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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

High-resolution geological maps of central London, UK： Comparisons with the London Underground

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Geoscience Frontiers 2016年第2期7卷 273-286页

作者： jonathan d. Paul department of Earth Sciences Bullard Laboratories University of Cambridge Madingley Rise Cambridge CB3 0EZ UK

This study presents new thickness maps of post-Cretaceous sedimentary strata beneath central London. 〉1100 borehole records were analysed. London Clay is thickest in the west; thicker deposits extend as a narrow finger along the axis of the London Basin. More minor variations are probably governed by periglacial erosion and faulting. A shallow anticline in the Chalk in north-central London has resulted in a pronounced thinning of succeeding strata. These results are compared to the position of London Underground railway tunnels. Although tunnels have been bored through the upper levels of London Clay where thick, some tunnels and stations are positioned within the underlying, more lithologically variable, Lower London Tertiary deposits. Although less complex than other geological models of the London Basin, this technique is more objective and uses a higher density of borehole data. The high resolution of the resulting maps emphasises the power of modelling an expansive dataset in a rigorous but simnle fashion.

关键词： London London Underground London Clay Lambeth Group Chalk Tunnelling Boreholes

Hierarchical methodology to evaluate the quality of disparate axle load data sources for pavement design

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Journal of Traffic and Transportation Engineering(English Edition) 2022年第2期9卷 261-279页

作者： Steven Wood jonathan d.Regehr Transportation division City of WinnipegWinnipegMB R3B 1B9Canada department of Civil Engineering University of ManitobaMB R3T 5V6Canada

Axle load data are an essential input for pavement design,yet for most North American agencies,there is uncertainty about the quality of axle load data obtained from weigh-inmotion(WIM)systems,the applicability of these data for pavement design,and potential opportunities to integrate axle load data from disparate *** article presents a novel and practical methodology to evaluate the quality of axle load data from WIM systems and roadside weigh scales through a series of hierarchical analyses designed to test data *** applied using data from Manitoba,Canada,the methodology quantified the uncertainty of axle loads measured at the weigh scales and piezo-quartz WIM,concluding that both could be used for pavement design *** collected at piezo-polymer WIM sites exhibited poorer data validity;however,application of site-specific temperature correction factors significantly improved data validity at these *** article describes how other data quality dimensions,including spatial coverage,temporal coverage,and long-term data availability,could be considered when determining the suitability of disparate axle load data sources for pavement *** of the methodology enables a pragmatic evaluation of the quality and limitations of commonlyavailable axle load data,revealing uncertainties and data needs relevant for pavement design practice.

关键词： Road engineering Pavement design Axle load Weigh-in-motion data quality Truck traffic

On the calibration of a shear stress criterion for rock joints to represent the full stress-strain profile

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第2期16卷 379-392页

作者： Akram deiminiat jonathan d.Aubertin Yannic Ethier department of Construction Engineering École de Technologie Supérieure(ÉTS)MontréalCanada

Conventional numerical solutions developed to describe the geomechanical behavior of rock interfaces subjected to differential load emphasize peak and residual shear *** detailed analysis of preand post-peak shear stress-displacement behavior is central to various time-dependent and dynamic rock mechanic problems such as rockbursts and structural instabilities in highly stressed *** complete stress-displacement surface(CSdS)model was developed to describe analytically the pre-and post-peak behavior of rock interfaces under differential *** formulations of the CSdS model required extensive curve-fitting iterations which limited its practical applicability and transparent integration into engineering *** present work proposes modifications to the CSdS model aimed at developing a comprehensive and modern calibration protocol to describe the complete shear stressdisplacement behavior of rock interfaces under differential *** proposed update to the CSdS model incorporates the concept of mobilized shear strength to enhance the post-peak ***’s concepts of joint roughness coefficient(JRC)and joint compressive strength(JCS)are incorporated to facilitate empirical estimations for peak shear stress and normal closure ***/uniaxial compression test and direct shear test results are used to validate the updated model and exemplify the proposed calibration *** results illustrate that the revised model successfully predicts the post-peak and complete axial stressestrain and shear stressedisplacement curves for rock joints.

关键词： Full shear profile Post-peak shear behavior Rock joint Joint roughness coefficient(JRC) Axial stress-strain curve

Reduced texaphyrin:A ratiometric optical sensor for heavy metals in aqueous solution

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Frontiers of Chemical Science and Engineering 2020年第1期14卷 19-27页

作者： Harrison d.Root Gregory Thiabaud jonathan L.Sessler department of Chemistry The University of Texas at AustinAustinTX 78712-1224USA

We report here a water-soluble metal cation sensor system based on the as-prepared or reduced form of an expanded porphyrin,*** metal complexation,a change in the redox state of the ligand occurs that is accompanied by a color change from red to *** long employed for synthesis in organic media,we have now found that this complexation-driven redox behavior may be used to achieve the naked eye detectable colorimetric sensing of several number of less-common metal ions in aqueous *** to In(Ⅲ),Hg(Ⅱ),Cd(Ⅱ),Mn(Ⅱ),Bi(Ⅲ),Co(Ⅱ),and Pb(Ⅱ)cations leads to a colorimetric response within 10 *** process is selective for Hg(Ⅱ)under conditions of competitive ***,among the subset of responseproducing cations,In(Ⅲ)proved unique in giving rise to a ratiometric change in the ligand-based fluorescence features,including an overall increase in *** cation selectivity observed in aqueous media stands in contrast to what is seen in organic solvents,where a wide range of texaphyrin metal complexes may be *** formation of metal cation complexes under the present aqueous conditions was confirmed by reversed phase highperformance liquid chromatography,ultra-violet-visible absorption and fluorescence spectroscopies,and highresolution mass spectrometry.

关键词： texaphyrin fluorescent sensor ion-sensing indium mercury

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

Convergence detection in direct Simulation Monte Carlo Calculations for Steady State Flows

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Communications in Computational Physics 2011年第9期10卷 807-822页

作者： jonathan M.Burt Iain d.Boyd U.S.Air Force Research Laboratory Wright-Patterson Air Force BaseOH 45433USA department of Aerospace Engineering University of Michigan1320 Beal AvenueAnn ArborMI 48109USA

A new criterion is presented to detect global convergence to steady state,and to identify local transient characteristics,during rarefied gas flow simulations performed using the direct simulation Monte Carlo(dSMC)*** deterministic computational fluid dynamics(CFd)schemes,dSMC is generally subject to large statistical scatter in instantaneous flow property evaluations,which prevents the use of residual tracking procedures as are often employed in CFd ***,reliable prediction of the time to reach steady state is necessary for initialization of dSMC sampling *** currently used in dSMC to identify steady state convergence are usually insensitive to weak transient behavior in small regions of relatively low density or recirculating *** proposed convergence criterion is developed with the goal of properly identifying such weak transient behavior,while adding negligible computational expense and allowing simple implementation in any existing dSMC *** of the proposed technique over existing convergence detection methods are demonstrated for representative nozzle/plume expansion flow,hypersonic blunt body flow and driven cavity flow problems.

关键词： Monte Carlo methods particle methods direct simulation Monte Carlo

Microfluidic bacterial traps for simultaneous fluorescence and atomic force microscopy

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Nano Research 2017年第11期10卷 3896-3908页

作者： Oliver Peric Melanie Hannebelle jonathan d. Adams Georg E. Fantner Laboratory for Bio-and Nano-Instrumentation Institute of Bioengineering School of Engineering EPFL 1015 Lausanne Switzerland

The atomic force microscope has become an established research tool for imaging microorganisms with unprecedented ***,its use in microbiology has been limited by the difficulty of proper bacterial ***,we have developed a microfluidic device that solves the issue of bacterial immobilization for atomic force microscopy under physiological *** device is able to rapidly immobilize bacteria in well-defined positions and subsequently release the cells for quick sample *** developed device also allows simultaneous fluorescence analysis to assess the bacterial viability during atomic force microscope *** demonstrated the potential of our approach for the immobilization of rod-shaped Escherichia coli and Bacillus *** our device,we observed buffer-dependent morphological changes of the bacterial envelope mediated by the antimicrobial peptide *** approach to bacterial immobilization makes sample preparation much simpler and more reliable,thereby accelerating atomic force microscopy studies at the single-cell level.

关键词： atomic force microscope (AFM) microfabrication microfluidics microbiology correlative microscopy physical immobilization