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BAcE1 elevation in transgenic mouse model of Alzheimer’s disease is associated with synaptic/axonal pathology and amyloidogenesis

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BACE1 elevation in transgenic mouse model of Alzheimer’s di...

Longitudinal diffusion tensor magnetic resonance imaging analysis at the cohort level reveals disturbed cortical and callosal microstructure with spared corticospinal tract in the TDP-43^(G298S) ALS mouse model

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： philip c.wong P.R.PATRYLO Department of Pathology and Neuroscience The Johns Hopkins University School of MedicineBaltimoreMaryland 21205 Department of Anatomy Southern Illinois University School of MedicineCarbondaleIllinois 62901

＜正＞How amyloid plaques develop in the brain represents the central yet unsettled question in Alzheimer’s disease （AD） *** hypothesis postulate thatβ-amyloid peptide（Ap） deposits are either the cause or the consequence of vascular,glial and neuronal *** proteins includingβ-amyloid precursor protein （APP）,and its cleavage enzymes,β-secretase（BAcE1） andβ-secretase,appear to be expressed largely in neurons, supporting a notion that Aβdeposits originate from neuronal *** depositions may exist either as neuritic or diffuse forms,with the former being associated with dystrophic *** phenomenon appears as if dystrophic neurites and Aβdeposits do not necessarily precede one to *** and axonal terminals have been considered the origin of extracellular Aβ***,anatomic evidence for early synaptic/axonal alterations preceding or coevolving with plaque onset and evolution is yet to be *** study determined the localization of elevated BAcE1 expression relative to Aβaccumulation and synaptic/neuritic alterations in transgenic（Tg） mice harboring familial AD（FAD） mutations（5XFAD,2XFAD,3xTg-AD mice）.BAcE1 immunoreactivity（ir） coexisted with compact plaques in the cortex and hippocampus of all transgenics,occurring in dystrophic axonal neurites of various neuronal origins（GABAergic,glutamatergic,cholinergic or catecholaminergic）.compact plaques within the cortical grey matter appeared to mainly derive from BAcE/Aβlabeled presynaptic terminals surrounding pyramidal neurons with cytoplasmic Aβ-ir,and some of these terminals undergone sprouting to become overt dystrophic *** plaques appeared to evolve into cored plaques as extracellular Aβaccumulated within/around the growing mass of sprouting dystrophic *** old 3xTg-AD mice,the superficial cortical layers largely expressed diffuse plaques. Development of these diffuse plaques with age was associated with increased BAcE

关键词： aging dementia secretase amyloid plaques dystrophic neurite axonopathy

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Translational Neurodegeneration 2019年第1期8卷 333-345页

作者： Hans-Peter Müller David Brenner Francesco Roselli Diana Wiesner Alireza Abaei Martin Gorges Karin M.Danzer Albert c.Ludolph William Tsao philip c.wong Volker Rasche Jochen H.Weishaupt Jan Kassubek Department of Neurology University of UlmOberer Eselsberg 45RKUD-89081 UlmGermany German center for Neurodegenerative Diseases(DZNE) UlmGermany core Facility Small Animal MRI University of UlmUlmGermany Department of Pathology The Johns Hopkins University School of MedicineBaltimoreUSA

Background:In vivo diffusion tensor imaging(DTI)of the mouse brain was used to identify TDP-43 associated alterations in a mouse model for amyotrophic lateral sclerosis(ALS).Methods:Ten mice with TDP-43^(G298S) overexpression under control of the Thy1.2 promoter and 10 wild type(wt)underwent longitudinal DTI scans at 11.7 T,including one baseline and one follow-up scan with an interval of about *** brain-based spatial statistics(WBSS)of DTI-based parameter maps was used to identify longitudinal alterations of TDP-43^(G298S) mice compared to wt at the cohort *** were supplemented by tractwise fractional anisotropy statistics(TFAS)and histological evaluation of motor cortex for signs of neuronal ***:Alterations at the cohort level in TDP-43^(G298S) mice were observed cross-sectionally and longitudinally in motor areas M1/M2 and in transcallosal fibers but not in the corticospinal *** loss in layer V of motor cortex was detected in TDP-43^(G298S) at the later(but not at the earlier)timepoint compared to ***:DTI mapping of TDP-43^(G298S) mice demonstrated progression in motor areas M1/*** and TFAS are useful techniques to localize TDP-43^(G298S) associated alterations over time in this ALS mouse model,as a biological marker.

关键词： Diffusion tensor imaging Amyotrophic lateral sclerosis Mutant TDP-43 Fiber tracking Mouse brain

Dynamic Event-Triggered consensus control for Input constrained Multi-Agent Systems With a Designable Minimum Inter-Event Time

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IEEE/cAA Journal of Automatica Sinica 2024年第3期11卷 649-660页

作者： Meilin Li Yue Long Tieshan Li Hongjing Liang c.L.philip chen the School of Automation Engineering University of Electronic Science and Technology of ChinaChengdu 611731China IEEE the Yangtze Delta Region Institute University of Electronic Science and Technology of ChinaHuzhou 313000 the Laboratory of Electromagnetic Space cognition and Intelligent control Beijing 100089China the School of computer Science and Engineering South China University of TechnologyGuangzhou 510006

This paper investigates the consensus control of multi-agent systems(MASs) with constrained input using the dynamic event-triggered mechanism(ETM).consider the MASs with small-scale networks where a centralized dynamic ETM with global information of the MASs is first ***,a distributed dynamic ETM which only uses local information is developed for the MASs with large-scale *** is shown that the semi-global consensus of the MASs can be achieved by the designed bounded control protocol where the Zeno phenomenon is eliminated by a designable minimum inter-event *** addition,it is easier to find a trade-off between the convergence rate and the minimum inter-event time by an adjustable ***,the results are extended to regional consensus of the MASs with the bounded control *** simulations show the effectiveness of the proposed approach.

关键词： constrained input designable minimum inter-event time directed communication topology dynamic event-triggered mechanism MASs consensus control

Adaptive neural network control of a 2-DOF helicopter system considering input constraints and global prescribed performance

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Science china(Information Sciences) 2024年第7期67卷 224-239页

作者： Zhijia ZHAO Jiale WU Zhijie LIU We HE c.L.philip cHEN School of Mechanical and Electrical Engineering Guangzhou University School of Intelligence Science and Technology and Key Laboratory of Intelligent Bionic Unmanned Systems of Ministry of Education University of Science and Technology Beijing School of computer Science and Engineering South China University of Technology Pazhou Lab

In this study, an adaptive neural network(NN) control is proposed for nonlinear two-degree-offreedom(2-DOF) helicopter systems considering the input constraints and global prescribed ***, radial basis function NN(RBFNN) is employed to estimate the unknown dynamics of the helicopter system. Second, a smooth nonaffine function is exploited to approximate and address nonlinear constraint functions. Subsequently, a new prescribed function is proposed, and an original constrained error is transformed into an equivalent unconstrained error using the error transformation and barrier function transformation methods. The analysis of the established Lyapunov function proves that the controlled system is globally uniformly bounded. Finally, the simulation and experimental results on a constructed Quanser's test platform verify the rationality and feasibility of the proposed control.

关键词： adaptive NN control 2-DOF helicopter global prescribed performance input constraints

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Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 146-153页

作者： philip c.Muller Matthias Pfister Dilmurodjon Eshmuminov Kuno Lehmann Department of Surgery and Transplantation University Hospital ZurichRämistrasse 100Zurich CH-8091Switzerland

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in *** comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is *** goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of *** sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March ***:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed *** liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free *** highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are *** factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic *** on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to *** benefits of LT were lost in patients beyond the Milan ***:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to *** evidence suggests even stricter selection criteria with regard to tumor biology.

关键词： Liver transplantation Neuroendocrine liver metastases Liver resection Selection criteria Tumor biology

Mass spectrometry-based proteomics technology in pancreatic cancer research

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胰腺病学杂志(英文) 2024年第2期7卷 145-163页

作者： Sun Xue Wang Siyuan wong catherine c.L. First School of clinical Medicine Peking University Health Science Center Peking University Beijing China School of Pharmacy University of Wisconsin-Madison Madison Wisconsin United States State Key Laboratory of complex Severe and Rare Diseases Clinical Research Institute Peking Union Medical College Hospital Chinese Academy of Medical Science &amp Peking Union Medical college Beijing China Tsinghua-Peking University Joint center for Life Sciences Tsinghua University Beijing China

Pancreatic ductal adenocarcinoma (PDAc) has become a significant health concern with increasing incidence and mortality rates over the past few decades. Researchers have turned their attention to cutting-edge mass spectrometry (MS) technology due to its high-throughput and accurate detection capacity, which plays a vital role in understanding the mechanisms and discovering biomarkers for pancreatic diseases. In this review, we comprehensively investigate various methodologies of quantitative and qualitative proteomics MS technologies, alongside bioinformatical platforms employed in pancreatic cancer research. The integration of these optimized approaches provides novel insights into the molecular mechanisms underlying tumorigenesis and disease progression, ultimately facilitating the discovery of potential diagnostic, prognostic biomarkers, and therapeutic targets. The robust MS-based strategy shows promise in paving the way for early diagnosis and personalized medicine for pancreatic cancer patients.

关键词： Biomarkers Mass spectrometry Pancreatic cancer Pancreatic ductal adenocarcinoma Proteomics

Free-electron crystals for enhanced X-ray radiation

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Light(Science & Applications) 2024年第7期13卷 1299-1309页

作者： Lee Wei Wesley wong Xihang Shi Aviv Karnieli Jeremy Lim Suraj Kumar Sergio carbajo Ido Kaminer Liang Jie wong School of Electrical and Electronic Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore. Solid State Institute and Faculty of Electrical and computer Engineering Technion–Israel Institute of TechnologyHaifa 3200003Israel. School of Electrical Engineering Fleischman Faculty of EngineeringTel Aviv UniversityTel Aviv 69978Israel Department of Applied Physics Stanford UniversityStanfordCA 94305USA. Science Mathematics and TechnologySingapore University of Technology and Design8 Somapah RoadSingapore 487372Singapore. Electrical and computer Engineering Department UCLA420 WestwoodLos AngelesCA 90095USA. Physics and Astronomy Department UCLA475 Portola PlazaLos AngelesCA 90095USA. SLAc National Accelerator Laboratory Stanford University2575 Sand Hill RoadMenlo ParkCA 94025USA

Bremsstrahlung—the spontaneous emission of broadband radiation from free electrons that are deflected by atomic nuclei—contributes to the majority of X-rays emitted from X-ray tubes and used in applications ranging from medical imaging to semiconductor chip ***,we show that the bremsstrahlung intensity can be enhanced significantly—by more than three orders of magnitude—through shaping the electron wavefunction to periodically overlap with atoms in crystalline ***,we show how to shape the bremsstrahlung X-ray emission pattern into arbitrary angular emission profiles for purposes such as unidirectionality and ***,we find that these enhancements and shaped emission profiles cannot be attributed solely to the spatial overlap between the electron probability distribution and the atomic centers,as predicted by the paraxial and nonrecoil theory for free electron light *** work highlights an unprecedented regime of free electron light emission where electron waveshaping provides multi-dimensional control over practical radiation processes like *** results pave the way towards greater versatility in table-top X-ray sources and improved fundamental understanding of quantum electron-light interactions.

关键词： overlap attributed arbitrary

Distinct vibrational signatures and complex phase behavior in metallic oxygen

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Matter and Radiation at Extremes 2024年第2期9卷 4-11页

作者： philip Dalladay-Simpson Bartomeu Monserrat Li Zhang Federico Gorelli center for High Pressure Science Technology Advanced Research 1690 Cailun RoadShanghai 201203China Department of Materials Science and Metallurgy University of Cambridge27 Charles Babbage RoadCambridge CB3 OFSUnited Kingdom cavendish Laboratory University of CambridgeJ.J.Thomson AvenueCambridge CB3 OHEUnited Kingdom Istituto Nazionale di Ottica Consiglio Nazionale delle Ricerche(CNR-INO)50125 FlorenceItaly Shanghai Advanced Research in Physical Sciences(SHARPS) ShanghaiChina

Evidence for metallization in dense oxygen has been reported for over 30 years[Desgreniers et al.,***.94,1117(1990)]at a now routinely accessible 95 GPa[Shimizu et al.,Nature 393,767(1998)].However,despite the longevity of this result and the technological advances since,the nature of the metallic phase remains poorly constrained[Akahama et al.,***.74,4690(1995);Goncharov et al.,***.B 68,224108(2003);Ma,***.B 76,064101(2007);and Weck et al.,***.102,255503(2009)].In this work,through Raman spectroscopy,we report the distinct vibrational characteristics of metallicζ-O_(2) from 85 to 225 *** comparison with numerical simulations,weﬁnd reasonable agreement with the candidate structure up to about 150 *** higher pressures,the c2/mstructure is found to be unstable and incompatible with experimental *** candidate structures,and ci,with c2/m c2/conly two molecules in the primitive unit cell,are found to be stable and more compatible with measurements above 175 GPa,indicative of the dissociation of(O_(2))4 ***,we report and discuss a strong hysteresis and metastability with the precursory phaseϵ-O_(2).Theseﬁndings will reinvigorate experimental and theoretical work into the dense oxygen system,which will have importance for oxygen-bearing chemistry,prevalent in the deep Earth,as well as fundamental physics.

关键词： metallic phase vibrational

MicroRNAs as potential biomarkers for diagnosis of post-traumatic stress disorder

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Neural Regeneration Research 2025年第7期20卷 1957-1970页

作者： Bridget Martinez philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life ***,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress *** addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate *** suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress *** performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December *** included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum *** of these studies had also used whole *** studies were excluded as they did not involve microRNA *** of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult *** measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString *** six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to *** miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/

关键词： biomarker diagnosis microRNA peripheral blood mononuclear cells plasma extracellular vesicles/exosomes post-traumatic stress disorder serum exosomes whole blood whole plasma