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sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica s.Brady michael T.Craig Department of Clinical and Biomedical sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA school of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday activities.It is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 trillion.Around 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao michael s.Wolfe Computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface receptors.Mutations inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as well.However,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-secretase.In this review,we focus on recent studies of structural dynamic mechanisms ofγ-secretase.Different mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics simulations.While an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental findings.The approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-secretase.In addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is discussed.Finally,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations of theγ-secretase-substrate complexes.Comprehen

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

Application of a simplified ADM1 for full-scale anaerobic co-digestion of cattle slurry and grass silage:assessment of input variability

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Frontiers of Environmental science & Engineering 2024年第4期18卷 125-139页

作者： sofia Tisocco sören Weinrich Gary Lyons michael Wills Xinmin Zhan Paul Crosson Civil Engineering College of Science and EngineeringUniversity of GalwayGalwayH91 TK33Ireland Teagasc Animal and Bioscience Research Department Animal and Grassland Research and Innovation CentreDunsanyC15 PW93Ireland Biochemical Conversion Department Deutsches Biomasseforschungszentrum gemeinnützige GmbHLeipzig 04347Germany Faculty of Energy·Building services·Environmental Engineering Münster University of Applied SciencesSteinfurt 48565Germany Agri-Food and Biosciences Institute HillsboroughBT266DRUK Ryan Institute University of GalwayGalwayH91 TK33Ireland MaREI Research Centre for Energy Climate and MarineRyan InstituteUniversity of GalwayGalwayH91 TK33Ireland

Mathematical modeling of anaerobic digestion is a powerful tool to predict gas yields and optimize the process.The Anaerobic Digestion Model No.1(ADM1)is a widely implemented model for this purpose.However,modeling full-scale biogas plants is challenging due to the extensive substrate and parameter characterization required.This study describes the modification of the ADM1 through a simplification of individual process phases,characteristic components and required parameters.Consequently,the ability of the simplified model to simulate the co-digestion of grass silage and cattle slurry was evaluated using data from a full-scale biogas plant.The impacts of substrate composition(crude carbohydrate,protein and lipid concentration)and variability of carbohydrate degradability on simulation results were assessed to identify the most influential parameters.Results indicated that the simplified version was able to depict biogas and biomethane production with average model efficiencies,according to the Nash-sutcliffe efficiency(NsE)coefficient,of 0.70 and 0.67,respectively,and was comparable to the original ADM1(average model efficiencies of 0.71 and 0.63,respectively).The variability of crude carbohydrate,protein and lipid concentration did not significantly impact biogas and biomethane output for the data sets explored.In contrast,carbohydrate degradability seemed to explain much more of the variability in the biogas and methane production.Thus,the application of simplified models provides a reliable basis for the process simulation and optimization of full-scale agricultural biogas plants.

关键词： ADM1 Agricultural feedstocks Biogas technology Input variability Parameter estimation

A review of control strategies used for morphing aircraft applications

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Chinese Journal of Aeronautics 2024年第4期37卷 436-463页

作者： Muhammed s.PARANCHEERIVILAKKATHIL Jafar s.PILAKKADAN Rafic M.AJAJ Mohammadreza AMOOZGAR Davood AsADI Yahya ZWEIRI michael I.FRIsWELL Department of Aerospace Engineering Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of Aerospace Engineering Advanced Research and Innovation Center(ARIC)Khalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates Department of Mechanical Materials&Manufacturing EngineeringUniversity of NottinghamNottingham NG72RDUK Department of Aerospace Engineering Adana Alparslan Turkes Science and Technology UniversityTurkey College of Engineering Swansea UniversitySwansea SA18ENUK

This paper reviews the various control algorithms and strategies used for fixed-wing morphing aircraft applications. It is evident from the literature that the development of control algorithms for morphing aircraft technologies focused on three main areas. The first area is related to precise control of the shape of morphing concepts for various flight conditions. The second area is mainly related to the flight dynamics, stability, and control aspects of morphing aircraft. The third area deals mainly with aeroelastic control using morphing concepts either for load alleviation purposes and/or to control the instability boundaries. The design of controllers for morphing aircraft/wings is very challenging due to the large changes that can occur in the structural, aerodynamic, and inertial characteristics. In addition, the type of actuation system and actuation rate/speed can have a significant effect on the design of such controllers. The aerospace community is in strong need of such a critical review especially as morphing aircraft technologies move from fundamental research at a low Technology Readiness Level(TRL) to real-life applications. This critical review aims to identify research gaps and propose future directions. In this paper, research activities/papers are categorized according to the control strategy used. This ranges from simple Proportional Integral Derivative(PID) controllers at one end to complex robust adaptive controllers and deep learning algorithms at the other end. This includes analytical, computational, and experimental studies. In addition, the various dynamic models used and their fidelities are highlighted and discussed.

关键词： Control strategies Morphing aircraft shape morphing Flight dynamics Aeroelasticity

Transcranial photobiomodulation for the brain: a wide range of clinical applications

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Neural Regeneration Research 2024年第3期19卷 483-484页

作者： michael R.Hamblin Laser Research Centre Faculty of Health ScienceUniversity of Johannesburg-Doornfontein CampusDoornfonteinSouth Africa

Photobiomodulation therapy(PBMT)is a rapidly growing approach to the healing,stimulation,protection,and regeneration of many human organs and tissue types.PBMT started in the 1960s as low-level laser therapy for wound healing,but since then the introduction of light-emitting diodes(LEDs)has dramatically increased the number of applications and reports of positive results.PBMT generally uses red(620-700 nm)and/or near-infrared(780-1270 nm)wavelengths of light at an intensity that causes no tissue heating,and its activity is based on well-established biological and cellular mechanisms(de Freitas and Hamblin,2016).While laser therapists continue to use various types of laser in their office practice,LEDs are ideally suited for home use devices because they are completely safe and without any known significant adverse effects.Among the various body parts on which PBMT has been shown to exert beneficial effects,the brain stands out as perhaps the most promising overall.PBMT has been shown to reduce neuroinflammation,while increasing mitochondrial function,oxygen consumption,and blood flow within the brain(Hamblin,2016).Moreover,PBMT can stimulate the processes of synaptogenesis,neurogenesis,and neuroplasticity thus helping the brain to heal itself.

关键词： healing stimulation wound

Comparison of trigeminal lateralization with differing stimulants

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World Journal of Otorhinolaryngology-Head and Neck surgery 2024年第1期10卷 66-69页

作者： Tiffany Chen Nicolas s.Poupore michael C.shih Thomas s.Edwards shaun A.Nguyen Zachary M.soler Rodney J.schlosser Department of Otolaryngology‐Head and Neck surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory perception.It is unclear whether trigeminal sensitivity is similar across different transient receptor potential(TRP)receptors or if dysfunction of different receptors results in differing patient symptoms.Therefore,a prospective cohort study was conducted,consisting of trigeminal lateralization testing with three different stimulants(eucalyptol,isothiocyanate,acetic acid),olfaction testing with sniffin'sticks,and measurement of various patient‐reported outcome measures(PROMs).A total of 50 participants were enrolled across the olfactory spectrum.Mean TDI score was 27.1±8.3(range 7.0–39.5)with 38%normosmic and 62%dysosmic.Mean trigeminal lateralization scores out of 20 in the overall cohort were 16.18(2.78)for eucalyptol,14.94(3.49)for mustard oil,and 15.28(3.68)for vinegar.Eucalyptol showed a significant correlation with threshold scores of sniffin'sticks.A significant correlation was found between acetic acid and various PROMs.None of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to age.The lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other receptors.Additional investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

关键词： chemosensory olfaction trigeminal TRP receptor

A 63-Year-Old Male with D-Transposition of the Great Arteries Who Had an Early Form of the Arterial switch Operation

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Congenital Heart Disease 2024年第1期19卷 65-68页

作者： michael A.Rebolledo Jane s.Yao Jason N.Johnson Umar s.Boston Benjamin R.Waller III Division of Pediatric Cardiology Department of PediatricsThe University of Tennessee Health Science CenterThe Heart InstituteLe Bonheur Children’s HospitalMemphisUSA College of Medicine The University of Tennessee Health ScienceMemphisUSA Division of Pediatric Cardiothoracic surgery Department of SurgeryThe University of Tennessee Health Science CenterHeart InstituteLe Bonheur Children’s HospitalMemphisUSA

We describe a 63-year-old male who appears to have undergone an early form of the arterial switch operation for D-transposition of the great arteries performed in the mid-1960s.We review the clinical and imaging data that support our conclusion.He had a diagnostic cardiac catheterization which demonstrated severe pulmonary hypertension responsive to epoprostenol and oxygen.Our case may represent one example of the experimental surgical work done prior to Dr.Adibe Jatene’s description of theﬁrst successful arterial switch performed in 1975.

关键词： Adult congenital heart disease arterial switch operation great vessel anomaly imaging(all modalities)

Diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

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signal Transduction and Targeted Therapy 2024年第4期9卷 1245-1246页

作者： Christian Herder michael Roden Nicolas Venteclef Institute for Clinical Diabetology German Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf40225DüsseldorfGermany German Center for Diabetes Research(DZD) Partner Düsseldorf85764München-NeuherbergGermany Department of Endocrinology and Diabetology Medical Faculty and University Hospital DüsseldorfHeinrich Heine University Düsseldorf40225DüsseldorfGermany Institut Necker-Enfants Malades(INEM) UniversitéParis CitéINSERM UMR-S1151CNRS UMR-S8253ParisFrance

In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

关键词： impaired lung respiratory

Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： michael Hiltensperger Jürgen Ruland Kilian schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer Consortium(DKTK) HeidelbergGermany German Center for Infection Research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et al.use a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： al. cancer potential