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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Global weirding at mass extinction horizons

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National Science Review 2024年第1期11卷 10-12页

作者： gregory j.Retallack Department of Earth Sciences University of Oregon

A strong motivation for studying mass extinctions is understanding how current climatic and biodiversity crises will affect creatures living on land such as ourselves. Perhaps the question is: how bad can it get? In that case, terrestrial Permian-Triassic mass extinctions are an irresistible worst-case scenario [1].

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The Emeishan large igneous province:A synthesis

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Geoscience Frontiers 2014年第3期5卷 369-394页

作者： j.gregory Shellnutt National Taiwan Normal University Department of Earth Science

The late Permian Emeishan large igneous province （EL1P） covers -0.3× 10-6 kmL of the western margin of the Yangtze Block and Tibetan Plateau with displaced, correlative units in northern Vietnam （Song Da zone）. The ELIP is of particular interest because it contains numerous world-class base metal deposits and is contemporaneous with the late Capitanian （-260 Ma） mass extinction. The flood basalts are the signature feature of the ELIP but there are also ultramafic and silicic volcanic rocks and layered mafic- ultramafic and silicic plutonic rocks exposed. The EL1P is divided into three nearly concentric zones （i.e. inner, middle and outer） which correspond to progressively thicker crust from the inner to the outer zone. The eruptive age of the ELIP is constrained by geological, paleomagnetic and geochronological evidence to an interval of 〈3 Ma. The presence of picritic rocks and thick piles of flood basalts testifies to high temperature thermal regime however there is uncertainty as to whether these magmas were derived from the subcontinental lithospheric mantle or sub-lithospheric mantle （i.e. asthenosphere or mantle plume） sources or both. The range of Sr （Isr ≈ 0.7040-0.7132）, Nd （ENd（t） ≈ -14 tO ＋8）, Pb （206-pb/204-pb1 ≈ 17.9-20.6） and Os （Yos ≈ -5 to ＋11） isotope values of the ultramafic and mafic rocks does not permit a conclusive answer to ultimate source origin of the primitive rocks but it is clear that some rocks were affected by crustal contamination and the presence of near-depleted isotope compo- sitions suggests that there is a sub-lithospheric mantle component in the system. The silicic rocks are derived by basaltic magmas/rocks through fractional crystallization or partial melting, crustal melting or by interactions between mafic and crustal melts. The formation of the Fe-Ti-V oxide-ore deposits is probably due to a combination of fractional crystallization of Ti-rich basalt and fluxing of C02-rich fluids whereas the Ni-Cu-（PGE） deposits are related

关键词： Late Permian Mantle plume Large igneous province Flood basalts Mineral deposits Uplift and doming

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Potential of the neonicotinoid imidacloprid and the oxadiazine indoxacarb for controlling five coleopteran pests of stored grain

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Insect Science 2012年第1期19卷 96-101页

作者： gregory j. Daglish Manoj K. Nayak Agri-Science Queensland Department of Employment Economic Development and Innovation Brisbane Queensland Australia

The potential for using imidacloprid （a neonicotinoid） and indoxacarb （an oxadiazine） as grain protectants was investigated in bioassays against resistant strains of five stored grain beetles. The species investigated were Rhyzopertha dominica （E）（the lesser grain borer）, Sitophilus oryzae （L.）（the rice weevil）, Tribolium castaneum （Herbst）（the rust-red flour beetle）, Oryzaephilus surinamensis （L.）（the saw tooth flour beetle）, and Cryptolestesferrugineus （Stephens）（the fiat grain beetle）. Each of these species has developed resistance to one or more protectants, including organophosphorus insecticides, synthetic pyrethroids and the juvenile hormone analogue methoprene. Mortality and re- production after a 2-week exposure of adults to treated wheat depended on species, dose and insecticide. Imidacloprid had no effect on S. oryzae at any dose, but none of the other species produced any live progeny at 10 mg/kg. Indoxacarb had no effect on T. castaneum at any dose, but none of the other species produced any live progeny at 5 mg/kg. The results show that although both imidacloprid and indoxacarb can control at least four of the five key pests tested at doses comparable to those used for organophosphorus protectants, more potent neonicotinoid or oxadiazine insecticides would be needed than either of these to provide broad spectrum protection of stored grain .

关键词： beetles imidacloprid indoxacarb stored grain

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Enhancing sintering resistance of atomically dispersed catalysts in reducing environments with organic monolayers

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Green Energy & Environment 2022年第6期7卷 1263-1269页

作者： jing Zhang Chithra Asokan gregory Zakem Phillip Christopher j.Will Medlin Department of Chemical and Biological Engineering University of ColoradoBoulderCOUSA Department of Chemical Engineering University of CaliforniaSanta BarbaraSanta BarbaraCAUSA

Atomically dispersed precious metal catalysts maximize atom efficiency and exhibit unique ***,they are susceptible to *** reactions occurring in reducing environments tend to result in atomically dispersed metals sintering at lower temperatures than in oxidative or inert atmospheres due to the formation of mobile metal-H or metal-CO ***,we develop a new approach to mitigate sintering of oxide supported atomically dispersed metals in a reducing atmosphere using organophosphonate self-assembled monolayers(SAMs).We demonstrate this for the case of atomically dispersed Rh on Al_(2)O_(3) and TiO_(2) using a combination of CO probe molecule FTIR,temperature programmed desorption,and alkene hydrogenation rate *** suggests that SAM functionalization of the oxide provides physical diffusion barriers for the metal and weakens the interactions between the reducing gas and metal,thereby discouraging the adsorbate-promoted diffusion of metal atoms on oxide *** results show that support functionalization by organic species can provide improved resistance to sintering of atomically dispersed metals with maintained catalytic reactivity.

关键词： Atomically dispersed catalysts Organic monolayers Rh Single atom catalysis Sintering

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Characterization of particle deposition during crossflow filtration as influenced by permeate flux and crossflow velocity using a microfluidic filtration system

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Frontiers of Chemical Science and Engineering 2021年第3期15卷 552-561页

作者： Hongzhan Di gregory j.O.Martin Dave E.Dunstan Department of Chemical and Biomolecular Engineering University of MelbourneParkvilleVictoria 3010Australia

Particle deposition during crossflow filtration is significantly influenced by the operating conditions,in particular the permeate flux and crossflow ***,there is a lack of detailed knowledge about how deposit layer structures and distributions depend on operating *** study uses a microfluidic visualisation filtration system to examine the influence of operating conditions on the deposition process during crossflow ultrafiltration from a microscopic *** the permeate flux caused an increasing amount of deposition and a thicker deposit *** crossflow velocities reduced the extent of *** degree of deposition varied over a range of operating conditions due to the altered hydrodynamic forces exerted on the particles,which can be examined by the deposition probability according to an existing *** on this,an empirical correlation between the deposition probability and volume of deposition as a function of filtration time was developed,which gave good agreement with experimental *** effect of solution conditions was also involved in this correlation as a interaction *** could be useful for predicting the dynamic deposition process during crossflow filtration over a range of operating and solution conditions.

关键词： particle deposition crossflow filtration microfluidics confocal microscopy

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Efficacy and dose response of Lactiplantibacillus plantarum in diarrhea-predominant irritable bowel syndrome

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World journal of Gastroenterology 2023年第28期29卷 4451-4465页

作者： Christopher j Martoni Shalini Srivastava Anders Damholt gregory j Leyer Clinical Development Human HealthChr.Hansen A/SHoersholm 2970Denmark Clinical Development Vedic LifesciencesMumbai 400053India Scientific Affairs Human HealthChr.Hansen A/SHoersholm 2970Denmark

BACKGROUND Probiotics have shown promise in alleviating symptoms of diarrhea-predominant irritable bowel syndrome(IBS-D);however,the certainty of evidence is *** randomized controlled dose-ranging trials are warranted on promising single-strain *** To investigate the clinical efficacy of Lactiplantibacillus plantarum(***)Lpla33(DSM34428)in adults with *** This is a randomized,double-blind,placebo-controlled,multi-center,and doseranging *** hundred and seven adults,18-70 years of age,with IBS-D,according to Rome IV criteria,were allocated(1:1:1)to receive placebo or *** Lpla33 at 1×10^(9)(1B)or 1×10^(10)(10B)colony-forming units/d over an 8-wk intervention *** primary outcome was the change in IBS severity scoring system(IBS-SSS)total score after 8 wk,while secondary and exploratory outcomes included abdominal pain severity,IBS related quality of life,stool and microbial profile,and perceived *** IBS-SSS was significantly reduced,after 8 wk,in participants receiving *** 1B(-128.45±83.30;Pwas observed,with a greater absolute reduction in the *** 10B group(Pwas observed in both *** groups compared to placebo(P<0.001).Further,62.5%and 88.4%of participants administered *** 1B and 10B,respectively,were classified as stool consistency responders based on a reduction in diarrheal stool form,as compared to 26.3%in the placebo group(P<0.001).In contrast,no significant shifts were observed in microbial *** *** Lpla33(DSM34428)is well tolerated and improves IBS symptom severity with a dose-ranging effect and a corresponding normalization of bowel habits in adults with IBS-D.

关键词： Randomized clinical trial Diarrhea-predominant irritable bowel syndrome Microbiome Probiotic Lactiplantibacillus plantarum

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A Rare Case of Concordant Atrioventricular Connection to L-Looped Ventricles in Situs Solitus:4-Dimensional Magnetic Resonance Imaging and 3D Printing

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Congenital Heart Disease 2022年第4期17卷 387-392页

作者： gregory Perens Takegawa Yoshida j.Paul Finn UCLA Mattel Children’s Hospital Children’s Heart CenterLos AngelesCAUSA Diagnostic Cardiovascular Imaging Laboratory Department of Radiology12222 David Geffen School of Medicine at UCLALos AngelesCAUSA

An infant male presented with the rare anatomy consisting of situs solitus,concordant atrioventricular connections to L-looped ventricles,double outlet right ventricle(DORV),and hypoplastic aortic arch.6 months after neonatal aortic arch repair,the morphologic right ventricle function deteriorated,and surgical evaluation was undertaken to determine if either biventricular repair with a systemic morphologic left ventricle or right ventricular exclusion was *** initial echocardiography,magnetic resonance imaging(MRI)was used to create detailed axial and 4-dimensional(4D)images and 3-dimensional(3D)printed *** detailed anatomy of this rare,complex case and its use in pre-surgical planning is presented.

关键词： Magnetic resonance imaging cardiac segments 3D printing

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Cysteine proteases as therapeutic targets:does selectivity matter? A systematic review of calpain and cathepsin inhibitors

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Acta Pharmaceutica Sinica B 2015年第6期5卷 506-519页

作者： Marton Siklos Manel Ben Aissa gregory R.j.Thatcher Department of Medicinal Chemistry and Pharmacognosy University of Illinois College of Pharmacy

Cysteine proteases continue to provide validated targets for treatment of human *** neurodegenerative disorders,multiple cysteine proteases provide targets for enzyme inhibitors,notably caspases,calpains,and *** reactive,active-site cysteine provides specificity for many inhibitor designs over other families of proteases,such as aspartate and serine;however,a)inhibitor strategies often use covalent enzyme modification,and b)obtaining selectivity within families of cysteine proteases and their isozymes is *** review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders;the latter focus providing an interesting query for the contemporary assumptions that irreversible,covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

关键词： Cysteine protease Calpain Cathepsin Enzyme inhibitors Neurodegeneration Alzheimer’s disease

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Data-Driven Microstructure and Microhardness Design in Additive Manufacturing Using a Self-Organizing Map

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Engineering 2019年第4期5卷 730-735页

作者： Zhengtao Gan Hengyang Li Sarah j.Wolff jennifer L.Bennett gregory Hyatt gregory j.wa.ner jian Cao Wing Kam Liu Department of Mechanical Engineering Northwestern UniversityEvanstonIL 60208USA DMG MORI Hoffman EstatesIL 60192USA

To design microstructure and microhardness in the additive manufacturing(AM)of nickel(Ni)-based superalloys,the present work develops a novel data-driven approach that combines physics-based models,experimental measurements,and a data-mining *** simulation is based on a computational thermal-fluid dynamics(CtFD)model,which can obtain thermal behavior,solidification parameters such as cooling rate,and the dilution of solidified *** on the computed thermal information,dendrite arm spacing and microhardness are estimated using well-tested mechanistic *** microstructure and microhardness are determined and compared with the simulated values for *** visualize process-structure-properties(PSPs)linkages,the simulation and experimental datasets are input to a data-mining model-a self-organizing map(SOM).The design windows of the process parameters under multiple objectives can be obtained from the visualized *** proposed approaches can be utilized in AM and other data-intensive ***-driven linkages between process,structure,and properties have the potential to benefit online process monitoring control in order to derive an ideal microstructure and mechanical properties.

关键词： Additive manufacturing Data science Multiphysics modeling Self-organizing map Microstructure Microhardness Ni-based superalloy

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