). Recently, oAM has been imprinted to short-wavelength radiation through high-order harmonic generation(HHG), leading to the emission of attosecond twisted beams in the extreme-ultraviolet(XUV) regime. We explore the details of the mapping of the driving vortex to its harmonic spectrum. In particular, we show that the geometry of the harmonic vortices is convoluted, arising from the superposition of the contribution from the short and long quantum paths responsible of HHG. Finally, we show how to take advantage of transverse phase-matching to select twisted attosecond beams with different spatiotemporal properties.

关键词： attosecond science extreme-ultraviolet vortices high harmonic generation orbital angular momentum twisted beams vortexbeams

Apomorphine effects on the hippocampus

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Neural Regeneration Research 2018年第12期13卷 2064-2066页

作者： luis Enrique Arroyo-García antonio Rodríguez-Moreno Gonzalo Flores Laboratorio de Neuropsiquiatria Instituto de Fisiologia Benemerita Universidad Autenoma de Puebla Puebla Mexico Laboratorio de Neurociencia Celular y Plasticidad Universidad Pablo de Olavide Sevilla Spain

Apomorphine is a non-specific dopamine receptor agonist that has been used in the treatment of some diseases and mental disorders. Its use has particularly well documented in Parkinson＇s disease（PD）. The dopaminergic agonists like apomorphine are related to oxidative processes that could induce cell damage and the functional impairment of some structures in the brain. However, most information about apomorphine in literature is focused on the improvement of the motor problems characteristic of PD, but little is known about the effects on cognitive behaviors and brain structures indirectly related to motor function. The presence of dopaminergic receptors in the hippocampus has recently been discovered, in connection with cognitive behaviors like learning and memory, these receptors are needed in neuronal plasticity. There has been a growing interest to know if this structure could be compromised by the effect of apomorphine and elucidate if part of the cognitive impairment present in the PD is due to the effect of apomorphine. In this mini-review, we summarized how apomorphine has been used since its creation, we discuss the latest information about its effect on the hippocampus and also the future perspectives to fully understand the effects of this compound.

关键词： dopamine receptor apomorphine hippocampus learning and memory plasticity dendritic length oxidative stress Parkinson's disease

The Role of the Solar Cycle in the Relationship Between the North Atlantic oscillation and Northern Hemisphere Surface Temperatures

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Advances in Atmospheric Sciences 2007年第2期24卷 191-198页

作者： Laura DE LA ToRRE luis GIMENo Juan antonio AEL Raquel NIETo Universidad de Vigo Facultad de Ciencias de ourense 32004OurenseSpain

The North Atlantic oscillation （NAo） is one of the leading modes of climate variability in the Northern Hemisphere. It has been shown that it clearly relates to changes in meteorological variables, such as surface temperature, at hemispherical scales. However, recent studies have revealed that the NAo spatial pattern also depends upon solar forcing. Therefore, its effects on meteorological variables must vary depending upon this factor. Moreover, it could be that the Sun affects climate through variability patterns, a hypothesis that is the focus of this study. We find that the relationship between the NAo/Ao and hemispheric temperature varies depending upon solar activity. The results show a positive significant correlation only when solar activity is high. Also, the results support the idea that solar activity influences tropospheric climate fluctuations in the Northern Hemisphere via the fluctuations of the stratospheric polar vortex .

关键词： solar activity North Atlantic oscillation Arctic oscillation Northern Hemisphere surface temperature

Pharmacological treatments of presbyopia:a review of modern perspectives

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Eye and Vision 2017年第1期4卷 14-17页

作者： antonio Renna Jorge L.Alió luis Felipe Vejarano Vissum Alicante AlicanteSpain Studi Medici Renna MelendugnoLecceItaly Universidad Miguel Hernandez Calle Cabañal 103016 AlicanteSpain Vissum Instituto oftalmologico de Alicante AlicanteSpain Fundación oftalmológica Vejarano PopayanColombia Universidad del Cauca PopayanColombia

Introduction:Presbyopia affects people from the 4^(th) decade of life and is characterized by accommodative loss that leads to negative effects on vision-targeted health-related quality of life.A non-invasive pharmacological treatment providing near-lenses independence would be a truly groundbreaking approach in the treatment of *** purpose of this review is to analyze the emerging pharmacological solutions proposed to address ***:Several ophthalmic eye drops compounds solutions have been described in peer-reviewed papers or presented in ophthalmological tabloids and *** topical treatment deals with drug combinations aimed to modify one or more factors involved in the accommodative process and have been proposed to be instilled either monocularly or *** remains unclear how much each drug in the final combined form is involved in the achievement of the outcome and contributes to ***:Despite the lack of a completely well understood mechanism,pharmacological control of presbyopia seems to be a possible and very attractive alternative for presbyopic *** studies mentioned in this review are to be considered pilot investigations as they involve either a small number of subjects or are single case *** studies are needed to confirm which will be the more effective pharmacological compound for the treatment of presbyopia.

关键词： Presbyopia Ageing Near vision Glasses Multifocality Accommodation Pharmacological therapy Eyedrops

Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

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Journal of Pharmaceutical Analysis 2016年第2期6卷 117-124页

作者： antonio Martinez-ortega Agustin Herrera antonio Salmeron-Garcia Jose Cabeza luis Cuadros-Rodriguez Natalia Navas Department of Analytical Chemistry University of Granada Faculty of Science Campus Fuentenueva s/n E-18071 Granada Spain UGC intercentro Interniveles Farmacia Granada San Cecilio Hospital Biomedical Research Institute ibs. GRANADA. Hospitales Universitarios de Granada University of Granada E-18012 Granada Spain Department of Analytical Chemistry Science Faculty Biomedical Research Institute ibis. GRANADA University of Granada Campus Fuentenuevo s/n E-18071 Granada Spain

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

关键词： Reverse-phase high performance liquidchromatography Diode detector Stress study Biopharmaceuticals Cetuximab