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The concept of gene therapy for glaucoma:the dream that has not come true yet

Neural Regeneration Research 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu adrian.Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland glaucoTech co. KatowicePoland

gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,crry,c3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,cOX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Single-atom catalysts for the electrochemical reduction of carbon dioxide into hydrocarbons and oxygenates

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carbon Energy 2024年第3期6卷 64-117页

作者： Karl adrian.gandionco Juwon Kim Lieven Bekaert Annick Hubin Jongwoo Lim Department of chemistry Seoul National UniversitySeoulRepublic of Korea Research group Electrochemical and Surface Engineering(SURF) Department of Materials and ChemistryVrije Universiteit BrusselBrusselsBelgium

The electrochemical reduction of carbon dioxide offers a sound and economically viable technology for the electrification and decarbonization of the chemical and fuel *** this technology,an electrocatalytic material and renewable energy-generated electricity drive the conversion of carbon dioxide into high-value chemicals and carbon-neutral *** the past few years,single-atom catalysts have been intensively studied as they could provide near-unity atom utilization and unique catalytic ***-atom catalysts have become one of the state-of-the-art catalyst materials for the electrochemical reduction of carbon dioxide into carbon ***,it remains a challenge for single-atom catalysts to facilitate the efficient conversion of carbon dioxide into products beyond carbon *** this review,we summarize and present important findings and critical insights from studies on the electrochemical carbon dioxide reduction reaction into hydrocarbons and oxygenates using single-atom *** is hoped that this review gives a thorough recapitulation and analysis of the science behind the catalysis of carbon dioxide into more reduced products through singleatom catalysts so that it can be a guide for future research and development on catalysts with industry-ready performance for the electrochemical reduction of carbon dioxide into high-value chemicals and carbon-neutral fuels.

关键词： electrocatalysis electrochemical cO_(2)reduction hydrocarbons oxygenates single-atom catalysts

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A Distributionally Robust Optimization Scheduling Model for Regional Integrated Energy Systems considering Hot Dry Rock co-generation

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computer Modeling in Engineering & Sciences 2024年第8期140卷 1387-1404页

作者： Hao Qi Mohamed Sharaf Andres Annuk adrian.Ilinca Mohamed A.Mohamed college of Electrical and New Energy China Three Gorges UniversityYichang443002China Department of Industrial Engineering College of EngineeringKing Saud UniversityRiyadh11421Saudi Arabia Institute of Forestry and Engineering Estonian University of Life SciencesTartu51006Estonia Department of Mechanical Engineering école de Technologie SupérieureMontréalQC H3C 1K3Canada Electrical Engineering Department Faculty of EngineeringMinia UniversityMinia61519Egypt

Hot dry rock(HDR)is rich in reserve,widely distributed,green,low-carbon,and has broad development potential and *** this paper,a distributionally robust optimization(DRO)scheduling model for a regionally integrated energy system(RIES)considering HDR co-generation is ***,the HDR-enhanced geothermal system(HDR-EgS)is introduced into the ***-EgS realizes the thermoelectric decoupling of combined heat and power(cHP)through coordinated operation with the regional power grid and the regional heat grid,which enhances the system wind power(WP)feed-in ***,peak-hour loads are shifted using price demand response guidance in the context of time-of-day ***,the optimization objective is established to minimize the total cost in the RIES scheduling cycle and construct a DRO scheduling model for RIES with *** simulating a real small-scale RIES,the results show that HDR-EgS can effectively promote WP consumption and reduce the operating cost of the system.

关键词： Energy harvesting integrated energy systems optimum scheduling time-of-use pricing demand response geothermal energy

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Advanced wind turbine blade inspection with hyperspectral imaging and 3D convolutional neural networks for damage detection

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Energy and AI 2024年第2期16卷 528-537页

作者： Patrick Rizk Frederic Rizk Sasan Sattarpanah Karganroudi adrian.Ilinca Rafic Younes Jihan Khoder Department of Mechanical Engineering Universitédu QuébecàTrois-RivièresDrummondvilleQCCanada centre national intégrédu manufacturier intelligent(cNIMI) Universitédu QuébecàTrois-RivièresDrummondvilleQCCanada Department of Mathematics Computer Science and EngineeringUniversitédu QuébecàRimouski300 allée des UrsulinesRimouskiQCG5L3A1Canada The center for Advanced computer Studies University of Louisiana at LafayetteLafayetteLAUSA T3E Industrial Research group Mechanical Engineering DepartmentÉcole de Technologie Supérieure1100 Notre-Dame St WMontréalQC H3C 1K3Canada Faculty of Engineering Third BranchLebanese UniversityHadathBeirutLebanon LISV Laboratory University of Versailles Saint-Quentin-en-Yvelines10-12 Avenue de l'Europe78140VélizyFrance

In the context of global efforts to mitigate climate change by pursuing sustainable energy sources, wind energy has emerged as a critical contributor. However, the wind energy industry faces substantial challenges in maintaining and preserving the integrity of wind turbine blades. Timely and accurate detection and classification of blade faults, encompassing issues such as cracks, erosion, and ice buildup, are imperative to uphold wind turbines' ongoing efficiency and safety. This study introduces an inventive approach that amalgamates hyperspectral imaging and 3D convolutional Neural Networks (cNNs) to augment the precision and efficiency of wind turbine blade fault detection and classification. Hyperspectral imaging is harnessed to capture comprehensive spectral information from blade surfaces, facilitating exact fault identification. The process is streamlined through Incremental Principal component Analysis (IPcA), reducing data dimensions while maintaining integrity. The 3D cNN model demonstrates remarkable performance, achieving high accuracy in detecting all fault categories in full-band hyperspectral images. The model retains high accuracy even with dimensionality reduction to 20 spectral bands. The reduced processing time of the 20-band image enhances the practicality of real-world applications, thereby reducing downtime and maintenance expenditures. This research represents a significant advancement in wind turbine blade inspection, contributing to the sustainability and dependability of wind energy systems and furthering the cause of a cleaner and more sustainable energy future as part of the broader fight against climate change.

关键词： blade thereby turbine

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.adrian.Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Testing discrete symmetries at a super τ-charm factory

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Frontiers of physics 2016年第1期11卷 17-25页

作者： adrian.John Bevan Particle Physics Research centre Queen Mary University of London Mile End Road London E1 4NS UK

Tests of discrete symmetry violation have played an important role in understanding the structure of weak interactions in the Standard Model of particle physics. Historically, these measurements have been extensively performed in experiments with large samples of K and B mesons. A high luminosity τ-charm facility presents physicists with the opportunity to comprehensively explore discrete symmetry violation and test the Standard Model using τ leptons, charm mesons, and charmed baryons. This paper discusses several possible measurements for a future T-charm factory.

关键词： discrete symmetries P c T cP cPT violation

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Exon-centric regulation of pyruvate kinase M alternative splicing via mutually exclusive exons

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分子细胞生物学报:英文版 2012年第2期4卷 79-87页

作者： Zhenxun Wang Deblina chatterjee Hyun Yong Jeon Martin Akerman Matthew g.Vander Heiden Lewis c.cantley adrian.R.Krainer cold Spring Harbor Laboratory PO Box 100Cold Spring HarborNY 11724USA Watson School of Biological Sciences Cold Spring HarborNY 11724USA graduate Program in Molecular and cellular Biology Stony Brook UniversityStony BrookNY 11794USA Koch Institute for Integrative cancer Research at MIT CambridgeMA 02139USA Division of Signal Transduction Beth Israel Deaconess Medical Center and Department of Systems BiologyHarvard Medical SchoolBostonMA 02115USA

Alternative splicing of the pyruvate kinase M gene(PK-M)can generate the M2 isoform and promote aerobic glycolysis and tumor ***,the cancer-specific alternative splicing regulation of PK-M is not completely ***,we demonstrate that PK-M is regulated by reciprocal effects on the mutually exclusive exons 9 and 10,such that exon 9 is repressed and exon 10 is activated in cancer ***,exonic,rather than intronic,cis-elements are key determinants of PK-M splicing isoform *** a systematic sub-exonic duplication approach,we identify a potent exonic splicing enhancer in exon 10,which differs from its homologous counterpart in exon 9 by only two *** identify SRSF3 as one of the cognate factors,and show that this serine/arginine-rich protein activates exon 10 and mediates changes in glucose *** findings provide mechanistic insights into the complex regulation of alternative splicing of a key regulator of the Warburg effect,and also have implications for other genes with a similar pattern of alternative splicing.

关键词： alternative splicing cancer metabolism pyruvate kinase SRSF3

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A soil quality index for evaluation of degradation under land use and soil erosion categories in a small mountainous catchment, Iran

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Journal of Mountain Science 2019年第11期16卷 2577-2590页

作者： Kazem NOSRATI adrian.LcOLLINS Department of Physical geography School of Earth SciencesShahid Beheshti University*** TehranIran Sustainable Agriculture Sciences Department Rothamsted ResearchNorth WykeOkehamptonEX202SBUK

Soil erosion and land use type have long been viewed as being particularly important drivers of soil *** objectives of this study,therefore,were to select a new soil quality index(SQI)which varies significantly with land use/soil erosion,and to evaluate the new SQI using expert *** total,18 soil physical,chemical,and biochemical properties(indicators)were measured on 56 soil samples collected from four land use/soil erosion categories(rangeland/surface erosion,rangeland/subsurface erosion,cultivated land/surface erosion and dry-farming land/surface erosion).Principal component and classification analysis(PccA)identified five Pcs that explained 77.7%of the variation in soil properties with the biochemical Pc varying significantly with land use/soil *** discriminant analysis(gDA)selected urease and clay as the most sensitive properties distinguishing the land use/soil erosion *** gDA canonical scores for the new SQI were significantly correlated with expert opinion soil surface summed scores(for soil movement,surface litter,pedestalling,rills and flow pattern)derived using the *** of the Interior Bureau of Land Management(BLM)method.A forward stepwise general regression model revealed that the new SQI values were explained by soil movement,surface litter,and the summed values of the soil surface ***,this study confirmed that soil quality in the study area in Iran is controlled by land use and corresponding soil erosion.

关键词： Soil quality index Land use Erosion status Soil enzyme activities Multivariate statistical techniques

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Assessment of the role of slit as a safety valve in failure of levees

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International Journal of Sediment Research 2008年第4期23卷 361-375页

作者： c.S.P.OJHA V.P.SINgH D.D.adrian Department of civil Engineering Indian Institute of TechnologyRoorkee Uttaranchal 247667 IndiaProf. caroline and William N. Lehrer Distinguished chair in Water Engineering Professor of Civil & Environmental Engineering and Professor of Biological and Agricultural Engineering Texas A & M University2117 TAMU Dept. of Biological & Agric. Engineering 321 Scoates Hall College Station Texas 77843-2117 USA Department of civil and Environmental Engineering Louisiana State UniversityBaton Rouge LA 70803-6405 U. S. A.Rubicon Professor

The development of a narrow channel or slit due to piping just underneath the base of levees channel has been reported to be useful to withstand the increase in the head beyond critical head conditions. Also, the maximum slit length has been emphasized to be up to half of the base width. By developing a model of critical head considering slit, it is found that the critical head can increase with the development of slit length only under certain conditions. Analysis of piping failure data indicates that the critical head expressions considering slit length constitute a potentially useful model for critical head.

关键词： Failure of levee Piping Flood defense Water head seepage erosion

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Habitat use in eight populations of Sceloporus grammicus(Squamata:Phrynosomatidae)from the Mexican Plateau

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Integrative Zoology 2017年第3期12卷 198-210页

作者： adrian.LEYTE-MANRIQUE Uriel HERNÁNDEZ-SALINAS Aurelio RAMÍREZ-BAUTISTA Vicente MATA-SILVA Jonathon c.MARSHALL Laboratorio de Biología Instituto Tecnológico Superior de SalvatierraSalvatierraGuanajuatoMexico Instituto Politécnico Nacional CIIDIR Unidad DurangoSigma 119Fraccionamiento 20 de Noviembre IIDurangoDurango 34220México Laboratorio de Ecología de Poblaciones Centro de Investigaciones BiológicasUniversidad Autónoma del Estado de HidalgoKm 4.5 carretera Pachuca-Tulancingo42184Mineral de la ReformaHidalgoMexico Department of Biological Sciences The University of Texas at El PasoEl PasoTexasUSA Department of Zoology Weber State University1415 Edvalson StreetOgdenUtahUSA

Studies on habitat use have often helped explain observed variation in morphology,behavior and reproductive characteristics among populations within a single *** we analyze morphological and ecological characteristics of individuals from the Sceloporus grammicus species complex from 7 different localities(cER,El cerezo;PAc,Pachuca;HUI,Huichapan;EZA,Emiliano Zapata;SMR,San Miguel Regla;LMJ,La Mojonera;and LMZ,La Manzana)in the state of Hidalgo,and one locality(cahuacán)in the State of Mexico.A canonical correspondence analysis(ccA)showed that females from PAc,EZA,LMZ,HUI,SMR and cAH populations use similar microhabitats characterized mostly by bare soil,in females from LMJ and cER use microhabitats characterized primarily by vegetation and *** were observed using 12 different types of *** regard to perch height use,the ccA showed that females from PAc,LMJ,LMZ,SMR,cER and cAH populations were correlated with height to nearest perch(HNP),in the rest of the females were not related to any perch use *** contrast,the ccA showed that males from PAc,LMJ and cAH were characterized by microhabitats with higher vegetal coverage,while males from LMZ and cER used microhabitats composed of bare soil,but males from HUI and SMR populations used microhabitats composed chiefly of bare soil and *** respect to perch height use,the ccA showed that males from PAc,LMJ,EZA and LMZ were correlated with distance to the nearest perch,but the rest of the males were not correlated with any perch use *** were observed in 9 different perch *** males were larger than the females in all morphological variables ***,in both sexes the snout-vent length is positively correlated with all morphological variables,and although both the slope and ordinate of the origin of all morphological variables were larger in males than females,the analysis of covariance indicated that there is no increase in the morphological variables with inc

关键词： canonical correspondence analyses habitat use morphology populations Sceloporus grammicus

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