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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George d.Bittner department of Molecular Biosciences University of Texas at AustinAustinTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal regeneration.Furthermore,such peripheral nerve allografts undergo immunological rejection by the host immune system.In contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian degeneration.The relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this study.We hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral recovery.We examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal fusion.Ablation-type sciatic nerve injuries in outbred Sprague–dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host axons.Similar to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days postoperatively.Other morphological signs of rejection,such as collapsed Schwann cell basal lamina tubes,were abse

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

Adventures Beyond Amdahl's Law:How Power-Performance Measurement and Modeling at Scale drive Server and Supercomputer design

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Journal of Computer Science & Technology 2023年第1期38卷 80-86页

作者： Kirk W.cameron Computer Science Virginia TechWashington D.C.VA 24061U.S.A.

Amdahl’s Law painted a bleak picture for large-scale computing.The implication was that parallelism was limited and therefore so was potential speedup.While Amdahl’s contribution was seminal and important,it drove others vested in parallel processing to define more clearly why large-scale systems are critical to our future and how they fundamentally provide opportunities for speedup beyond Amdahl’s predictions.In the early 2000s,much like Amdahl,we predicted dire consequences for large-scale systems due to power limits.While our early work was often dismissed,the implications were clear to some:power would ultimately limit performance.In this retrospective,we discuss how power-performance measurement and modeling at scale led to contributions that have driven server and supercomputer design for more than a decade.While the influence of these techniques is now indisputable,we discuss their connections,limits and additional research directions necessary to continue the performance gains our industry is accustomed to.

关键词： Amdahl’s Law speedup power-aware computing power modeling performance modeling performance prediction power measurement

Polymer graph neural networks for multitask property learning

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npj Computational Materials 2023年第1期9卷 1420-1429页

作者： Owen Queen Gavin A.McCarver Saitheeraj Thatigotla Brendan P.Abolins cameron L.Brown Vasileios Maroulas Konstantinos d.Vogiatzis department of Mathematics University of TennesseeKnoxvilleTN 37996-1320USA department of Electrical Engineering and Computer Science University of TennesseeKnoxvilleTN 37996-2250USA department of Chemistry University of TennesseeKnoxvilleTN 37996-1600USA Eastman Chemical Company KingsportTN 37660USA

The prediction of a variety of polymer properties from their monomer composition has been a challenge for material informatics,and their development can lead to a more effective exploration of the material space.In this work,POLYMERGNN,a multitask machine learning architecture that relies on polymeric features and graph neural networks has been developed towards this goal.POLYMERGNN provides accurate estimates for polymer properties based on a database of complex and heterogeneous polyesters(linear/branched,homopolymers/copolymers)with experimentally refined properties.In POLYMERGNN,each polyester is represented as a set of monomer units,which are introduced as molecular graphs.A virtual screening of a large,computationally generated database with materials of variable composition was performed,a task that demonstrates the applicability of the POLYMERGNN on future studies that target the exploration of the polymer space.Finally,a discussion on the explainability of the models is provided.

关键词： properties space polyester

Progress of Pb-Sn Mixed Perovskites for Photovoltaics: A Review

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Energy & Environmental Materials 2022年第2期5卷 370-400页

作者： Rajapakshe Mudiyanselage Indrachapa Bandara Shashini M.Silva cameron C.L.Underwood K.d.G.Imalka Jayawardena Radu A.Sporea S.Ravi P.Silva Advanced Technology Institute Faculty of Engineering and Physical SciencesUniversity of SurreyGuildford Surrey GU27XHUnited Kingdom

Pb-Sn mixed perovskites are becoming increasingly popular as narrowbandgap(1.2–1.3 eV)light absorbers in single-junction perovskite solar cells(PSCs)and as bottom cells for all-perovskite tandem solar cells,for highefficiency,low-cost,lightweight,roll-to-roll printable photovoltaic(PV)applications.From the first report of planar Pb:Sn mixed PSCs in 2014,the power conversion efficiencies(PCE)have increased from 10%to 21%by the end of 2020 with an exponential growth in research conducted in this field.despite much effort,the performance and stability of Pb-Sn mixed PSCs are still limited,which constrains their long-term use in all-perovskite tandem devices.This review highlights the avenues explored in improving different aspects of Pb-Sn mixed PSCs and provides a comprehensive discussion of the interdependent factors affecting the device performance.This includes compositional engineering of the perovskite crystal,absorber layer fabrication and crystallization methods,bandgap tuning,Sn4+reduction,and surface passivation of the absorber layer,as well as the selection of interlayers and electrodes of the final PSC.

关键词： inorganic-organic hybrids lead-tin mixed perovskites perovskites photovoltaics solution-processed

Robust genome and RNA editing via CRISPR nucleases in PiggyBac systems

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Bioactive Materials 2022年第8期7卷 313-320页

作者： Yuqian Jiang Rachel Catherine Hoenisch Yun Chang Xiaoping Bao Craig E.cameron Xiaojun Lance Lian department of Biomedical Engineering Pennsylvania State UniversityUniversity ParkPA16802USA Huck Institutes of the Life Sciences Pennsylvania State UniversityUniversity ParkPA16802USA department of Biology Pennsylvania State UniversityUniversity ParkPA16802USA davidson School of Chemical Engineering Purdue UniversityWest LafayetteIN47907USA department of Microbiology and Immunology University of North Carolina School of MedicineChapel HillNC27599USA

CRISPR/Cas-mediated genome editing in human pluripotent stem cells(hPSCs)offers unprecedented opportunities for developing in vitro disease modeling,drug screening and cell-based therapies.To efficiently deliver the CRISPR components,here we developed two all-in-one vectors containing Cas9/gRNA and inducible Cas13d/gRNA cassettes for robust genome editing and RNA interference respectively.These vectors utilized the PiggyBac transposon system,which allows stable expression of CRISPR components in hPSCs.The Cas9 vector PB-CRISPR exhibited high efficiency(up to 99%)of inducing gene knockout in both protein-coding genes and long non-coding RNAs.The other inducible Cas13d vector achieved extremely high efficiency in RNA knockdown(98%knockdown for Cd90)with optimized gRNA designs.Taken together,our PiggyBac CRISPR vectors can serve as powerful toolkits for studying gene functions in hPSCs.

关键词： CRISPR-Cas9 Genome editing Cas13d RNA editing PiggyBac transposon Human pluripotent stem cells

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries

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Neural Regeneration Research 2018年第1期13卷 53-57页

作者： George d.Bittner dale R.Sengelaub cameron L.Ghergherehchi department of Neuroscience University of Texas at Austin department of Psychological and Brain Sciences Indiana University department of Molecular Biosciences University of Texas at Austin

Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce：（1） Immediate loss of axonal continuity, sensory signaling, and motor control; （2） Wallerian rapid （1-3 days） degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months （if ever, after ablations） by slowly-regenerating （1 mm/d）, proximal-stump outgrowths that must specifically reinnervate denervated targets; （3） Poor acceptance of microsutured nerve allografts, even if tissue-matched and immune-suppressed. Repair of transections/ablations by neurorrhaphy and well-specified-sequences of PEG-fusion solutions （one containing polyethylene glycol, PEG） successfully address these problems. However, conundrums and confusions regarding unorthodox and dramatic results of PEG-fusion repair in animal model systems often lead to misunderstandings. For example, （1） Axonal continuity and signaling is re-established within minutes by non-specifically PEG-fusing （connecting） severed motor and sensory axons across each lesion site, but remarkable behavioral recovery to near-unoperated levels takes several weeks; （2） Many distal stumps of inappropriately-reconnected, PEG-fused axons do not ever （Wallerian） degenerate and continuously innervate muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; （3） Host rats do not reject PEG-fused donor nerve allografts in a non-immuno-privileged environment with no tissue matching or immunosuppression; （4） PEG fuses apposed open axonal ends or seals each shut （thereby preventing PEG-fusion）, depending on the experimental protocol; （5） PEG-fusion protocols produce similar results in animal model systems and early human case studies. Hence, iconoclastic PEG-fusion data appropriately understood might provoke a re-thinking of some Neuroscience dogma and a paradigm shift in clinical treatment of peripheral nerve injuries.

关键词： axonal repair axotomy Wallerian degeneration polyethylene glycol allograft autograft nerve regeneration

Polyethylene glycol-fusion retards Wallerian degeneration and rapidly restores behaviors lost after nerve severance

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Neural Regeneration Research 2016年第2期11卷 217-219页

作者： George d.Bittner Michelle Mikesh cameron L.Ghergherehchi department of Neuroscience University of Texas at Austin

Some biological uses of polyethylene glycol（PEG）：The use of PEG as a membrane fusogen was first reported in 1976with the creation of cell hybrids,formed by suspending two cell lines in a 50%w/w solution of PEG in w... 详细信息

关键词： Figure PEG Polyethylene glycol-fusion retards Wallerian degeneration and rapidly restores behaviors lost after nerve severance

Avoiding artefacts in MicroCT imaging of collagen scaffolds:Effect of phosphotungstic acid(PTA)-staining and crosslink density

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Bioactive Materials 2022年第2期7卷 210-219页

作者： Kyung-Ah Kwon daniel V.Bax Jennifer H.Shepherd Ruth E.cameron Serena M.Best Cambridge Centre for Medical Materials Department of Materials Science and MetallurgyUniversity of CambridgeCambridgeUnited Kingdom School of Engineering University of LeicesterLeicesterUnited Kingdom

X-ray micro-computed tomography(μ-CT)can be used to provide both qualitative and quantitative information on the structure of three-dimensional(3d)bioactive scaffolds.When performed in a dry state,μ-CT accurately reflects the structure of collagen-based scaffolds,but imaging in a wet state offers challenges with radiolucency.Here we have used phosphotungstic acid(PTA)as a contrast agent to visualise fully hydrated collagen scaffolds in a physiologically relevant environment.A systematic investigation was performed to understand the effects of PTA on the results of μ-CT imaging by varying sample processing variables such as crosslinking density,hydration medium and staining duration.Immersing samples in 0.3% PTA solution overnight completely stained the samples and the treatment provided a successful route forμ-CT analysis of crosslinked samples.However,significant structural artefacts were observed for samples which were either non-crosslinked or had low levels of crosslinking,which had a heterogeneous interior architecture with collapsed pores at the scaffold periphery.This work highlights the importance of optimising the choice of processing and staining conditions to ensure accurate visualisation for hydrated 3d collagen scaffolds in an aqueous medium.

关键词： MicroCT crosslinking qualitative

Scavenger Receptor Class B type 1(SR-B1)and the modifiable risk factors of stroke

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Chinese Neurosurgical Journal 2020年第1期6卷 35-44页

作者： Lenahan cameron Huang Lei Travis Zachary d. Zhang John H. Burrell College of Osteopathic Medicine Las CrucesNM 88003USA Center for Neuroscience Research School of MedicineLoma Linda UniversityLoma LindaCA 92324USA department of Neurosurgery School of MedicineLoma Linda UniversityLoma LindaCA 92350USA department of Physiology&Pharmacology School of MedicineLoma Linda UniversityLoma LindaCA 92350USA department of Earth and Biological Sciences School of MedicineLoma Linda UniversityLoma LindaCA 92350USA department of Anesthesiology School of MedicineLoma Linda UniversityLoma LindaCA 92324USA

Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured,consequently leading to deficits in neurological function.Stroke consistently ranked as one of the top causes of mortality,and with the mean age of incidence decreasing,there is renewed interest to seek novel therapeutic treatments.The Scavenger Receptor Class B type 1(SR-B1)is a multifunctional protein found on the surface of a variety of cells.Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity.In this review,we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke.SR-B1 likely has an impact on stroke through its interaction with smoking,diabetes mellitus,diet,physical inactivity,obesity,hypercholesterolemia,atherosclerosis,coronary heart disease,hypertension,and sickle cell disease,all of which are critical risk factors in the pathogenesis of stroke.

关键词： Scavenger Receptor Class B type 1 SR-B1 Atherosclerosis Coronary heart disease diabetes mellitus Sickle cell Obesity Physical inactivity Hypercholesterolemia Hypertension