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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

Stability analysis of the fluttering and autorotation of flow-induced rotation of a hinged flat plate

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Journal of Hydrodynamics 2013年第5期25卷 755-762页

作者： MIRZAEISEFAT Sina FERNANDES antonio carlos Department of Naval Architecture and marine Engineering University of Michigan COPPE/UFRJ Federal University of Rio de Janeiro

This work describes investigations performed on the interaction of uniform current and freely rotating plate about a fixed vertical axis. Fluttering and autorotation are two different motions that may occur during the flow induced rotation. The dimensional analysis proves that the motion in flow induced rotation motion is governed essentially by the dimensionless moment of inertia and Reynolds number. Certain combinations define the stability boundaries between fluttering and autorotation. Fluttering is oscillation of body about a vertical axis and the autorotation is a name given to the case when the body turns continuously about the vertical axis First, the loads and moment coefficients are calculated by experiments and streamline theory for different angles of attack for a fixed fiat plate. Then for dynamic case, a bifurcation diagram is presented based on experiments to classify different motion states of flow induced rotation. Finally, a dynamical model is proposed for stability analysis of flow induced rotation of a flat plate.

关键词： flow-induced rotation autorotation fluttering stability analysis

Phenomenological model for torsional galloping of an elastic flat plate due to hydrodynamic loads

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Journal of Hydrodynamics 2014年第1期26卷 57-65页

作者： FERNANDES antonio carlos ARMANDEI Mohammadmehdi Department of Naval and Ocean Engineering COPPE/UFRJ

This study investigates the torsional galloping phenomenon, an instability type flow-induced oscillation, in an elastic stru-cture due to hydrodynamic loads into the water current. The structure applied here is a rectangular flat plate with an elastic axis in its mid-chord length. The elasticity is provided by torsion spring. The flat plate has only one degree of freedom which is rotation in pure yaw about its axis. It is observed that as the current speed is higher than a critical velocity, the flat plate becomes unstable. The instability leads to torsional galloping occurrence, as a result of which the flat plate begins to yaw about the elastic axis. By testing two different chord lengths each with several torsion spring rates, the flat plate behavior is investigated and three different responses are recognized. Then, a phenomenological model is developed with the original kernel in the form of the van der Pol-Duffing equa-tion. The model explains these three responses observed experimentally.

关键词： torsional galloping flow-induced oscillation phenomenological model van der Pol-Duffing equation

Impact of radiative cooling on the energy performance of courtyards in Mediterranean climate

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Building Simulation 2024年第9期17卷 1491-1513页

作者： carlos-antonio Domínguez-Torres antonio Domínguez-Delgado Escuela Técnica Superior de Arquitectura Universidad de SevillaAv.de Reina Mercedes241012 SevillaSpain Department of Applied Mathematics 1 Escuela Técnica Superior de ArquitecturaUniversidad de SevillaAv.de Reina Mercedes241012 SevillaSpain

Radiative cooling has proven to be a useful tool to address the problems of lack of comfort and excessive energy consumption in situations of high temperatures,overheating and heat ***,incorporating courtyards in warm climate zones has been found to be highly beneficial in addressing similar ***,there is interest in analyzing the combined effects of both:radiative cooling and *** paper presents an analysis of the impact of the application of radiative cooling on a courtyard using a comprehensive simulation approach that includes a CFD model for the thermodynamic airflow in the adjacent roofs and inside the courtyard,equations for the transient heat conduction through roofs,walls and courtyard slabs,and a hybrid raytracing-radiosity model for the evaluation of the solar radiation reaching the building surfaces and its reflections,both of specular and diffuse origin,and for the calculation of the thermal radiation exchange,especially with the *** results show that in the hot season,the courtyard with radiative cooling always provides lower temperatures than the initial courtyard does,with a temperature range of 18.33℃to 33.78℃,compared to a range of 19.32℃to 38.00℃in the initial courtyard,and producing a greater difference with outdoor temperatures that can reach 12℃versus 8℃for the reference *** addition,it was found that the courtyard with radiative cooling is able to significantly reduce the observed nighttime overheating by providing lower temperatures than the outdoor temperatures in the 50%of the nights *** was also found that the thermal loads to achieve indoor thermal comfort in the spaces adjacent to the courtyard were reduced by 63.46%to 69.85%.

关键词： radiative cooling passive cooling CFD three-dimensional modeling energy saving thermal comfort

Artificial intelligence for early detection of pancreatic adenocarcinoma: The future is promising

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World Journal of Gastroenterology 2021年第13期27卷 1283-1295页

作者： antonio mendoza Ladd David L Diehl Department of Internal Medicine Division of GastroenterologyTexas Tech University Health Sciences Center El PasoEl PasoTX 79905United States Department of Gastroenterology and Nutrition Geisinger Medical CenterDanvillePA 17822United States

Pancreatic ductal adenocarcinoma(PDAC) is a worldwide public health concern. Despite extensive research efforts toward improving diagnosis and treatment, the 5-year survival rate at best is approximately 15%. This dismal figure can be attributed to a variety of factors including lack of adequate screening methods, late symptom onset, and treatment resistance. Pancreatic ductal adenocarcinoma remains a grim diagnosis with a high mortality rate and a significant psychological burden for patients and their families. In recent years artificial intelligence(AI) has permeated the medical field at an accelerated pace, bringing potential new tools that carry the promise of improving diagnosis and treatment of a variety of diseases. In this review we will summarize the landscape of AI in diagnosis and treatment of PDAC.

关键词： Pancreatic adenocarcinoma Artificial intelligence Neural network Future perspectives Early diagnosis Improved performance

Endoscopic mucosal ablation-an alternative treatment for colonic polyps:Three case reports

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World Journal of Gastroenterology 2020年第45期26卷 7258-7262页

作者： antonio mendoza Ladd Joaquin Espinoza Cesar Garcia Department of Internal Medicine Division of GastroenterologyTexas Tech University Health Sciences CenterPaul L Foster School of MedicineEl PasoTX 79905United States Escuela de Medicina Luis Razetti Universidad Central de VenezuelaCaracas 999188Venezuela Department of Endoscopy University Medical Center of El PasoEl PasoTX 79905United States

BACKGROUND Endoscopic resection of non-invasive lesions is now the standard of care for lesions in the GI ***,resection techniques require extensive training,are not available in all endoscopy centers and are prone to *** mucosal ablation(EMA)is a combination of resection and ablation techniques and it may offer an alternative in the management of such *** SUMMARY In this case series we report the successful treatment of three flat colonic polyps using the EMA *** lesions were treatment naïve and 1 was a recurrence after an endoscopic mucosal *** sizes ranged from 2 to 4 *** three polyps were ablated successfully with no immediate or delayed *** recurrence rate at 1 year of follow up was 0%.CONCLUSION Based on this initial experience,we conclude that EMA is a safe and effective technique for the treatment of non-invasive colonic polyps when endoscopic resection techniques are not available.

关键词： Endoscopy Mucosal ablation Colon polyp Argon plasma coagulation Alternative Safe Case report

Optimal heat release shaping in a reactivity controlled compression ignition （RCCI） engine

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Control Theory and Technology 2017年第2期15卷 117-128页

作者： carlos GUARDIOLA Benjamin PLA antonio GARCiA Vicente BORONAT CMT-Motores Termicos Universitat Politecnica de Valencia Valencia Spain

The present paper addresses the optimal heat release （HR） law in a single cylinder engine operated under reactivity controlled compression ignition （RCCl） combustion mode to minimise the indicated specific fuel consumption （ISFC） subject to different constraints including pressure related limits （maximum cylinder pressure and maximum cylinder pressure gradient）. With this aim, a 0-dimensional （OD） engine combustion model has been identified with experimental data. Then, the optimal control problem of minimising the ISFC of the engine at different operating conditions of the engine operating map has been stated and analytically solved. To evaluate the method viability a data-driven model is developed to obtain the control actions （gasoline fraction） leading to the calculated optimal HR, more precisely to the optimal ratio between premixed and diffusive combustion. The experimental results obtained with such controls and the differences with the optimal HR are finally explained and discussed.

关键词： Diesel engine RCCI combustion analysis optimal control

COMPLEX SYSTEMS IN SPORTS:INTRODUCTION TO THE SPECIAL ISSUE

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Journal of Systems Science & Complexity 2013年第1期26卷 1-3页

作者： MERELO Juan Julin MORA antonio M COTTA carlos Depto.ATC CITICUniversidad de Granada Depto.LCC Universidad de Malaga

1 Complex Systems in Sports Sport is one of the most important activities of *** relevance goes beyond the physical/psychological benefits that their practicing provides(an aspect that justifies in itself its importance in our current society).In fact,be it as actually playing some sport or just watching some games,it provides a huge means for socialization and *** to say,the economical viewpoint is also enormously relevant:events such as the Olympic Games。

关键词：复杂系统运动教育手段社会化

A Finite Element Study of the Influence of Graphite Nodule Characteristics on a Subsurface Crack in a Ductile Cast Iron Matrix under a Contact Load

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Computer Modeling in Engineering & Sciences 2018年第10期117卷 59-71页

作者： Guilherme Suguinoshita carlos Henrique da Silva Marco antonio Luersen Department of Mechanical Engineering Federal University of Technology-Parana(UTFPR)Rua Deputado Heitor Alencar Furtado5000CEP 81280-340CuritibaBrazil

This paper describes a study of the effects of graphite nodule characteristics on a subsurface crack in austempered ductile iron(ADI).A representative specimen of ADI,subjected to sliding contact load,is modeled using finite elements aiming to obtain the shear stress intensity factor(KII).The parameters varied were(i)the nodule diameter(two different values were considered),(ii)the distance between the nodule and the tip of the crack and(iii)the position of the load relative to the tip of the *** results of the numerical simulations show that the smaller diameter nodule has a larger influence on KII,suggesting a higher contact fatigue crack propagation rate in the material with the smaller *** results are the opposite of those observed in experimental studies and would appear to indicate that other factors should be also considered to ensure realistic estimates of the contact fatigue strength of ADI.

关键词： Austempered ductile iron subsurface crack stress intensity factor finite element analysis graphite nodule