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Therapeutic targets and delivery challenges for Alzheimer's disease

World Journal of Pharmacology 2015年第3期4卷 236-264页

作者： Preshita Desai Harshad Shete Rahul Adnaik john disouza Vandana Patravale Department of Pharmaceutical Sciences and Technology Institute of Chemical Technology Department of Pharmacology Rajarambapu College of Pharmacy Tatyasaheb Kore College of Pharmacy

Dementia, including Alzheimer’s disease, the 21^st Century epidemic, is one of the most signifcant social and health crises which has currently afficted nearly 44 million patients worldwide and about new 7.7 million cases are reported every year. This portrays the unmet need towards better understanding of Alzheimer’s disease pathomechanisms and related research towards more effective treatment strategies. The review thus comprehensively addresses Alzheimer’s disease pathophysiology with an insight of underlying multicascade pathway and elaborates possible therapeutic targets- particularly anti-amyloid approaches, anti-tau approaches, acetylcholinesterase inhibitors, glutamatergic system modifiers, immunotherapy, anti-nflammatory targets, antioxidants, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors and insulin. In spite of extensive research leading to identification of newer targets and potent drugs, complete cure of Alzheimer’s disease appears to be an unreached holy grail. This can be attributed to their ineffective delivery across blood brain barrier and ultimately to the brain. With this understanding, researchers are now focusing on development of drug delivery systems to be delivered via suitable route that can circumvent blood brain barrier effectively with enhanced patient compliance. In this context, we have summarized current drug delivery strategies by oral, transdermal, intravenous, intranasal and other miscellaneous routes and have accentuated the future standpoint towards promising therapy ultimately eading to Alzheimer’s disease cure.

关键词： Neurofbrillary tangles Alzheimer's disease Dementia Amyloid β Tau Neurodegeneration Blood brain barrier Transdermal Nasal

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Challenges and Opportunities in Preserving Key Structural Features of 3D-Printed Metal/Covalent Organic Framework

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Nano-Micro Letters 2024年第8期16卷 362-381页

作者： Ximeng Liu Dan Zhao john Wang Department of Materials Science and Engineering National University of SingaporeSingapore 117574Singapore Department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117585Singapore National University of Singapore(Chongqing)Research Institute Chongqing 401123People’s Republic of China

Metal-organic framework(MOF)and covalent organic framework(COF)are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features,such as large surface area,tunable pore size,and functional surfaces,which have significant values in various application *** emerging 3D printing technology further provides MOF and COFs(M/COFs)with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3D ***,the currently available 3D printing M/COFs strategy faces a major challenge of severe destruction of M/COFs’microstructural features,both during and after 3D *** is envisioned that preserving the microstructure of M/COFs in the 3D-printed monolith will bring a great improvement to the related *** this overview,the 3D-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered *** differences in the properties,applications,and current research states are *** up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3D printing are further discussed for the two types of 3D-printed M/*** the analysis of the current states of 3D-printed M/COFs,the expected future research direction to achieve a highly preserved microstructure in the 3D monolith is proposed.

关键词： Metal-organic frameworks Covalent organic frameworks 3D printing Microstructure Monolith

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Experimental and analytical investigation on friction resistance force between buried coated pressurized steel pipes and soil

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Frontiers of Structural and Civil Engineering 2024年第4期18卷 615-629页

作者： Shaurav ALAM Tanvir MANZUR john MATTHEWS Chris BARTLETT Erez ALLOUCHE Brent KEIL john KRAFT Department of Civil Engineering and Construction Engineering Technology Louisiana Tech UniversityRustonLA 71270USA Department of Civil Engineering Bangladesh University of Engineering and TechnologyDhaka 1000Bangladesh Georgia Tech Research Institute AtlantaGA 30332USA Stantec Inc. Edmonton T5J0K4Canada North West Pipe Company VancouverWA 98684USA

This paper presents an analytical approach for estimating frictional resistance to pipe movement at soil and external pipe surface of buried coated pressurized steel pipes relative to the internal thrust *** proposed analytical method was developed based on 36 experiments,which involved three coating types(cement mortar(CM),polyurethane type-I(PT-I),prefabricated plastic tape(PPT))on pipes’surfaces,three different soils(pea-gravel(PG),sand(S),silty-clay(SC)),and four simulated over burden depths above the pipe’s *** showed frictional resistance decreased with increasing over burden depth above the pipe’s *** degree of frictional resistance at the pipe-soil interface was found to be in the order of PG>SC>S for all coating variations and overburden *** coated pipe buried in all three types of soil produced significantly higher frictional resistance as compared to other coating *** on experimental data,the developed analytical introduced a dimensionless factor“Z”,which included effects of types of coatings,soil,and overburden depths for simplified rapid *** showed that the method provided a better prediction of frictional resistance forces,in comparison to previous analytical methods,which were barely close in predicting friction resistance for different coating variations,soil types,and overburden *** resistance force values reported herein could be considered conservative.

关键词： friction resistance force thrust force coated pressurized steel pipe soil type overburden depth

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A Population Dynamics Approach to the Distribution of Space Debris in Low Earth Orbit

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Communications on Applied Mathematics and Computation 2024年第1期6卷 340-353页

作者： john Jurkiewicz Peter Hinow Department of Mathematical Sciences University of Wisconsin-MilwaukeeMilwaukeeWI53201USA

The presence of the debris in the Earth’s orbit poses a significant risk to human activity in outer *** debris population continues to grow due to ground launches,the loss of external parts from space ships,and uncontrollable collisions between objects.A computationally feasible continuum model for the growth of the debris population and its spatial distribution is therefore *** we propose a diffusion-collision model for the evolution of the debris density in the low-Earth orbit and its dependence on the ground-launch *** parametrize this model and test it against data from publicly available object catalogs to examine timescales for the uncontrolled ***,we consider sensible launch policies and cleanup strategies and how they reduce the future risk of collisions with active satellites or space ships.

关键词： Population dynamics Space debris Kessler syndrome Diffusion Low-Earth orbit

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Surgical treatment of inflammatory bowel disease:From the gastroenterologist’s stand-point

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1235-1254页

作者： john K Triantafillidis Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece Hellenic Society of Gastrointestinal Oncology Haidari 12461AthensGreece

Treatment of ulcerative colitis(UC)and Crohn’s disease(CD)represents,in the majority of cases,a real challenge to the gastroenterologist’s abilities and skills as well as a clinical test concerning his/her levels of medical knowledge and *** the last two decades,our pharmaceutical arsenal was significantly strengthened,especially after the introduction of the so-called biological agents,drugs which to a large extent not only improved the results of conservative treatment but also changed the natural history of the ***,colectomy is still necessary for some patients with severe UC although smaller compared to the past,precisely because of the improvements achieved in the available conservative ***,surgeries to treat colon dysplasia and cancer are increasing to some *** the same time,satisfactory improvements in surgical techniques,the pre-and post-operative care of patients,as well as the selection of the appropriate time for performing the surgery have been *** patients with CD,the improvement of conservative treatment did not significantly change the need for surgical treatment since two-thirds of patients need to undergo surgery at some point in the course of their *** the other hand,the outcome of the operation has improved through good preoperative care as well as the wide application of more conservative surgical techniques aimed at keeping as much of the bowel in situ as *** article discusses the indications for surgical management of UC patients from the gastroenterologist’s point of view,the results of the emerging new techniques such as transanal surgery and robotics,as well as alternative operations to the classic ileo-anal-pouch *** author also discusses the basic principles of surgical management of patients with CD based on the results of the relevant *** self-evident is emphasized,that is,to achieve an excellent therapeutic result in patients with se

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Surgery Treatment Ileo-anal-pouch anastomosis Indications Techniques

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Study of hybrid nanofluid flow in a stationary cone-disk system with temperature-dependent fluid properties

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Applied Mathematics and Mechanics(English Edition) 2024年第4期45卷 677-694页

作者： A.S.john B.MAHANTHESH G.LORENZINI Center for Mathematical Needs Department of MathematicsCHRIST(Deemed to be University)Karnataka 560029India School of Mathematical and Statistical Sciences The University of Texas Rio Grande ValleyTexas 78539U.S.A. Department of Engineering and Architecture University of ParmaParma 43124Italy

Cone-disk systems find frequent use such as conical diffusers,medical devices,various rheometric,and viscosimetry *** this study,we investigate the three-dimensional flow of a water-based Ag-Mg O hybrid nanofluid in a static cone-disk system while considering temperature-dependent fluid *** the variable fluid properties affect the dynamics and heat transfer features is studied by Reynolds's linearized model for variable viscosity and Chiam's model for variable thermal *** single-phase nanofluid model is utilized to describe convective heat transfer in hybrid nanofluids,incorporating the experimental *** model is developed as a coupled system of convective-diffusion equations,encompassing the conservation of momentum and the conservation of thermal energy,in conjunction with an incompressibility condition.A self-similar model is developed by the Lie-group scaling transformations,and the subsequent self-similar equations are then solved *** influence of variable fluid parameters on both swirling and non-swirling flow cases is ***,the Nusselt number for the disk surface is *** is found that an increase in the temperature-dependent viscosity parameter enhances heat transfer characteristics in the static cone-disk system,while the thermal conductivity parameter has the opposite effect.

关键词： hybrid nanofluid cone-disk system laminar flow variable fluid property Nusselt number

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Does photobiomodulation require glucose to work effectively?

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Neural Regeneration Research 2024年第5期19卷 945-946页

作者： Jaimie Hoh Kam john Mitrofanis UniversitéGrenoble Alpes Fonds de Dotation ClinatecGrenobleFrance University College London Institute of OphthalmologyUK

A main requirement for cells to function normally is the availability of ***,available either direct from circulation or storage,is converted to the essential energy that cells need to drive critical intrinsic *** cells are deprived of glucose,they become dysfunctional and suffer ***,the use of specific wavelengths of light on body tissues,has been shown to promote,through small organelles called mitochondria,the metabolism of glucose to make energy for cells;this energy can be used to improve cell function and *** this perspective,we hypothesize that the availability of glucose is central to the core mechanism of photobiomodulation;that photobiomodulation is at its most efficient in stimulating mitochondrial activity and improving cell function when there is glucose readily available.

关键词： metabolism distress stimulating

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A poetics of“Wind in a Box”

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Language and Semiotic Studies 2024年第3期10卷 408-414页

作者： john Robinson West Virginia Department of Education CharlestonUSA

This essay is a re-application of the language codes of Roland Barthes and Jonathan Culler’s concept for Structuralist *** approach I use explores the codes demonstrated in Barthes’well-known text,S/Z with slight modifications for their application to *** concepts borrowed from *** are from his book of the same title:Structuralist Poetics:Structuralism,Linguistics and the Study of Literature(Cornell University Press,1975).Culler’s main argument is that there must be other,un-attempted strategies combined with conventional approaches in literature of that time *** answer to this problem was to develop a set of linguistic-based concepts to compensate for the reader in the analysis of literary works.I have applied in this essay my approach based on Culler’s methodology and the language codes of Roland Barthes:semantic,symbolic,cultural-referential,actional and hermeneutic.I apply Culler’s concepts to a reading of poetry followed by an application of the language codes as a further development of my work in revitalizing this never-before applied method.

关键词： poetics literary theory poetry

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Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron Bell Ottawa Hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

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Stable hydrogen isoscape in precipitation generated using data fusion for East China

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Science China Earth Sciences 2024年第9期67卷 2972-2988页

作者： Jiacheng CHEN Jie CHEN Xunchang john ZHANG Peiyi PENG State Key Laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan 430072China Hubei Key Laboratory of Water System Science for Sponge City Construction Wuhan UniversityWuhan 430072China USDA-ARS Oklahoma and Central Plains Agricultural Research Center El Reno OK 73036USA Southwest Research Institute for Hydraulic and Water Transport Engineering Chongqing Jiaotong UniversityChongqing 400016China

The stable hydrogen isotope in precipitation is an effective environmental tracer for climatic and hydrologic ***,accurate and high-precision precipitation hydrogen isoscapes are currently unavailable in *** this study,a data fusion method based on Convolutional Neural Networks(CNN)is used to fuse the hydrogen isotopic composition(δ^(2)H_(p))of observations and isotope-equipped general circulation model(iGCM)simulations.A precipitation hydrogen isoscape with a temporal resolution of monthly and a spatial resolution of 50-60 km is established for East China for the 1969-2017 *** to building the isoscape,the performance of three data fusion methods(DFMs)and two bias correction methods(BCMs)is *** results indicate that the CNN fusion method performs the best with a correlation coefficient larger than 0.90 and root mean square error smaller than 10.5‰ when using observation as a *** fusion methods based on back propagation and long short-term memory neural network perform similarly,while slightly outperforming the bias correction ***,the CNN method is used to generate the hydrogen isoscape,and the temporal and spatial distribution characteristics of the hydrogen isotope in precipitation are analyzed based on this *** generated isoscape shows similar spatial and temporal distribution characteristics to *** general,the distribution pattern of δ^(2)H_(p) is consistent with the temperature effect in northern China,and consistent with the precipitation amount effect in southern *** trend of the δ^(2)H_(p) time series is consistent with that of observed precipitation and ***,the generated isoscape effectively reproduces the observations,and has the characteristics of time continuity and relative spatial regularity,which can provide valuable data support for tracking atmospheric and hydrological processes.

关键词： Precipitation Precipitation isotope General circulation model Data fusion Dataset

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