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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Automotive Lighting Systems Based on Luminance/Intensity Grids: A Proposal Based on Real-Time Monitoring and Control for Safer Driving

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Computers, Materials & Continua 2021年第3期66卷 2373-2383页

作者： antonio Peña-garcía Huchang Liao Department of Civil Engineering&Research Group“Lighting Technology for Safety and Sustainability” University of GranadaGranada18071Spain Business School Sichuan UniversityChengdu610064China

The requirements for automotive lighting systems,especially the light patterns ensuring driver perception,are based on criteria related to the headlamps,rather than the light perceived by drivers and road ***,important factors such as pavement reflectance,driver age,or time of night,are largely *** factors such as presence of other vehicles,vehicle speed and weather conditions are considered by the Adaptive Driving Beam(ADB)and Adaptive Front-lighting System(AFS)respectively,though with no information regarding the visual perception of drivers and other road ***,it is simpler to simulate and measure the light emitted by the lamps than the light reflected by the pavement or emitted by other *** the current technology in cameras and light sensors,communication protocols,and control of Light Emitting Diodes(LED),combined with decision-making techniques applied to large amounts of data,can open a new era in the operation of headlamps and thus ensure the visual needs of drivers in real time and under actual road *** solution lies in an interaction road-sensor-headlamp,which is not based on the light emitted by headlamps,but rather on the light perceived by the *** study thus proposes a dual grid based on luminance and luminous intensity,which would manage the headlamps by optimizing driver perception and the safety of all road users.

关键词： Vehicle systems optical sensing LED control automotive lighting

Comparing Fine-Tuning, Zero and Few-Shot Strategies with Large Language Models in Hate Speech Detection in English

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Computer Modeling in Engineering & Sciences 2024年第9期140卷 2849-2868页

作者： Ronghao Pan Joséantonio garcía-Díaz Rafael Valencia-garcía Departamento de Informática y Sistemas Universidad de MurciaCampus de EspinardoMurcia30100Spain

Large Language Models(LLMs)are increasingly demonstrating their ability to understand natural language and solve complex tasks,especially through text *** of the relevant capabilities is contextual learning,which involves the ability to receive instructions in natural language or task demonstrations to generate expected outputs for test instances without the need for additional training or gradient *** recent years,the popularity of social networking has provided a medium through which some users can engage in offensive and harmful online *** this study,we investigate the ability of different LLMs,ranging from zero-shot and few-shot learning to *** experiments show that LLMs can identify sexist and hateful online texts using zero-shot and few-shot approaches through information ***,it is found that the encoder-decoder model called Zephyr achieves the best results with the fine-tuning approach,scoring 86.811%on the Explainable Detection of Online Sexism(EDOS)test-set and 57.453%on the Multilingual Detection of Hate Speech Against Immigrants and Women in Twitter(HatEval)***,it is confirmed that the evaluated models perform well in hate text detection,as they beat the best result in the HatEval task *** error analysis shows that contextual learning had difficulty distinguishing between types of hate speech and figurative ***,the fine-tuned approach tends to produce many false positives.

关键词： Hate speech detection zero-shot few-shot fine-tuning natural language processing

Non-coding RNAs and other determinants of neuroinflammation and endothelial dysfunction:regulation of gene expression in the acute phase of ischemic stroke and possible therapeutic applications

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Neural Regeneration Research 2021年第11期16卷 2154-2158页

作者： mario Daidone Marco Cataldi antonio Pinto Antonino Tuttolomondo Department of Health Promotion Maternal and Infant CareInternal Medicine and Medical Specialties“G.D’Alessandro”University of PalermoPiazza delle Cliniche n.2PalermoItaly

Ischemic stroke occurs under a variety of clinical conditions and has different pathogeneses,resulting in necrosis of brain *** pathogenesis is characterized by neuroinflammation and endothelial *** of the main processes triggered in the early stages of ischemic damage are the rapid activation of resident inflammatory cells(microglia,astrocytes and endothelial cells),inflammatory cytokines,and translocation of intercellular nuclear *** in stroke includes all the processes mentioned above,and it consists of either protective or detrimental effects concerning the“polarization”of these *** polarization comes out from the interaction of all the molecular pathways that regulate genome expression:the epigenetic *** recent years,new regulation mechanisms have been cleared,and these include non-coding RNAs,adenosine receptors,and the activity of mesenchymal stem/stromal cells and *** reviewed how long non-coding RNA and microRNA have emerged as an essential mediator of some neurological *** also clarified that their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic *** date,we do not have adequate tools to control pathophysiological processes associated with *** goal is to review the role of non-coding RNAs and innate immune cells(such as microglia and mesenchymal stem/stromal cells)and the possible therapeutic effects of their modulation in patients with acute ischemic stroke.A better understanding of the mechanisms that influence the“polarization”of the inflammatory response after the acute event seems to be the way to change the natural history of the disease.

关键词： acute phase cerebrovascular disease endothelial dysfunction epigenetics genetics neuroiflammation non-coding RNAs stroke

An update on iron physiology

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World Journal of Gastroenterology 2009年第37期15卷 4617-4626页

作者： Manuel Muoz Isabel Villar José antonio garcía-Erce Transfusion Medicine School of Medicine University of Málaga Málaga 29071 Spain Department of Hospital Pharmacy University Hospital Miguel Servet Zaragoza 50009 Spain Hematology and Hemotherapy University Hospital Miguel Servet Zaragoza 50009 Spain

Iron is an essential micronutrient, as it is required for adequate erythropoietic function, oxidative metabolism and cellular immune responses. Although the absorption of dietary iron (1-2 mg/d) is regulated tightly, it is just balanced with losses. Therefore, internal turnover of iron is essential to meet the requirements for erythropoiesis (20-30 mg/d). Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron-deficiency anemia. Hepcidin, which is made primarily in hepatocytes in response to liver iron levels, inflammation, hypoxia and anemia, is the main iron regulatory hormone. Once secreted into the circulation, hepcidin binds ferroportin on enterocytes and macrophages, which triggers its internalization and lysosomal degradation. Thus, in chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, which results in hypoferremia and iron-restricted erythropoiesis, despite normal iron stores (functional ID), and anemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD + ID). In contrast, low hepcidin expression may lead to iron overload, and vice versa. Laboratory tests provide evidence of iron depletion in the body, or reflect iron-deficient red cell production. The appropriate combination of these laboratory tests help to establish a correct diagnosis of ID status and anemia.

关键词： Iron metabolism Iron deficiency Functionaliron deficiency, Hepcidin Anemia of chronic disease

Oligodendroctyes:the forgotten players of diabetes pathophysiology

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Neural Regeneration Research 2024年第11期19卷 2349-2350页

作者： Juan antonio López-Villodres Beatriz garcía-Díaz Departamento Fisiología Humana Histología HumanaAnatomía Patológica y Educación Física y DeportivaFacultad de MedicinaUniversidad de MálagaMálagaSpain UGC Neurociencia.Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma Bionand) MálagaSpain

Oligodendrocytes(OLs),glial cells that provide myelin sheaths to axons in the central nervous system(CNS),have a dual ***,this myelin fatty cover around the axons protects the nerves and is crucial for the saltatory propagation of action *** and not less important,OLs provide trophic support to neurons and ***,OL metabolism is important for OL well-being and the proper accomplishment of their functions,and OL metabolism energetics directly affect the energy metabolism of neighboring neurons.

关键词： metabolism nerves myelin

Effect of Zn binding to phytate and humic substances on its uptake by wheat(Triticum durum L.)as affected by carbonates and Fe oxides

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Pedosphere 2022年第6期32卷 823-832页

作者： Ana M.garcÍA-LÓPEZ Ramiro RECENA antonio DELGADO Department of Agronomy ETSIAUniversity of SevilleSeville 41013(Spain)

Although complexation with soil organic matter may improve zinc(Zn)bioavailability to plants,the effect of Zn sorbent surface on the use of complexed Zn by plants remains *** objective of this research was to elucidate how Zn complexation with humic substances(HS)and phytate affects the uptake of Zn by wheat plants depending on the main sorbent surface in growth media,i.e.,carbonates and Fe *** this end,two pot experiments were performed,one using Fe oxide-coated siliceous as the siliceous growth medium sand and the other using a mixture of calcareous sand and siliceous sand as the calcareous growth *** experiment involved three Zn sources,Zn-HS complex,Zn phytate,and ZnSO_(4).All sources were applied with surface irrigation at two Zn rates(0.25 and 2 mg kg^(-1) growth medium).The Zn-HS complex significantly increased Zn uptake by plants in both media,relative to the other two Zn sources,but no significant difference was observed between Zn phytate and ZnSO_(4).In the calcareous medium,Zn-HS complex and Zn phytate resulted in significantly higher dry biomass yields of wheat than ZnSO_(4).In the siliceous medium,spike and shoot dry biomass yields with Zn-HS complex at the low rate and Zn phytate at both rates were not significantly different from those with ZnSO_(4) at the high *** harvest,approximately 50%of the Zn applied as Zn-HS complex remained extractable by diethylenetriaminepentaacetic acid(DTPA),while this proportion was less than 20%for the other Zn ***,Zn-HS complex and Zn phytate are sources of available Zn for plants,and they are more effective than ZnSO_(4) in increasing plant growth,particularly when carbonates are the main Zn sorbent surface.

关键词： calcareous growth medium micronutrient organic matter organic phosphorus Zn availability Zn deficiency Zn sorbent surface Zn source

Influence of parameters on the microstructure of a duplex stainless steel joint welded by a GMAW welding process

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Progress in Natural Science:Materials International 2022年第4期32卷 415-423页

作者： Sandra Chacón-Fernández antonio Portolés garcía Gerardo Romaní Labanda Universidad Politécnica de Madrid Escuela Técnica Superior de Ingenieros Industriales UPM

Duplex stainless steels（DSSs） are widely used in industry for their desirable properties. Any fusion welding technique modifies the microstructure and, consequently, the properties of the material. This paper presents a parametric study of the variables that determine the energy contribution（current, voltage and welding speed） and the structural modifications produced during gas metal arc welding. The analysis comprises metallographic study,phase balance, dimensioning of the weld beads and tensile and hardness tests. The influence of the variables studied on the thermal cycles obtained（temperatures reached and cooling rate） was determined by using a finite element model. The results showed that, in addition to the indicated parameters, the parameter power transfer per volume（W/m3） and the geometry in the bead must be controlled due to their influence on the heat flow distribution and phase balance.

关键词： Welding Heat input GMAW Duplex stainless steels (DSS) Finite element model (FEM)

Elastic Smart Contracts in Blockchains

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IEEE/CAA Journal of Automatica Sinica 2021年第12期8卷 1901-1912页

作者： Schahram Dustdar Pablo Fernández JoséMaría garcía antonio Ruiz-Cortés Distributed Systems Group Vienna University of TechnologyWien 1040Austria Smart Computer Systems Research and Engineering Lab Research Institute of Computer EngineeringUniversity of SevillaSevilla 41012Spain

In this paper,we deal with questions related to blockchains in complex Internet of Things(IoT)-based *** ecosystems are typically composed of IoT devices,edge devices,cloud computing software services,as well as people,who are decision makers in scenarios such as smart *** decisions related to analytics can be based on data coming from IoT sensors,software services,and ***,they are typically based on different levels of abstraction and *** poses a number of challenges when multiple blockchains are used together with smart *** work proposes to apply our concept of elasticity to smart contracts and thereby enabling analytics in and between multiple blockchains in the context of *** propose a reference architecture for Elastic Smart Contracts and evaluate the approach in a smart city scenario,discussing the benefits in terms of performance and self-adaptability of our solution.

关键词： Blockchain elasticity Internet of Things(IoT) smart cities smart contracts virtual chains