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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

Axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders

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Neural Regeneration Research 2021年第10期16卷 1901-1910页

作者： Katherine l.Marshall mohamed H.Farah Department of Neurology at Johns Hopkins School of Medicine BaltimoreMDUSA

Nervous system disorders are prevalent health issues that will only continue to increase in frequency as the population ***-back axonopathy is a hallmark of many neurologic diseases and leads to axonal disconnection from their targets,which in turn leads to functional *** the course of many of neurologic diseases,axons can regenerate or sprout in an attempt to reconnect with the target and restore synapse *** amyotrophic lateral sclerosis(AlS),distal motor axons retract from neuromuscular junctions early in the disease-course before significant motor neuron *** is evidence of compensatory motor axon sprouting and reinnervation of neuromuscular junctions in AlS that is usually quickly overtaken by the disease *** drugs that enhance compensatory sprouting and encourage reinnervation may slow symptom progression and retain muscle function for a longer period of time in AlS and in other diseases that exhibit dying-back *** remain many outstanding questions as to the impact of distinct disease-causing mutations on axonal outgrowth and regeneration,especially in regards to motor neurons derived from patient induced pluripotent stem *** microfluidic chambers are powerful tools for studying the distal axons of human induced pluripotent stem cells-derived motor neurons,and have recently been used to demonstrate striking regeneration defects in human motor neurons harboring AlS disease-causing *** the human neuromuscular circuit with human induced pluripotent stem cells-derived motor neurons will be critical for developing drugs that enhance axonal regeneration,sprouting,and reinnervation of neuromuscular *** this review we will discuss compensatory axonal sprouting as a potential therapeutic target for AlS,and the use of compartmentalized microfluidic devices to find drugs that enhance regeneration and axonal sprouting of motor axons.

关键词： amyotrophic lateral sclerosis axonal regeneration dying-back axonopathy in vitro neuromuscular junction iPSC-derived motor neurons microfluidic device motor axon sprouting

Excimer laser 6^(th)generation:state of the art and refractive surgical outcomes

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Eye and Vision 2015年第1期2卷 44-52页

作者： mohamed El Bahrawy Jorge l Alió Vissum Corporación Alicante AlicanteSpain Division of Ophthalmology Universidad Miguel HernándezAlicanteSpain Clinical research fellow in Vissum Corporación Alicante Universidad Miguel HernándezAlicanteSpain Avda de Denia s/n Edificio Vissum03016 AlicanteSpain

After nearly three decades of innovation in excimer laser,today we are presented with a state of the art generation targeting minimally invasive refractive surgery with high speed laser,faster trackers,pupil monitoring systems and better customization *** systems are capable of delivering better treatments with less induced postoperative high order *** results reported by many authors had confirmed the superiority in efficiency and safety profiles of this generation compared to previous ***,current technology is facing major challenges in the correction of high hyperopic errors and in presbyopic treatments,with upgrades in ablation centration and thermal control needed,which will ensure better biomechanical results,as a step closer to perfection in refractive surgery.

关键词： Refractive surgery Excimer laser 6^(th)Generation

Real-time stereo matching on CUDA using Fourier descriptors and dynamic programming

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Computational Visual Media 2019年第1期5卷 59-71页

作者： mohamed Hallek Fethi Smach mohamed Atri Faculty of Sciences of Monastir Technologies et services de l'information

Computation of stereoscopic depth and disparity map extraction are dynamic research topics.A large variety of algorithms has been developed,among which we cite feature matching, moment extraction, and image representation using descriptors to determine a disparity map. This paper proposes a new method for stereo matching based on Fourier descriptors. The robustness of these descriptors under photometric and geometric transformations provides a better representation of a template or a local region in the image. In our work, we specifically use generalized Fourier descriptors to compute a robust cost ***, a box filter is applied for cost aggregation to enforce a smoothness constraint between neighboring pixels. Optimization and disparity calculation are done using dynamic programming, with a cost based on similarity between generalized Fourier descriptors using Euclidean distance. This local cost function is used to optimize correspondences. Our stereo matching algorithm is evaluated using the Middlebury stereo benchmark; our approach has been implemented on parallel high-performance graphics hardware using CUDA to accelerate our algorithm, giving a real-time implementation.

关键词： generalized Fourier descriptors stereo matching dynamic programming CUDA

Cardiac drug therapy--considerations in the elderly

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Journal of Geriatric Cardiology 2016年第12期13卷 992-997页

作者： mohamed Ayan Naga Venkata Pothineni Aisha Siraj Jawahar l Mehta Division of Cardiovascular Medicine University of Arkansas for Medical Sciences Little Rock AR USA

Elderly individuals constitute a majority of patients encountered in current cardiovascular clinical practice. Management of these patients is a clinical challenge owing to a multitude of factors. Although medications such as statins have been shown to reduce cardiovascular mortality in the general population, evidence supporting the use of these drugs in patients greater than 75 years of age is sparse. Furthermore, aging associated changes in organ function and associated comorbidities influence the pharmacokinetics of multiple medications and can potentiate drug toxicity. In this article, we review the evidence behind the use of common cardiovasctdar medications in elderly patients and discuss pertinent clinical challenges.

关键词： Cardiac Drugs Elderly

Optimization of fused deposition modeling process parameters:a review of current research and future prospects

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Advances in Manufacturing 2015年第1期3卷 42-53页

作者： Omar A.mohamed Syed H.Masood Jahar l.Bhowmik Department of Mechanical and Product Design Engineering Faculty of ScienceEngineering and TechnologySwinburne University of TechnologyHawthornMelbourneAustralia Department of Psychological Sciences and Statistics Faculty of HealthArts and DesignSwinburne University of TechnologyHawthornMelbourneAustralia

Fused deposition modeling （FDM） is one of the most popuIar additive manufacturing technologies for various engineering applications. FDM process has been introduced commercially in early 1990s by Stratasys Inc., USA. The quality of FDM processed parts mainly depends on careful selection of process variables. Thus, identifica- tion of the FDM process parameters that significantly affect the quality of FDM processed parts is important. In recent years, researchers have explored a number of ways to improve the mechanical properties and part quality using various experimental design techniques and concepts. This article aims to review the research carried out so far in determining and optimizing the process parameters of the FDM process. Several statistical designs of experiments and optimization techniques used for the determination of optimum process parameters have been examined. The trends for future FDM research in this area are described.

关键词： Fused deposition modeling (FDM) -Experimental design. Additive manufacturing. Processparameters. Mechanical properties.Part quality

Innovative surfactant of Gemini-type for dissolution mitigation of steel in pickling HCl medium

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Chinese Journal of Chemical Engineering 2021年第6期34卷 125-133页

作者： Medhat Kamel mohamed Hegazy Salah Rashwan mohamed El Kotb Department of Chemistry Faculty of ScienceSuez Canal UniversityIsmailia 41522Egypt Egyptian Petroleum Research Institute(EPRI) Nasr CityCairo 11727Egypt

A new surfactant of Gemini-type,N,N'-((phthylbis(oxy))bis(ethane-2,1-diyl))bis(N,N-dimethyldodecan-1-aminium bromide)is prepped&*** dissolution suppression impact of the new compound on steel is performed in 1 mol·l^(-1)HCl environment by means of chemical and electrochemical *** prepared surfactant is an agreeable dissolution inhibitor for *** mitigation efficacy rises with the quantity of the *** surfactant belongs to inhibitors of *** adsorption of the synthesized compound followed the langmuir's *** negative magnitudes of bothΔG_(ads)^(θ) andΔH^(adsθ)indicate that the adsorption process proceeds from its own accord and *** mechanism of adsorption is elucidated by scanning *** is established that the transfer resistance(R_(ct))value rose,where the value of the phase element(CPE)reduced with the amount of synthesized *** to the experimental data arrived by surface tension measurements,the prepared compound is a powerful active agent at the air/water boundary.

关键词： Innovative Gemini surfactant Synthesis Dissolution mitigation Steel Pickling HCl media

Modified malleable prosthesis with a fixed mesh:case series for the Ghattas technique

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Asian Journal of Andrology 2022年第2期24卷 167-170页

作者： Osama Ghattas mohamed Fahmy Doheim Hossam Kotb Arthur l Burnett Dar-elzokora Center of Andrology Alexandria 21500Egypt Alexandria Faculty of Medicine Alexandria UniversityAlexandria 21131Egypt Department of Urology Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Penile prosthetic implantation represents a cornerstone for patients with organic erectile dysfunction(ED)that is refractory,unsatisfactory,or contra-indicated for other approved medical or mechanical *** this study,we introduce the“Ghattas technique,”wherein we constructed a polypropylene mesh sheath that surrounds and is fixed to a 13-mm malleable prosthesis cylinder,which can increase the cylinder diameter for cases that need a larger *** patients underwent preoperative evaluation and completed the five-item International Index of Erectile Function questionnaire(IIEF-5).Postoperative outcomes were evaluated by IIEF-5 and Erectile Dysfunction Inventory of Treatment Satisfaction(EDITS)questionnaires at final *** mean age of the 23 included patients was 57.9(standard deviation[s.d.]:11.4)years and the mean duration of ED was 8.5(s.d.:7.9)*** improvement was determined by comparing mean preoperative and postoperative IIEF-5 scores(8.3[s.d.:3.9]vs 24.6[s.d.:0.6],Plarger than 13 *** studies are needed to confirm these results.

关键词： erectile dysfunction mesh penile prosthesis surgical technique

Programmed death-1/programmed death-l1 signaling pathway and its blockade in hepatitis C virus immunotherapy

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World Journal of Hepatology 2015年第23期7卷 2449-2458页

作者： mohamed l Salem Ahmed El-Badawy Center of Excellence in Cancer Research Tanta University Immunology and Biotechnology Division Zoology Department Faculty of Science Center of Excellence for Stem Cells and Regenerative Medicine Zewail City of Science and Technology

Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes(CTls) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-l1 function in a T cell co-inhibitory pathway, which either blocks the function of CTls or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-l1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-l1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy.

关键词： Hepatitis C virus Programmed death-1 Hepatitis C v