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Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina

Neural Regeneration Research 2023年第5期18卷 1004-1008页

作者： Yukitoshi Izumi Makoto Ishikawa Toru Nakazawa Hiroshi Kunikata Kota Sato douglas f.covey Charles f.Zorumski Department of Psychiatry and Taylor family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA Department of Ophthalmic Imaging and Information Analytics Tohoku University Graduate School of MedicineSendaiJapan Department of Ophthalmology Tohoku University Graduate School of MedicineSendaiJapan Department of Retinal Disease Control Tohoku University Graduate School of MedicineSendaiJapan Department of Advanced Ophthalmic Medicine Tohoku University Graduate School of MedicineSendaiJapan Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric conditions and results in neuronal and axonal changes that mimic glaucoma. We have used this model to determine neuroprotective mechanisms that could have therapeutic implications. In particular, we have focused on the role of both endogenous and exogenous neurosteroids in modulating the effects of acute high pressure. Endogenous allopregnanolone, a major stress-activated neurosteroid in the brain and retina, helps to prevent severe pressure-induced retinal excitotoxicity but is unable to protect against degenerative changes in ganglion cells and their axons under hyperbaric conditions. However, exogenous allopregnanolone, at a pharmacological concentration, completely preserves retinal structure and does so by combined effects on gamma-aminobutyric acid type A receptors and stimulation of the cellular process of macroautophagy. Surprisingly, the enantiomer of allopregnanolone, which is inactive at gamma-aminobutyric acid type A receptors, is equally retinoprotective and acts primarily via autophagy. Both enantiomers are also equally effective in preserving retinal structure and function in an in vivo glaucoma model. These studies in the retina have important implications for the ongoing development of allopregnanolone and other neurosteroids as therapeutics for neuropsychiatric illnesses.

关键词： allopregnanolone autophagy enantiomers excitotoxicity gamma-aminobutyric acid type A receptors glaucoma optic nerve oxysterols

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Current issues in endoscope reprocessing and infection control during gastrointestinal endoscopy

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World Journal of Gastroenterology 2006年第25期12卷 3953-3964页

作者： douglas B Nelson Lawrence f Muscarella Staff Physician in Gastroenterology Minneapolis VA Medical Center University of MinnesotaMinneapolisMN 55417United States Director Research and Development ChiefInfection ControlCustom UltrasonicsInc

The purpose of this article is to review the evidence regarding transmission of infection during gastrointestinal endoscopy, factors important in endoscope reprocessing and infection control, areas to focus on to impr... 详细信息

关键词： Endoscopy Infection Disinfection Reprocessing Infection control

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Operator Splitting for Three-Phase flow in Heterogeneous Porous Media

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Communications in Computational Physics 2009年第6期6卷 72-84页

作者： E.Abreu J.douglas f.furtado f.Pereira Instituto Nacional de Matematica Pura e Aplicada RJ 22460-320Brazil Department of Mathematics Purdue UniversityWest LafayetteIN 47907-1395USA Department of Mathematics University of WyomingLaramieWY 82071-3036USA Department of Mathematics and School of Energy Resources University of WyomingLaramieWY 82071-3036USA

We describe an operator splitting technique based on physics rather than on dimension for the numerical solution of a nonlinear system of partial differential equations which models three-phase flow through heterogeneous porous *** model for three-phase flow considered in this work takes into account capillary forces,general relations for the relative permeability functions and variable porosity and permeability *** our numerical procedure a high resolution,nonoscillatory,second order,conservative central difference scheme is used for the approximation of the nonlinear system of hyperbolic conservation laws modeling the convective transport of the fluid *** scheme is combined with locally conservative mixed finite elements for the numerical solution of the parabolic and elliptic problems associated with the diffusive transport of fluid phases and the pressure-velocity *** numerical procedure has been used to investigate the existence and stability of nonclassical shock waves(called transitional or undercompressive shock waves)in two-dimensional heterogeneous flows,thereby extending previous results for one-dimensional flow *** experiments indicate that the operator splitting technique discussed here leads to computational efficiency and accurate numerical results.

关键词： Operator splitting three-phase flow heterogeneous porous media central differencing schemes mixed finite elements

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forests,atmospheric water and an uncertain future: the new biology of the global water cycle

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forest Ecosystems 2018年第3期5卷 236-257页

作者： douglas Sheil faculty of Environmental Sciences and Natural Resource Management(MINA) Norwegian University of Life Sciences (NMBU)

Theory and evidence indicate that trees and other vegetation influence the atmospheric water-cycle in various *** influences are more important, more complex, and more poorly characterised than is widely *** there is little doubt that changes in tree cover will impact the water-cycle, the wider consequences remain difficult to predict as the underlying relationships and processes remain poorly characterised. Nonetheless, as forests are vulnerable to human activities, these linked aspects of the water-cycle are also at risk and the potential consequences of large scale forest loss are severe. Here, for non-specialist readers, I review our knowledge of the links between vegetation-cover and climate with a focus on forests and rain(precipitation). I highlight advances, uncertainties and research opportunities. There are significant shortcomings in our understanding of the atmospheric hydrological cycle and of its representation in climate models. A better understanding of the role of vegetation and tree-cover wil reduce some of these shortcomings. I outline and il ustrate various research themes where these advances may be *** themes include the biology of evaporation, aerosols and atmospheric motion, as well as the processes that determine monsoons and diurnal precipitation cycles. A novel theory—the ‘biotic pump’—suggests that evaporation and condensation can exert a major influence over atmospheric dynamics. This theory explains how high rainfall can be maintained within those continental land-masses that are sufficiently forested. feedbacks within many of these processes can result in non-linear behaviours and the potential for dramatic changes as a result of forest loss(or gain): for example, switching from a wet to a dry local climate(or visa-versa). Much remains unknown and multiple research disciplines are needed to address this: forest scientists and other biologists have a major role to *** ideas, methods and data offer opportun

关键词： Biotic pump Climate Condensation Evaporation Ice-nucleation Transpiration GCM Vapour Water-cycle

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Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system

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Translational Neurodegeneration 2022年第1期11卷 667-689页

作者： douglas M.Lopes Sophie K.Llewellyn Ian f.Harrison Division of Medicine Department of ImagingCentre for Advanced Biomedical ImagingFaculty of Medical SciencesUniversity College LondonPaul O’Gorman Building72 Huntley StreetLondon WC1E 6DDUK

Many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are characterised by the accumulation of misfolded protein deposits in the brain, leading to a progressive destabilisation of the neuronal network and neuronal death. Among the proteins that can abnormally accumulate are tau and α-synuclein, which can propagate in a prion-like manner and which upon aggregation, represent the most common intracellular proteinaceous lesions associated with neurodegeneration. for years it was thought that these intracellular proteins and their accumulation had no immediate relationship with extracellular homeostasis pathways such as the glymphatic clearance system;however, mounting evidence has now suggested that this is not the case. The involvement of the glymphatic system in neurodegenerative disease is yet to be fully defined;however, it is becoming increasingly clear that this pathway contributes to parenchymal solute clearance. Importantly, recent data show that proteins prone to intracellular accumulation are subject to glymphatic clearance, suggesting that this system plays a key role in many neurological disorders. In this review, we provide a background on the biology of tau and α-synuclein and discuss the latest findings on the cell-to-cell propagation mechanisms of these proteins. Importantly, we discuss recent data demonstrating that manipulation of the glymphatic system may have the potential to alleviate and reduce pathogenic accumulation of propagation-prone intracellular cytotoxic proteins. furthermore, we will allude to the latest potential therapeutic opportunities targeting the glymphatic system that might have an impact as disease modifiers in neurodegenerative diseases.

关键词： Glymphatic Propagation Tauopathy Synucleinopathy Clearance Aquaporin-4

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Interfacial Charge Transfer in Nanoscale Polymer Transistors

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Nano Research 2008年第4期1卷 341-350页

作者： Jeffrey H.Worne Rajiv Giridharagopal Kevin f.Kelly douglas Natelson Department of Electrical and Computer Engineering Rice University6100 Main St.HoustonTX 77005USA Department of Physics and Astronomy Rice University6100 Main St.HoustonTX 77005USA

Interfacial charge transfer plays an essential role in establishing the relative alignment of the metal fermi level and the energy bands of organic *** the details remain elusive in many systems,this charge transfer has been inferred in a number of photoemission *** present electronic transport measurements in very short channel(Lfrom poly(3-hexylthiophene)(P3HT).As channel length is reduced,the evolution of the contact resistance and the zero gate voltage conductance are consistent with such charge *** channel conduction in devices with Pt contacts is greatly enhanced compared to analogous devices with Au contacts,consistent with charge transfer *** current scanning tunneling microscopy(ACSTM)provides further evidence that holes are transferred from Pt into P3HT,while much less charge transfer takes place at the Au/P3HT interface.

关键词： Organic semiconductors band alignment charge transfer organic field-effect transistor scanning tunneling microscopy

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Materials and technology of Chinese jades dating to the Western Zhou period (1050―771 BCE)

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Science China(Technological Sciences) 2008年第4期51卷 467-480页

作者： Janet G douglas Department of Conservation and Scientific Research Freer Gallery of Art / Arthur M. Sackler Gallery Smithsonian Institution

Excavated jades dating to the Western Zhou period (1050―771 BCE) from the Xi’an area in Shaanxi Province, China, and contemporaneous jades in the collections of the Arthur M. Sackler Gallery at the Smithsonian Institution have been studied to learn about the jade and stone materials and how they were worked during the Western Zhou period. Materials identification was carried out using a combination of techniques such as fourier-transform infrared spectroscopy and X-ray diffraction. Tool marks were studied using stereomicroscopy and examination of mold impressions using scanning electron microscopy. All of these objects were pro- duced through simple processes involving solid drilling, riffling, and sharp point abrasion; and no evidence was found for the use of rotary tools for incising or sawing.

关键词： jade nephrite stone China Western Zhou scanning electron microscopy materials technology tool marks

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Interpreting forest diversity-productivity relationships:volume values,disturbance histories and alternative inferences

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forest Ecosystems 2020年第1期7卷 64-75页

作者： douglas Sheil frans Bongers faculty of Environmental Sciences and Natural Resource Management(MINA) Norwegian University of Life Sciences(NMBU)Box 50031432 AsNorway forest Ecology and forest Management Group Wageningen University&ResearchPO Box 476700 AA WageningenThe Netherlands

Understanding the relationship between stand-level tree diversity and productivity has the potential to inform the science and management of *** shows that plant diversity-productivity relationships are challenging to interpret—and this remains true for the study of forests using non-experimental field *** we highlight pitfalls regarding the analyses and interpretation of such *** examine three themes:1)the nature and measurement of ecological productivity and related values;2)the role of stand history and disturbance in explaining forest characteristics;and 3)the interpretation of any *** show that volume production and true productivity are distinct,and neither is a demonstrated proxy for economic *** stand characteristics,including diversity,volume growth and productivity,vary intrinsically with succession and stand *** should be characterising these relationships rather than ignoring or eliminating *** to do so may lead to misleading *** illustrate,we examine the study which prompted our concerns—Liang et al.(Science 354:aaf8957,2016)—which developed a sophisticated global analysis to infer a worldwide positive effect of biodiversity(tree species richness)on“forest productivity”(stand level wood volume production).Existing data should be able to address many of our *** evaluations will improve understanding.

关键词： Causation Correlation Diversity Inference Productivity Richness Tree-growth Wood-density

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The Effect of Natural Hazard Damage on Manufacturing Value Added and the Impact of Spatiotemporal Data Variations on the Results

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International Journal of Disaster Risk Science 2022年第5期13卷 691-704页

作者： douglas Thomas Jennifer Helgeson National Institute of Standards and Technology GaithersburgMD 20899USA

This study examined the effect of natural hazards on manufacturing industry value added and the sensitivity of the results from changes to spatiotemporal resolution of the *** measured the negative effects of hazards,rather than the net *** models were developed with varying spatio temporal units for the continental United States:annual/county units;annual/state units;and quarterly/state *** simulations were run using each model to estimate the negative effect of damage from all natural hazards on value added across spatiotemporal ***,an investment analysis was conducted to examine the return from public investments in hazard *** results do not demonstrate that,locally,natural hazards reduce value ***,the evidence suggests that natural hazards in the upstream supply chain have statistically significant impact when modeled at the annual/county scale and at the quarterly/state *** local nor supply chain hazards have a statistically significant effect when modeled at the annual/state scale,suggesting that broader spatiotemporal units may obscure the true downstream effects of natural *** investment analysis,utilizing model results,suggests that an investment of USD 100 billion or less is economical if it results in a reduction in losses of 10% or more.

关键词： Manufacturing Natural hazards Spatiotemporal impacts United States Value added

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Slab and Level 2 Automation Design Guidelines for Optimum Metallurgy and Productivity for Plate and Steckel Mills

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Journal of Iron and Steel Research International 2011年第S1期18卷 550-556页

作者： Stalheim douglas DGS Metallurgical Solutions Inc. 15003 NE 10th StreetVancouverWA 98684 USA

Many new steel plate processing facilities have been built in the past 10 years around the world with many more being planned for the *** is especially true in developing countries such as China,India and *** of these facilities are plate mills with either one or two stands or a Steckel mill,typically only one stand designed for the production of structural plate ***,there is a lack of understanding with both the mill builders of the world and the mill owners on the importance of properly matching up the available slab supply (either new as part of a new plate/Steckel mill complex or part of an already existing) with the desired end plate product *** mill builders and owners around the world believe that you can take any slab of any dimension and make any plate dimension you *** this is basically true with today’s Level 2 automation systems,it does not always result in optimum metallurgy/mechanical properties or *** less than optimum condition results in mechanical property failures,shape issues,productivity losses and in general a less than desirable costly processing *** is important to the overall optimization of a steel processing facility that the proper slab dimensions be used to produce the proper final plate dimensions along with achieving the required mechanical *** critical nature of this selection will be dependent on the final plate thickness and overall mechanical property *** mechanical property,shape and overall microstructure are heavily dependent on the ability to properly work the entire cross section of the slab through the rolling *** mechanical property,shape and microstructural issues are a result of improper working of the entire cross section during *** ability for a given mill to properly work the entire cross section is dependent on proper slab selection (total reduction ratio) and a proper rolling schedule either generated manual

关键词： slab dimensions optimization grain size rolling schedule automation Level 2

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