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Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds

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Bioactive Materials 2022年第3期7卷 358-372页

作者： Chia-Chen Hsu Julian H.George Sharlayne Waller Cyril Besnard david a nagel Eric J Hill Michael D.Coleman Alexander M.Korsunsky Zhanfeng Cui Hua Ye Institute of Biomedical Engineering Department of Engineering ScienceUniversity of OxfordOX37DQUK MBLEM Department of Engineering ScienceUniversity of OxfordParks RoadOxfordOX13PJUK School of Biosciences College of Health and Life SciencesAston UniversityBirminghamB47ETUK Translational Medicine Research Group Aston Medical SchoolCollege of Health and Life SciencesAston UniversityBirminghamB47ETUK

To reflect human development,it is critical to create a substrate that can support long-term cell survival,differentiation,and maturation.Hydrogels are promising materials for 3D cultures.However,a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction.Herein,granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell(hiPSC)-derived neural networks.A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules.Cells and hydrogel granules were combined using a weaker secondary gelation step,forming self-supporting cell laden scaffolds.At three and seven days,granular scaffolds supported higher cell viability compared to bulk hydrogels,whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions(65.52±11.59μm)after seven days compared to bulk hydrogels(22.90±4.70μm).Long-term(three-month)cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold.This approach is significant as it provides a simple,rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

关键词： Microgel Hydrogel Hyaluronan iPSC Neural tissue engineering 3D printing

智能手机，将会成为未来市场的霸主 PalmSource总裁兼CEO david nagel对话《IT时代周刊》

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IT时代周刊 2005年第10期15卷 34-35页

作者：许萍 david nagel PalmSource

2005年，智能手机大放光彩，中国手机市场成为各跨国公司决战的战场，纷纷投入重兵，决意从这个新兴手机市场上分到一份巨大的蛋糕。

关键词：智能手机 david CEO IT 手机市场 2005年跨国公司

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多重挑战时期的货币政策

中国金融 2024年第4期 32-33页

作者：约阿希姆·内格尔芦国荣(译) 德意志联邦银行中国人民银行甘肃省分行

最重要的挑战仍是过高的通胀率在欧元体系货币政策面临的多重挑战中,最重要的就是欧元区通胀率在过长的时期内持续运行在较高水平,为此,欧洲中央银行通过连续加息、缩减中央银行资产负债表等货币政策措施来稳定价格和预期。

关键词：欧洲中央银行欧元区通胀率货币政策加息中央银行资产负债表多重挑战欧元体系

Efficacy and safety of bridging thrombolysis initiated before transfer in a drip-and-ship stroke service

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Stroke & Vascular Neurology 2022年第1期7卷 22-28页

作者： Jan Christoph Purrucker Miriam Heyse Simon nagel Christoph Gumbinger Fatih Seker Markus Mohlenbruch Peter Arthur Ringleb Department of Neurology Heidelberg University HospitalHeidelbergBaden-WürttembergGermany Department of Neuroradiology Heidelberg University HospitalHeidelbergBaden-WürttembergGermany

Objective Data regarding the efficacy and safety of bridging thrombolysis(BT)initiated before transfer for evaluation of endovascular therapy is heterogeneous.We,therefore,analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service.Methods Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions(LVO)transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017–2020 were identified from a local prospective stroke database and categorised according to BT and no-BT.BT was defined as intravenous thrombolysis initiated before transfer.LVO was assessed before and after transfer.Functional outcome before stroke and at 3 months using the modified Rankin scale(mRS)was determined.Excellent outcome was defined as mRS 0–1 or return to prestroke mRS.For safety analysis,intracranial haemorrhages and mortality at 3 months were analysed.Main analysis was limited to patients with anterior circulation stroke.Results Of N=714 patients,n=394(55.2%)received BT.More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy(n=46,11.7%)than patients who did not receive BT before transfer(n=4,1.3%,p<0.001).In multivariate analysis,BT was the strongest independent predictor of early recanalisation(adjusted OR 10.9,95%CI 3.8 to 31.1,p<0.001).BT tended to be an independent predictor of an excellent outcome at 3 months(adjusted OR 1.38,95%CI 0.97 to 1.96,p=0.077).There were no differences in safety between the BT and no-BT groups.Conclusions BT initiated before transfer was a strong independent predictor of early recanalisation.

关键词： drip initiated service

Visual function restoration with a highly sensitive and fast Channelrhodopsin in blind mice

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1389-1391页

作者： Fei Chen Xiaodong Duan Yao Yu Shang Yang Yuanyuan Chen Christine EGee Georg nagel Kang Zhang Shiqiang Gao Yin Shen Eye Center Wuhan University Renmin HospitalWuhanChina Department of Neurophysiology Institute of PhysiologyBiocenterUniversity of WuerzburgWuerzburgGermany Institute for Synaptic Physiology University Medical Center Hamburg EppendorfHamburgGermany Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and Technology and University HospitalMacaoChina Frontier Science Center for Immunology and Metabolism and Medical Research Institute at School of MedicineWuhan UniversityWuhanChina

Inherited and age-related retinal degenerative diseases cause progressive loss of photoreceptors,ultimately leading to blindness.Optogenetics is a promising strategy for restoring visual function through photosensitive proteins’ectopic expression in surviving retinal neurons.1 Very recently,the optogenetic method with a red-shifted Channelrhodopsin was clinically applied for partial recovery of visual function in a blind patient.2 However,major obstacles to achieving optimal optogenetic vision restoration are either the low light sensitivity or the slow kinetics of existing rhodopsin-based optogenetic tools,which can be improved by molecular engineering to enhance the efficacy of fast Channelrhodopsins(ChRs).

关键词： Visual visual function

Lessons Learned and Future Challenges for Integrated and Participatory Approaches to Mountain Research——Conclusions from the Mountain Symposium and this Special Issue

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Journal of Mountain Science 2006年第4期3卷 347-354页

作者： Franz Heidhues Karl Stahr Uwe Jens nagel david Thomas Andreas Neef University of Hohenheim Stuttgart Germany Humboldt University Berlin Germany World Agroforestry Center Chiang Mai Thailand

The International Symposium 'Towards Sustainable Livelihoods and Ecosystems in Mountainous Regions', held in Chiang Mai from 7-9 March 2006 (hereafter referred to as 'Mountain Symposium'),brought together a wealth of experience from mountain research and development in four continents. Some of its highlights are presented in this Special Issue.

关键词：山区开发国际研讨会专刊可持续民生可持续生态系统综合研究分担研究

Quantifying the effect of persistent dryer climates on forest productivity and implications for forest planning:a case study in northern Germany

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Forest Ecosystems 2018年第4期5卷 451-471页

作者： Matthias Albert Ralf-Volker nagel Johannes Sutmoller Matthias Schmidt Department of Forest Growth Northwest German Forest Research Institute GottingenGermany Department of Environmental Control Northwest German Forest Research InstituteGottingenGermany.

Background: Forest management decisions are based on expectations of future developments. For sound decisions it is essential to accurately predict the expected values in future developments and to account for their inherent uncertainty,for example the impact of climate change on forests. Changing climatic conditions affect forest productivity and alter the risk profile of forests and forest enterprises. Intensifying drought stress is seen as one major risk factor threatening forest management in the north German lowlands. Drought stress reduces tree growth and vitality and might even trigger mortality. But so far, it is not possible to quantify effects of a persistent dryer climate on forest productivity at a level suitable for forest management.Methods: We apply a well-established single-tree forest growth simulator to quantify the effect of persistent dryer climates on future forest productivity. We analyse the growth of Scots pine(Pinus sylvestris L.), European beech(Fagus sylvatico L.) and oak(Quercus robur L. and Quercus petraea(Matt.) Liebl.) in two forest regions in the north German lowlands for a time interval of 60 years until 2070. The growth response under three different climate projections is compared to a baseline scenario.Results: The results show clear differences in volume increment to persistent dryer climates between tree species. The findings exhibit regional differences and temporal trends. While mean annual increment at biological rotation age of Scots pine and oak predominantly benefits from the projected climate conditions until 2070, beech might suffer losses of up to 3 m^3·ha^(-1)yr^(-1) depending on climate scenario and region. However, in the projection period2051 to 2070 the uncertainty ranges comprise positive as well as negative climatic effects for all species.Conclusions: The projected changes in forest growth serve as quantitative contributions to provide decision support in the evaluation of, for example, species future site suitability and timber supply assessments. The analys

关键词： Climate change Forest growth Forest productivity Persistent dryer climate simulation study Uncertainty

Hydro-mechanical fault reactivation modeling based on elasto-plasticity with embedded weakness planes

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第4期12卷 877-885页

作者： Luca Urpi Bastian Graupner Wenqing Wang Thomas nagel Antonio PRinaldi Swiss Seismological Service Swiss Federal Institute of TechnologyETH ZürichZürichSwitzerland Swiss Federal Nuclear Safety Inspectorate ENSI BruggSwitzerland Department of Environmental Informatics Helmholtz Centre for Environmental ResearcheUFZLeipzigGermany Technische Universitat Bergakademie Freiberg FreibergGermany

In this paper,an elasto-plastic constitutive model is employed to capture the shear failure that may occur in a rock mass presenting mechanical discontinuities,such as faults,fractures,bedding planes or other planar weak structures.The failure may occur in two modes:a sliding failure on the weak plane or an intrinsic failure of the rock mass.The rock matrix is expected to behave elastically or fail in a brittle manner,being represented by a non-associated Mohr-Coulomb behavior,while the sliding failure is represented by the evaluation of the Coulomb criterion on an explicitly defined plane.Failure may furthermore affect the hydraulic properties of the rock mass:the shearing of the weakness plane may create a transmissive fluid pathway.Verification of the mechanical submodel is conducted by comparison with an analytical solution,while the coupled hydro-mechanical behavior is validated with field data and will be applied within a model and code validation initiative.The work presented here aims at documenting the progress in code development,while accurate match of the field data with the numerical results is current work in progress.

关键词： Fault reactivation Plane of weakness Finite element Argillaceous material Clay Permeability

Assessing risks and uncertainties in forest dynamics under different management scenarios and climate change

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Forest Ecosystems 2015年第3期2卷 169-189页

作者： Matthias Albert Jan Hansen Jürgen nagel Matthias Schmidt Hermann Spellmann Northwest German Forest Research Station

Background: Forest management faces a climate induced shift in growth potential and increasing current and emerging new risks. Vulnerability analysis provides decision support based on projections of natural resources taking risks and uncertainties into account. In this paper we(1) characterize differences in forest dynamics under three management scenarios,(2) analyse the effects of the three scenarios on two risk factors, windthrow and drought stress, and(3) quantify the effects and the amount of uncertainty arising from climate projections on height increment and drought stress.Methods: In four regions in northern Germany, we apply three contrasting management scenarios and project forest development under climate change until 2070. Three climate runs(minimum, median, maximum) based on the emission scenario RCP 8.5 control the site-sensitive forest growth functions. The minimum and maximum climate run define the range of prospective climate development.Results: The projections of different management regimes until 2070 show the diverging medium-term effects of thinnings and harvests and long-term effects of species conversion on a regional scale. Examples of windthrow vulnerability and drought stress reveal how adaptation measures depend on the applied management path and the decision-maker’s risk attitude. Uncertainty analysis shows the increasing variability of drought risk projections with time. The effect of climate projections on height growth are quantified and uncertainty analysis reveals that height growth of young trees is dominated by the age-trend whereas the climate signal in height increment of older trees is decisive.Conclusions: Drought risk is a serious issue in the eastern regions independent of the applied silvicultural scenario,but adaptation measures are limited as the proportion of the most drought tolerant species Scots pine is already high. Windthrow risk is no serious overall threat in any region, but adequate counter-measures such as species conversion, species mixture or reduction of

关键词： Climate change Silvicultural management strategies