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A tissue-engineered rostral migratory stream for directed neuronal replacement

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Neural Regeneration Research 2018年第8期13卷 1327-1331页

作者： John C.O'donnell Kritika S.Katiyar Kate V.Panzer d.kacy cullen Center for Brain Injury & Repair Department of Neurosurgery Perelman School of Medicine University of Pennsylvania Center for Neurotrauma Neurodegeneration & Restoration Corporal Michael Crescenz Veterans Affairs Medical Center School of Biomedical Engineering Drexel University department of Bioengineering School of Engineering and Applied Science University of Pennsylvania

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mamma- lian brain--including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-en- gineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient＇s own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replace- ment following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-princi- ple evidence that it promotes and directs migration of immature neurons.

关键词： rostral migratory stream glial tube astrocyte neuroblast brain injury neural repair neural regeneration tissue engineering

Restoring nervous system structure and function using tissue engineered living scaffolds

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Neural Regeneration Research 2015年第5期10卷 679-685页

作者： Laura A.Struzyna James P.Harris Kritika S.Katiyar H.Isaac Chen d.kacy cullen Center for Brain Injury and Repair Department of NeurosurgeryPerelman School of MedicineUniversity of Pennsylvania Center for Neurotrauma Neurodegenerationand RestorationPhiladelphia Veterans Affairs Medical Center School of Biomedical Engineering Drexel University

Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

关键词： living scaffolds neural tissue engineering cell transplant biomaterials regeneration neurotrauma neurodegeneration axon pathfinding cell migration

Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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Bioactive Materials 2022年第12期7卷 339-353页

作者： Justin C.Burrell Suradip das Franco A.Laimo Kritika S.Katiyar Kevin d.Browne Robert B.Shultz Vishal J.Tien Phuong T.Vu dmitriy Petrov Zarina SAli Joseph M.Rosen d.kacy cullen Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA department of Bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova Medical LLCPhiladelphiaPAUSA dartmouth-Hitchcock Medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury Muscle preservation Tissue engineering Microtissue Axon fusion

Characterizing and modeling the precipitation of Mg-rich phases in Al 5xxx alloys aged at low temperatures

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Journal of Materials Science & Technology 2017年第9期33卷 991-1003页

作者： Gaosong Yi Weizhi Zeng Jonathan d.Poplawsky david A.cullen Zhifen Wangd Michael L.Free department of Metallurgical Engineering University of Utah Center for Nanophase Materials Sciences Oak Ridge National Laboratory Materials Science & Technology division Oak Ridge National Laboratory department of Metallurgical and Materials Engineering Colorado School of Mines

Al 5083 alloys(5.25 at.% Mg) of different tempers(H131 and H116) were aged at low temperatures(50and 70?C) for 41 months. Scanning transmission electron microscopy(STEM), energy-dispersive X-ray spectroscopy(EdS), and atom probe tomography(APT) were applied to characterize precipitates formed in the sensitized samples. Experimental results revealed that the size of Mg-rich precipitates increased with aging time at 70?C for both alloys. APT results showed that Mg-rich precipitates of different Mg concentrations and morphologies formed in Al matrix and on the interface of Al matrix/pre-existing particles. In addition, a model based on local equilibrium of chemical potential and multi-class precipitates number evolution was adopted to predict the multiphase precipitation process in the Al-Mg binary system. The overall trend of precipitate radius and number density predicted by the model matched well with the experimental results. Moreover, modeling results revealed that nucleation and coarsening occurred faster in Al 5083 H131 than in Al 5083 H116 when aged at same temperature. The high density of dislocations and the pipe diffusion mechanism of dislocations can be used to explain such behavior.

关键词： Al 5xxx alloys Precipitation Scanning transmission electron microscopy Atom probe tomography Long-term aging

Plasma-electrified up-carbonization for low-carbon clean energy

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Carbon Energy 2023年第1期5卷 25-70页

作者： Rusen Zhou Yadong Zhao Renwu Zhou Tianqi Zhang Patrick cullen Yao Zheng Liming dai Kostya(Ken)Ostrikov School of Food and Pharmacy Zhejiang Ocean UniversityZhoushanChina School of Chemistry and Physics Centre for Materials ScienceCentre for Clean Energy Technologies and PracticesCentre for Waste-Free-WorldQueensland University of Technology(QUT)BrisbaneQueenslandAustralia State Key Laboratory of Electrical Insulation and Power Equipment Center for Plasma BiomedicineXi'an Jiaotong UniversityXi'anShaanxiChina School of Chemical and Biomolecular Engineering The University of SydneySydneyNew South WalesAustralia School of Chemical Engineering and Advanced Materials The University of AdelaideAdelaideSouth AustraliaAustralia School of Chemical Engineering Australian Carbon Materials Centre(A-CMC)University of New South WalesSydneyNew South WalesAustralia

Low-value,renewable,carbon-rich resources,with different biomass feedstocks and their derivatives as typical examples,represent virtually inexhaustive carbon sources and carbon-related energy on *** conversion to higher-value forms(referred to as“up-carbonization”here),these abundant feedstocks provide viable opportunities for energy-rich fuels and sustainable platform chemicals ***,many of the current methods for such up-carbonization still lack sufficient energy,cost,and material efficiency,which affect their economics and carbon-emissions *** external electricity precisely delivered,discharge plasmas enable many stubborn reactions to occur under mild conditions,by creating locally intensified and highly reactive *** technology emerges as a novel,versatile technology platform for integrated or stand-alone conversion of carbon-rich *** plasma-based processes are compatible for integration with increasingly abundant and cost-effective renewable electricity,making the whole conversion carbon-neutral and further paving the plasma-electrified upcarbonization to be performance-,environment-,and *** the chief interest in this emerging area,no review article brings together the state-of-the-art results from diverse disciplines and underlies basic mechanisms and chemistry *** such,this review aims to fill this gap and provide basic guidelines for future research and transformation,by providing an overview of the application of plasma techniques for carbon-rich resource conversion,with particular focus on the perspective of discharge plasmas,the fundamentals of why plasmas are particularly suited for upcarbonization,and featured examples of plasma-enabled resource *** parallels drawn and specificity highlighted,we also discuss the technique shortcomings,current challenges,and research needs for future work.

关键词： carbon-rich resources discharge plasmas low-carbon energy power-to-X process electrification

Application of plasma-activated water for Escherichia coli decontamination and shelf-life extension of kale

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Food Quality and Safety 2022年第3期6卷 416-426页

作者： Hexiang Wang Yingxia Li Qian Xi Rongwei Han Patrick J.cullen Qijing du Yongxin Yang Fereidoun Forghani Jiacheng Zhang Jun Wang College ofFood Science and Engineering Qingdao Agricultural UniversityQingdaoChina College of Food Science and Engineering Tarim UniversityAlarChina School of Chemical and Biomolecular Engineering University of SydneySydneyNSWAustralia Molecular Epidemiology Inc.15300 Bothell Way NELake Forest ParkWAUSA Shandong Engineering Technology Research Center of Food Quality and Safety Control QingdaoChina Qingdao Engineering Research Centerof Food Quality and Safety Risk Assessment QingdaoChina

The aim of this study was to examine the effectiveness of plasma-activated water(PAW)for inactivating Escherichia coli(***)and retention of key quality factors for *** plasma discharge times(1,2,3,4,5,and 10 min)and different exposure times(2,4,6,8,10,and 15 min)were used to investigate the inactivation effect of *** spot-inoculated on *** influence of different exposure times on the pH,hardness and color of kale was studied *** addition,the effects of PAW on the shelf-life of kale over 12 d of storage at 4℃ were *** results showed that after the treatment of 5-PAW-8(8 min treatment by PAW generated by 5 min plasma discharge),the population of *** on kale was reduced by approximately 1.55 log colony-forming units(CFU)/g and the changes in pH,hardness and color of kale were not significant(P>0.05).during the storage period after 5-PAW-8 treatment,the hardness,weight loss,color,surface morphology and ascorbic acid were found to be better than those of the two control groups(Pd in pH values,the content of total phenols,or 1,1-dipheny1-2-picrylhydrazyl radical scavenging capacity(P>0.05).It is indicated that PAW treatment is a promising methodfor improving microbiological safety and extending the shelf-life of kale.

关键词： Plasma-activated water kale Escherichia coli shelf-life quality

Patterning Functionalized Surfaces of 2d Materials by Nanoshaving

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Nanomanufacturing and Metrology 2022年第1期5卷 23-31页

作者： Katie O'Neill Rob Greig Rita Tilmann Lisanne Peters Conor P.cullen Graeme Cunningham Cian Bartlam Cormac O Coileain Niall McEvoy Georg S.duesberg School of Physics Trinity College DublinDublin 2 D02 PN40Ireland AMBER Centre CRANN InstituteTrinity College DublinDublin 2Ireland Institute of Physics EIT 2Faculty of Electrical Engineering and Information TechnologyUniversitat der Bundeswehr Miinchen85579 NeubibergGermany School of Chemistry Trinity College DublinDublin 2Ireland

Atomic force microscopy(AFM)and scanning probe lithography can be used for the mechanical treatment of various surfaces,including polymers,metals,and *** technique of nanoshaving,in which materials are removed using the AFM tip,is employed in this work to produce nanopatterns of self-assembled monolayers(SAMs)on two-dimensional(2d)*** materials used are monolayers of transition metal dichalcogenides(TMds),namely,MoS_(2)and WS_(2),which are noncovalently functionalized with perylene diimide(PdI),a perylene *** approach involves rastering an AFM probe across the surface at a controlled increased load in ambient *** a result of the strong bond between PdI SAM and TMd,loads in excess of 1|1N are required to pattern the *** predefined patterns,including a grating pattern with feature sizes below 250 nm,are *** indicate the high precision of nanoshaving as an accurate and nondestructive lithographic technique for 2d *** work functions of shaved heterostructures are also examined using Kelvin probe force microscopy.

关键词： Nanoshaving AFM KPFM Perylene diimide 2d materials MoS_(2) WS_(2) Noncovalent functionalization

Comparison of novel tools with traditional cognitive tests in detecting delirium in elderly medical patients

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World Journal of Psychiatry 2020年第4期10卷 46-58页

作者： david J Meagher Henry O’Connell Maeve Leonard Olugbenga Williams Fahad Awan Chris Exton Michael Tenorio Margaret O’Connor Colum P dunne Walter cullen John McFarland dimitrios Adamis Cognitive Impairment Research Group Graduate Entry Medical SchoolUniversity of LimerickLimerick V94 YVHOIreland department of Computer Sciences University of LimerickLimerick V94 YVHOIreland School of Medicine University College DublinDublin 4 D04 V1W8Ireland Sligo Mental Health Services BallytivanSligo F91 CD34Ireland

BACKGROUNd Efficient detection of delirium and comorbid delirium-dementia is a key diagnostic *** of new,efficient delirium-focused methods of cognitive assessment is a key challenge for improved detection of neurocognitive disorders in everyday clinical *** To compare the accuracy of two novel bedside tests of attention,vigilance and visuospatial function with conventional bedside cognitive tests in identifying delirium in older hospitalized *** 180 consecutive elderly medical inpatients(mean age 79.6±7.2;51%female)referred to a psychiatry for later life consultation-liaison service with delirium,dementia,comorbid delirium-dementia and cognitively intact *** were assessed cross-sectionally with conventional bedside cognitive tests[WORLd,Months Backward test(MBT),Spatial span,Vigilance A and B,Clock drawing test and Interlocking Pentagons test]and two novel cognitive tests[Lighthouse test,Letter and Shape drawing test(LSd)-4].RESULTS Neurocognitive diagnoses were delirium(n=44),dementia(n=30),comorbid delirium-dementia(n=60)and no neurocognitive disorder(n=46).All conventional tests had sensitivity of>70%for delirium,with best overall accuracy for the Vigilance-B(78.3%),Vigilance-A(77.8%)and MBT(76.7%)*** sustained attention component of the Lighthouse test was the most distinguishing of delirium(sensitivity 84.6%;overall accuracy 75.6%).The LSd-4 had sensitivity of 74.0%and overall accuracy 74.4%for delirium *** tests allowed for enhanced sensitivity(>90%)and overall accuracy(≥75%)with the highest overall accuracy for the combination of MBT-Vigilance A and the combined Vigilance A and B tests(both 78.3%).When analyses were repeated for those with dementia,there were similar findings with the MBTVigilance A the most accurate overall combination(80.0%).Combining the Lighthouse-SA with the LSd-4,a fail in either test had sensitivity for delirium of 91.4 with overall accuracy of 74.4%.

关键词： Visuospatial function Attention Vigilance Letter and Shape drawing test Lighthouse test delirium dementia Phenomenology Assessment

Whole-genome sequences shed light on the demographic history and contemporary genetic erosion of free-ranging jaguar(Panthera onca) populations

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Journal of Genetics and Genomics 2022年第1期49卷 77-80页

作者： Gustavo P.Lorenzana Henrique V.Figueirò Jeremy Johnson Elinor Karlsson Ronaldo G.Morato dênis A.Sana Laury cullen Joares A.May Jr. Edsel A.Moraes Jr. daniel L.Z.Kantek Leandro Silveira William J.Murphy Oliver A.Ryder Eduardo Eizirik Pontiﬁcal Catholic University of Rio Grande do Sul PUCRS.School of Health and Life SciencesPorto AlegreRS 90619Brazil Christopher B.Kaelin Gregory S.Barsh HudsonAlpha Institute for BiotechnologyHuntsvilleAL 35806USA Vertebrate Genome Biology Broad InstituteCambridgeMA 02142USA CENAP/ICMBio AtibaiaSP 12952Brazil PPG Biologia Animal Instituto de Bioci^enciasUFRGSPorto AlegreRS 90650Brazil Instituto de Pesquisas Ecol ogicas Teodoro SampaioSP 19280Brazil UniSul TubarãoSC 88704Brazil Instituto Prò-CarnivorosAtibaiaSP 12945Brazil Instituto Biotr opicos DiamantinaMG39100Brazil Estacão Ecologica de Taiamã ICMBioCaceresMT 78200Brazil Instituto Onca-pintada-Jaguar Conservation Fund MineirosGO 75830Brazil Texas A&M University College StationTX 77843USA San diego Zoo Institute for Conservation Research San DiegoCA 92027USA Pontiﬁcal Catholic University of Rio Grande do Sul PUCRS.School of Health and Life SciencesPorto AlegreRS 90619Brazil Instituto Pr o-Carni¬vorosAtibaiaSP 12945Brazil Centro Regional del Bajio INECOLP atzcuaroMIC61600Mexico Smithsonian Conservation Biology Institute WashingtonDC20008USA

Whole-genome sequences provide massive amounts of data that can illuminate many aspects of a species’biology and evolutionary history,as well as valuable information for conservation *** is particularly important for large carnivores,whose large area requirements and typical low densities make them prone to undergo rapid genetic erosion(*** of runs of homozygosity,diez del Molino et al.,2018;Leroy et al.,2018)in the face of habitat loss and human *** such species is the jaguar(Pan-thera onca),the largest extant felid in the Americas,whose range has already declined by>50%and some of whose remaining popu-lations have been severely impacted by human-induced habitat frag-mentation(de La Torre et al.,2018).

关键词： Whole habitat erosion