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Effects of P301l-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al kabbani Christoph köhler hans Zempel Institute of human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301l)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301l-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301l-TAU in human MAPT-kO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301l-TAU(p R5 mice).human neurons expressing the longest TAU isoform(2N4R)with the P301l mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301l-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301l-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301l-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301l pR5 mice TAU tauopathy tubulin code

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina hromada Patrick heimel Markus kerbl lászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes C.heinzel Antal Nógrádi Andreas h.Teuschl-Woller David hercher Department life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). however, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Alternative Approach to the Optimality of the Threshold Strategy for Spectrally Negative lvy Processes

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Acta Mathematicae Applicatae Sinica 2013年第4期29卷 705-716页

作者： Ying ShEN Chuan-cun YIN kam Chuen yuen School of Mathematical Sciences Qufu Normal UniversityChina Department of Statistics and Actuarial Science The University of Hong Kong

Consider the optimal dividend problem for an insurance company whose uncontrolled surplus precess evolves as a spectrally negative levy process. We assume that dividends are paid to the shareholders according to admissible strategies whose dividend rate is bounded by a constant. The objective is to find a dividend policy so as to maximize the expected discounted value of dividends which are paid to the shareholders until the company is ruined. In this paper, we show that a threshold strategy （also called refraction strategy） forms an optimal strategy under the condition that the levy measure has a completely monotone density.

关键词： Spectrally negative levy process optimal dividend problem scale function complete monotonic-ity threshold strategy

Multiple sclerosis is at a checkpoint: advancing the program

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Neural Regeneration Research 2025年第3期20卷 811-812页

作者： Brandon C.Smith Jessica l.Williams Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Biological Geologicaland Environmental SciencesCleveland State UniversityClevelandOHUSA

Multiple sclerosis(MS) is a chronic inflammatory and demyelinating disease of the central nervous system(CNS). Patients with MS experience sensory and motor function loss due to myelin and/or axon damage perpetuated b... 详细信息

关键词： hauser sclerosis damage

Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael J.lee Ryota l.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

Force and impulse multi-sensor based on flexible gate dielectric field effect transistor

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 214-220页

作者： Chao Tan Junling lü Chunchi Zhang Dong liang lei Yang Zegao Wang College of Materials Science and Engineering Sichuan UniversityChengdu 610065China The 54th Research Institute of China Electronics Technology Group Corporation Shijiazhuang 050081China

Nowadays,force sensors play an important role in industrial production,electronic information,medical health,and many other ***-dimensional material-based filed effect transistor(2D-FET)sensors are competitive with nano-level size,lower power consumption,and accurate ***,few of them has the capability of impulse detection which is a path function,expressing the cumulative effect of the force on the particle over a period of *** we fabricated the flexible polymethyl methacrylate(PMMA)gate dielectric MoS_(2)-FET for force and impulse sensor *** systematically investigated the responses of the sensor to constant force and varying forces,and achieved the conversion factors of the drain current signals(I_(ds))to the detected impulse(I).The applied force was detected and recorded by I_(ds)with a low power consumption of~30 *** sensitivity of the device can reach~8000%and the 4×1 sensor array is able to detect and locate the normal force applied on ***,there was almost no performance loss for the device as left in the air for two months.

关键词： flexible gate dielectric transistor force sensor impulse sensor force sensor array

Viscosity and structure relationship with equimolar substitution of CaO with MgO in the CaO–MgO–Al_(2)O_(3)–SiO_(2)slag melts

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 70-79页

作者： Yong hou Shuo Zhang Jie Dang Jia Guo hanghang Zhou Xuewei lü College of Materials Science and Engineering Chongqing UniversityChongqing 400044China Chongqing key laboratory of Vanadium-Titanium Metallurgy and New Materials Chongqing UniversityChongqing 400044China

Currently,the Al_(2)O_(3)content in the high-alumina slag systems within blast furnaces is generally limited to 16wt%–18.5wt%,making it challenging to overcome this *** most studies that concentrated on managing the MgO/Al_(2)O_(3)ratio or basicity,this paper explored the effect of equimolar substitution of MgO for CaO on the viscosity and structure of a high-alumina CaO-MgO-Al_(2)O_(3)-SiO_(2)slag system,providing theoretical guidance and data to facilitate the application of high-alumina *** results revealed that the viscosity first decreased and then increased with higher MgO substitution,reaching a minimum at 15mol%MgO *** transform infrared spectroscopy(FTIR)results found that the depths of the troughs representing[SiO_(4)]tetrahedra,[AlO_(4)]tetrahedra,and Si-O-Al bending became progressively deeper with increased MgO *** of the Raman spectra showed that the average number of bridging oxygens per Si atom and the X_(Q^(3))/X_(Q^(2))(X_(Q^(i))is the molar fraction of Q^(i) unit,and i is the number of bridging oxygens in a[SiO_(4)]tetrahedral unit)ratio increased from 2.30 and 1.02 to 2.52 and 2.14,respectively,indicating a progressive polymerization of the silicate structure.X-ray photoelectron spectroscopy(XPS)results highlighted that non-bridging oxygen content decreased from 77.97mol% to 63.41mol% with increasing MgO concentration,whereas bridging oxygen and free oxygen contents *** analysis demonstrated a gradual increase in the polymerization degree of the tetrahedral structure with the increase in MgO ***,bond strength is another important factor affecting the slag *** occurrence of a viscosity minimum can be attributed to the complex evolution of bond strengths of non-bridging oxygens generated during depolymerization of the[SiO_(4)]and[AlO_(4)]tetrahedral structures by CaO and MgO.

关键词： aluminosilicate viscosity structure spectroscopy

Activation characteristics of candidate structural materials for a near-term Indian fusion reactor and the impact of their impurities on design considerations

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Plasma Science and Technology 2018年第6期20卷 186-193页

作者： h l SWAMI C DANANI A k ShAW Institute for Plasma Research Gandhinagar Gujarat 382428 India homi Bhabha National Institute (hBNI) Anushaktinagar Mumbai 400094 India

Activation analyses play a vital role in nuclear reactor *** analyses,along with nuclear analyses,provide important information for nuclear safety and maintenance *** analyses also help in the selection of materials for a nuclear reactor,by providing the radioactivity and dose rate levels after *** information is important to help define maintenance activity for different parts of the reactor,and to plan decommissioning and radioactive waste disposal *** study of activation analyses of candidate structural materials for near-term fusion reactors or ITER is equally essential,due to the presence of a highenergy neutron environment which makes decisive demands on material *** study comprises two parts; in the first part the activation characteristics,in a fusion radiation environment,of several elements which are widely present in structural materials,are *** reveals that the presence of a few specific elements in a material can diminish its feasibility for use in the nuclear *** second part of the study concentrates on activation analyses of candidate structural materials for near-term fusion reactors and their comparison in fusion radiation *** structural materials selected for this study,***-specific Reduced Activation Ferritic-Martensitic steel（IN-RAFMS）,P91-grade steel,stainless steel 316 lN ITER-grade（SS-316 lN-IG）,stainless steel 316 l and stainless steel 304,are candidates for use in ITER either in vessel components or test blanket *** is also included in this study because of its use for ITER plasma-facing *** study is carried out using the reference parameters of the ITER fusion *** activation characteristics of the materials are assessed considering the irradiation at an ITER equatorial *** presence of elements like Nb,Mo,Co and Ta in a structural material enhance the activity level as well as the dose level,which has an

关键词： activation EASY nuclear safety fusion reactor structural materials

Direct joining of oxygen-free copper and carbon-fiber-reinforced plastic by friction lap joining

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Journal of Materials Science & Technology 2018年第1期34卷 192-197页

作者： l.h. Wu k. Nagatsuka k. Nakata Joining and Welding Research Institute Osaka University 11-1 Mihogaoka Ibaraki Osaka 567-0047 Japan

Oxygen-flee copper （Cu） was successfully joined to carbon-fiber-reinforced thermoplastic （CFRTP, polyamide 6 with 20wt% carbon fiber addition） by friction lap joining （FlJ） at joining speeds of 200-1600 mm/min with a constant rotation rate of 1500 rpm and a nominal plunge depth of 0.9 ram. It is the first time to report the joining of CFRTP to Cu by FlJ. As the joining speed increased, the tensile shear force （TSF） of joints increased first, and decreased thereafter. The maximum TSF could reach 2.3 kN （ 15 mm in width）. hydrogen bonding formed between the amide group of CFRTP and the thin Cu20 layer on the Cu surface, which mainly contributed to the joint bonding. The influence factors of the TSF of the joints at different joining speeds were discussed. The TSF was mainly affected by the joining area, the degradation of the plastic matrix and the number and the size of bubbles. As the joining speed increased, the influence factors varied as follows： the joining area increased first and then decreased; the degra- dation of the plastic matrix and the number and the size of bubbles decreased. The maximum TSF was the comprehensive result of the relatively large joining area, small degradation of the plastic matrix and small number and sizes of bubbles.

关键词： Friction lap joining Metal Plastic Carbon-fiber reinforced thermoplastic Dissimilar materials joining