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A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： John Mitrofanis jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

Wilson's disease in two siblings from Ecuador:Two case reports

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World Journal of Clinical Cases 2025年第3期13卷 50-60页

作者： Enrique Carrera jonathan Alvarado Martina Astudillo Galo Pillajo Department of Gastroenterology and Hepatology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador Faculty of Medicine Pontificia Universidad Catolica del EcuadorQuito 170143PichinchaEcuador Department of Radiology Hospital de Especialidades Eugenio EspejoQuito 170136PichinchaEcuador

BACKGROUND Wilson's disease(WD)is a rare metabolic disorder of copper accumulation in organs such as liver,brain,and *** and treatments are challenging in settings,where advanced diagnostic tests are unavailable,copper chelating agents are frequently scarce,healthcare professionals lack disease awareness,and medical follow-ups are *** diagnoses and treatments help prevent complications,improve patients’quality of life,and ensure a normal life *** clinical presentations and outcomes of WD can vary within a single *** SUMMARY We present the cases of two siblings(19 and 27 years)from a consanguineous family in rural Ecuador,diagnosed as having WD during a family *** male patient,diagnosed at age 19 after his brother’s death from acute liver failure,presented with compensated cirrhosis,neurological symptoms,and bilateral Kayser-Fleischer *** developed progressive neurological deterioration during an irregular treatment with D-penicillamine due to medication *** condition improved upon switching to trientine tetrahydrochloride,and his neurological symptoms improved over an 8-year period of *** female patient,diagnosed at age 10,exhibited only biochemical *** treatment history was similar;however,she remained asymptomatic without disease progression over the same follow-up *** discuss the potential influence of epigenetic mechanisms and modifier genes on the various phenotypes,emphasizing the need for research in these areas to optimize therapeutic *** Our patients’medical histories show how early diagnosis and treatment can prevent disease progression;and,how suboptimal treatments impact disease outcomes.

关键词： Wilson disease Kayser-Fleischer rings Copper chelator D-penicillamine Trientine tetrahydrochloride Case report

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

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Neural Regeneration Research 2025年第5期20卷 1324-1335页

作者： Hassan Saad Bachar El Baba Ali Tfaily Firas Kobeissy Juanmarco Gutierrez Gonzalez Daniel Refai Gerald R.Rodts Christian Mustroph David Gimbel jonathan Grossberg Daniel L.Barrow Matthew F.Gary Ali M.Alawieh Department of Neurosurgery Emory University School of MedicineAtlantaGAUSA Department of Neurology Yale UniversityNew HavenCTUSA Center for Neurotrauma Multiomics&Biomarkers(CNMB)Morehouse School of MedicineAtlantaGAUSA

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this *** the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing *** this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the *** study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular *** effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord *** this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human *** review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

关键词： complement neuroinflammation neuroplasticity regeneration spinal cord injury targeted therapy

The Need for Fuzzy AI

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IEEE/CAA Journal of Automatica Sinica 2019年第3期6卷 610-622页

作者： jonathan M.Garibaldi IEEE the School of Computer Science University of Nottingham

Artificial intelligence(AI) is once again a topic of huge interest for computer scientists around the world. Whilst advances in the capability of machines are being made all around the world at an incredible rate, there is also increasing focus on the need for computerised systems to be able to explain their decisions, at least to some degree. It is also clear that data and knowledge in the real world are characterised by *** systems can provide decision support, which both handle uncertainty and have explicit representations of uncertain knowledge and inference processes. However, it is not yet clear how any decision support systems, including those featuring fuzzy methods, should be evaluated as to whether their use is *** paper presents a conceptual framework of indistinguishability as the key component of the evaluation of computerised decision support systems. Case studies are presented in which it has been clearly demonstrated that human expert performance is less than perfect, together with techniques that may enable fuzzy systems to emulate human-level performance including *** conclusion, this paper argues for the need for "fuzzy AI" in two senses:(i) the need for fuzzy methodologies(in the technical sense of Zadeh's fuzzy sets and systems) as knowledge-based systems to represent and reason with uncertainty; and(ii) the need for fuzziness(in the non-technical sense) with an acceptance of imperfect performance in evaluating AI systems.

关键词： Artificial intelligence approximate reasoning fuzzy inference systems fuzzy sets human reasoning

Experimental investigations of a full model with adaptive elasto-flexible membrane wings

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Chinese Journal of Aeronautics 2021年第7期34卷 211-218页

作者： jonathan PFLU GER Christian BREITSAMTER Chair of Aerodynamics and Fluid Mechanics Technical University of MunichGarching 85748Germany

The morphing wing concept aims to constantly adapt the aerodynamics to different flight *** wing is able to adapt to different flight conditions by an adjustable Aspect Ratio(AR)and sweep.A high AR configuration provides high aerodynamic efficiency,while a low AR configuration,with highly swept wings offers a good ***,the flexible membrane allows the wing surface to stretch and contract in-plane as well as the airfoil to adapt to different aerodynamic *** the context of this work,the aerodynamic characteristics of a full model with form-adaptive elasto-flexible membrane wings are investigated *** focus is on the high-lift regime and on the analysis of the aerodynamic coefficients as well as their ***,the lateral aerodynamic derivatives at asymmetric wing positions are of interest.

关键词： Experimental aerodynamics Flexible wing surface Force and moment measurements Morphing wing Particle image velocimetry

Gust response of an elasto-flexible morphing wing using fluid–structure interaction simulations

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Chinese Journal of Aeronautics 2024年第2期37卷 45-57页

作者： jonathan PFLÜGER Christian BREITSAMTER Department of Mechanical Engineering Technical University of MunichGarching 85748Germany

Small and micro unmanned aircraft are the focus of scientific interest due to their wide range of *** often operate in a highly unstable flight environment where the application of new morphing wing technologies offers the opportunity to improve flight *** investigated concept comprises port and starboard adjustable wings,and an adaptive elastoflexible membrane serves as the lifting *** focus is on the benefits of the deforming membrane during the impact of a one-minus-cosine type *** a low Reynolds number of Re=264000,the morphing wing model is investigated numerically by unsteady fluid-structure interaction ***,the numerical results are validated by experimental data from force and moment,flow field,and deformation ***,with the rigid wing as the baseline,the flexible case is investigated,focusing on the advantages of the elastic *** all configurations studied,the maximum amplitude of the lift coefficient under gust load shows good agreement between the experimental and numerical *** the decay of the gust,they differ more the higher the aspect ratio of the *** considering the flow field,the main differences are due to the separation behavior on the upper side of the *** flow reattaches earlier in the experiments than in the simulations,which explains the higher lift values observed in the *** at one intermediate configuration does the lift amplitude of the rigid configuration exceeds that of the flexible by about 12%,with the elastic membrane resulting in a smaller and more uniform peak load,which is also evident in the wing loading and hence in the root bending moment.

关键词： Membrane wing Morphing wing Flexible wing surface Computational fluid dynam-ics Fluid-structure interaction Unsteady inflow condition Gust response

Biomedical engineering and erectile restoration:design considerations for urologic prosthetics

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Asian Journal of Andrology 2020年第1期22卷 15-19页

作者： jonathan J Lund Prosthetic Urology Research and Development Boston ScientificMinnetonkaMN 55343USA

For patients with moderate-to-severe erectile dysfunction,implantable penile prostheses continue to be a viable *** device developers apply design controls during the development cycle to ensure that a product performs as intended in the final use *** process relies heavily on the principles of systems engineering and documents every facet of performance,unmet need,and *** better understand design philosophy,it is important to frame benchmarked performance outcomes in the context of the ideal *** consideration of erectile anatomy and physiology,including flaccid state,transitional phases,and full tumescence,informs penile prosthesis design philosophy and provides the foundation for product advancement.

关键词： design controls engineering fluid dynamics inflatable penile prosthesis systems engineering

Formation of efficient dye-sensitized solar cells by introducing an interfacial layer of hierarchically ordered macro-mesoporous TiO_2 film

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Science China Chemistry 2011年第6期54卷 930-935页

作者： HALPERT jonathan E State Key Laboratory of Multi-phase Complex Systems Institute of Process Engineering Chinese Academy of Sciences

Hierarchically ordered macro-mesoporous TiO2 films (Ti-Ma-Me) were fabricated on fluorine-doped tin oxide (FTO) substrates through the confinement self-assembly method. The prepared Ti-Ma-Me possesses periodically ordered structure and a large specific surface area, which was applied as an interfacial layer between the nanocrystalline TiO2 film (P25-TiO2) and FTO electrode in the dye-sensitized solar cell (DSSC). The introduction of a Ti-Ma-Me interfacial layer increased the shortcircuit current density (Jsc) from 7.49 to 10.65 mA/cm2 and the open-circuit voltage (Voc) from 0.65 to 0.70 V as the result of its improved light harvesting efficiency by allowing for the high roughness factor and enhanced multiple internal reflection or scattering as well as reducing the back-transport reaction by blocking direct contact between the electrolyte and FTO electrode. Therefore, the photovoltaic conversion efficiency (η) was improved by 83% from 3.04% to 5.55%, as compared to a device using a bare P25 TiO2 photoanode.

关键词： dye-sensitized solar cells hierarchical ordered macro-mesoporous photoanode

ACCELERATED OPTIMIZATION WITH ORTHOGONALITY CONSTRAINTS

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Journal of Computational Mathematics 2021年第2期39卷 207-226页

作者： jonathan W.Siegel Department of Mathematics Pennsylvania State UniversityUniversity ParkPAUSA

We develop a generalization of Nesterov’s accelerated gradient descent method which is designed to deal with orthogonality *** demonstrate the effectiveness of our method,we perform numerical experiments which demonstrate that the number of iterations scales with the square root of the condition number,and also compare with existing state-of-the-art quasi-Newton methods on the Stiefel *** experiments show that our method outperforms existing state-of-the-art quasi-Newton methods on some large,ill-conditioned problems.

关键词： Riemannian optimization Stiefel manifold Accelerated gradient descent Eigenvector problems Electronic structure calculations