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The plasminogen activating system in the pathogenesis of Alzheimer’s disease

Neural Regeneration Research 2021年第10期16卷 1973-1977页

作者： manuel Yepes Department of Neurology Emory University School of MedicineAtlantaGAUSA Department of Neurology Veterans Affairs Medical CenterAtlantaGAUSA Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research CenterAtlantaGAUSA

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor ***’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated ***,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular *** observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain *** plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of ***,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular *** contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβ*** we discuss the role of the PA system in the pathogenesis of AD and

关键词： Alzheimer’s disease amyloid precursor protein amyloidβ neuroserpin plasmin plasminogen activating system plasminogen activator inhibitor-1 synapse tissue-type plasminogen activator urokinase-type plasminogen activator

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Positive curvature, symmetry, and topology

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Frontiers of Mathematics in China 2016年第5期11卷 1099-1122页

作者： manuel AMANN Fakultat fur Mathematik Institut fiir Algebra und Geometrie Karlsruher Institut fiir Technologie Englerstraβe 2 76131 Karlsruhe Germany

We depict recent developments in the field of positive sectional curvature, mainly, but not exclusively, under the assumption of isometric torus actions. After an elaborate introduction to the field, we shall discuss various classification results, before we provide results on the computation of Euler characteristics. This will be the starting point for an examination of more involved invariants and further techniques. In particular, we shall discuss the Hopf conjectures, related decomposition results like the Wilhelm conjecture, results in differential topology and index theory as well as in rational homotopy theory, geometrically formal metrics in positive curvature and much more. The results we present will be discussed for arbitrary dimensions, but also specified to small dimensions. This survey article features mainly depictions of our own work interest in this area and cites results obtained in different collaborations; full statements and proofs can be found in the respective original research articles.

关键词： Positive sectional curvature torus actions Euler characteristic Hopf conjecture index theory Wilhelm conjecture geometric formality

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Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system:implications for neurorepair in the ischemic brain

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Neural Regeneration Research 2020年第4期15卷 620-624页

作者： manuel Yepes Division of Neuropharmacology and Neurologic Diseases Yerkes National Primate Research Center Department of Neurology Emory University School of Medicine Department of Neurology Veterans Affairs Medical Center

The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of ***,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled ***,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic *** ischemia has a harmful effect on synaptic structure associated with the development of functional *** agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic ***,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic *** plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of ***,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin ***-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and *** role of uPA is the brain is not fully ***,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of ***,following an ischemic injury to the mature brain the expressio

关键词： cerebral ischemia neurorepair plasminogen plasticity stoke synapse urokinase urokinase receptor

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Meiotic abnormalities in metaphase I human spermatocytes from infertile males： frequencies, chromosomes involved, and relationship with polymorphic karyotype and seminal parameters

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Asian Journal of Andrology 2014年第6期16卷 838-844页

作者： Zaida Sarrate Francesca Vidal Joan blanco Unitat de Biologia Cel.lular Facultat de Biociencies Universitat Autonoma de Barcelona Bellaterra (Cerdanyola del Valles) 08193 Spain.

The aim of this study was to look in depth at the relationship between meiotic anomalies and male infertility, such as the determination of the chromosomes involved or the correlation with patient features. For this purpose, a total of 31 testicular tissue samples from individuals consulting for fertility problems were analyzed. Metaphase I cells were evaluated using a sequential methodology combining Leishman stained procedures and multiplex fluorescence in situ hybridization protocols. The number of chromosomal units and chiasmata count per bivalent were established and a hierarchical cluster analysis of the individuals was performed. The relationship of the seminogram and the karyotype over recombination were evaluated using Poisson regression models. Results obtained in this study show a significant percentage of infertile individuals with altered meiotic behavior, mostly specified as a reduction in chiasmata count in medium and large chromosomes, the presence of univalents, and the observation of tetraploid metaphases. Moreover, the number and the type of anomalies were found to be different between cells of the same individual, suggesting the coexistence of cell lines with normal meiotic behavior and cell lines with abnormalities. In addition, chromosomal abnormalities in metaphase I are significantly associated with oligozoospermia and/or polymorphic karyotype variants.

关键词： chiasmata count human spermatocytes multiplex fluorescence in situ hybridization polymorphic karyotype seminalparameters

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Study on inverter fault-tolerant operation of PMSM DTC

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2008年第2期9卷 156-164页

作者： Yznaga blanco IVONNE Dan SUN Yi-kang HE School of Electrical Engineering Zhejiang University Hangzhou 310027 China Researches and Electrical Tests Center Cujae University Havana City 19390 Cuba

This paper presents an investigation of inverter fault-tolerant operation for a permanent magnet synchronous motor （PMSM） direct torque control （DTC） system under various inverter faults. The performance of a faulty standard 6-switch inverter driven PMSM DTC system is analyzed. To avoid the loss or even disaster caused by the inverter faults, a topology-modified inverter with fault-tolerant capability is introduced, which is reconfigured as a 3-phase 4-switch inverter. The modeling of the 4-switch inverter is then analyzed and a novel DTC strategy with a unique nonlinear perpendicular flux observer and feedback compensation scheme is proposed for obtaining a continuous, disturbance-flee drive system. The simulation and experimental results demonstrate that the proposed inverter fault-tolerant PMSM DTC system is able to operate stably and continuously with acceptable static and pretty good dynamic performance.

关键词： Permanent magnet synchronous motor (PMSM) Direct torque control (DTC) Fault-tolerant operation Four-switchinverter Nonlinear perpendicular flux observer

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Some Open Problems Related to Creative Telescoping

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Journal of Systems Science & Complexity 2017年第1期30卷 154-172页

作者： CHEN Shaoshi KAUERS manuel Key Laboratory of Mathematics Mechanization Academy of Mathematics and Systems ScienceChinese Academy of Sciences Institute for Algebra J. Kepler University Linz

Creative telescoping is the method of choice for obtaining information about definite sums or integrals. It has been intensively studied since the early 1990s, and can now be considered as a classical technique in computer algebra. At the same time, it is still a subject of ongoing *** paper presents a selection of open problems in this context. The authors would be curious to hear about any substantial progress on any of these problems.

关键词： Computer algebra creative telescoping differential algebra linear operators ore algebras symbolic integration symbolic summation.

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Clinical significance of"anti-HBc alone"in human immunodeficiency virus-positive patients

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World Journal of Gastroenterology 2009年第10期15卷 1237-1241页

作者： M~aTeresa Pérez-Rodríguez Bernardo Sopea manuel Crespo Alberto Rivera Teresa González del blanco Antonio Ocampo César Martínez-Vázquez Infectious Diseases Unit Internal Medicine DepartmentXeral-Cíes University Hospital36204 VigoSpain Faculty of Medicine University of Santiago de Compostela15705 Santiago de CompostelaA CoruaSpain Infectious Diseases Department Vall d' Hebron Hospital08035 BarcelonaSpain Microbiology Department Xeral-Cíes University Hospital36204 VigoSpain

AIM： TO determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection （“anti-HBc alone”） among human immunodeficiency virus （HIV） type-1 infected patients. Occult hepatitis B infection frequency was also evaluated. METHODS： Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus （HBV） infection were classified into three groups： past hepatitis, ＂anti-HBc alone＂ and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus （HCV） were performed on ＂anti-HBc alone＂ patients. RESULTS： One hundred and eighty seven （53.7%） HIV-positive patients had markers of HBV infection： 118 past infection （63.1%）, 14 chronic hepatitis （7.5%） and 55 ＂anti-HBc alone＂（29.4%）. Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals （Cl） 1.33-4.00] and antibodies to HCV infection [odds ratio （OR） 2.87; 95% CI 1.10-7.48] were factors independently associated with the ＂anti-HBc alone＂ pattern. No differences in liver disease frequency were detected between both groups. Serum levels of anti-HBs were not associated with HCV infection （nor viral replication or HCV genotype）, or with HIV replication or CD4 level. No ＂anti-HBc alone＂ patient tested positive for HBV DNA. CONCLUSION：＂Anti-HBc alone＂ prevalence in HIM- positive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury,

关键词： Human immunodeficiency virus "Anti-HBcalone" Occult hepatitis Hepatitis B virus DNA Liverdisease

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Acoustic streaming and Sun's meridional circulation

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Research in Astronomy and Astrophysics 2016年第9期16卷 101-106页

作者： Jose manuel Valverde Faculty of Physics University of Seville

A vast number of physical processes involving oscillations of a bounded viscous fluid are relevantly influenced by acoustic streaming. When this happens a steady circulation of fluid develops in a thin boundary adjacent to the interface. Some examples are refracted sound waves, a fluid inside a spherical cavity undergoing torsional oscillations or a pulsating liquid droplet. Steady streaming around circular interfaces consists of a hemispherically symmetric recirculation of fluid from the equatorial plane to the polar axes closely resembling the meridional circulation pattern observed in the Sun＇s convection zone that determines the solar cycle. In this paper, it is argued that the acoustic pulsations exhibited by the Sun would lead to acoustic streaming in the boundary of the convection zone. A simple estimation using a typical dominant frequency of 3 mHz and the observed surface oscillation amplitude yields a steady streaming velocity Us - 10 m s^-1, which is on the order of the meridional circulation velocity observed in the Sun＇s convection zone.

关键词： Sun general -- Sun helioseismology -- Sun granulation -- Sun oscillations -- Sun fun-damental parameters -- Sun activity

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Models and observations of sunspot penumbrae

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Science China(Physics,Mechanics & Astronomy) 2009年第11期52卷 1670-1677页

作者： BORRERO Juan manuel Max Planck Institut fr Sonnensystemforschung Max Planck Strasse 2 D 37191 Katlenburg-Lindau Germany

The mysteries of sunspot penumbrae have been under an intense scrutiny for the past 10 years. During this time, some models have been proposed and refuted, while the surviving ones had to be modified, adapted and evolved to explain the ever-increasing array of observational constraints. In this contribution I will review two of the present models, emphasizing their contributions to this field, but also pinpointing some of their inadequacies to explain a number of recent observations at very high spatial resolution (0.32 ). To help explaining these new observations I propose some modifications to each of those models. These modifications bring those two seemingly opposite models closer together into a general picture that agrees well with recent 3D magneto-hydrodynamic simulations.

关键词： sunspots magnetic fields spectropolarimetry magnetohydrodynamics

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Sperm subpopulations in avian species： a comparative study between the rooster （Gallus domesticus） and Guinea fowl （Numida meleagris）

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Asian Journal of Andrology 2016年第6期18卷 889-894页

作者： manuel Garcia-Herreros National Secretariat of Higher Education Science Technology and Innovation (SENESCYT) Quito Ecuador

The main aims of this research were to study possible differences in objective morphometric sperm characteristics, establish normative sperm morphometry standards, and evaluate the presumed different subpopulation distribution of avian spermatozoa from the rooster （Gallus domesticus） and Guinea fowl （Numida meleagris） as model avian species. Seventy-two ejaculates （36 per species studied） were obtained manually, following a training period involving gently combined dorso-abdominal and *** massage of the birds. Ejaculates were processed for volume, sperm concentration, viability, motility, and morphology. Moreover, samples were submitted for sperm morphometric assessment using objective Computer-Assisted Semen Analysis for Morphometry （CASA-Morph） methods, with sperm morphometric descriptors evaluated by Principal Component Analysis （PCA） and multivariate clustering analyses. There were several differences observed between the avian species in values obtained for ejaculate volume and sperm concentration （P 〈 0.001）. Irrespective of species, PCA revealed two Principal Components （PCs） explaining more than 80% of the variance. In addition, the number of subpopulations differed with species （three and five subpopulations for rooster and Guinea fowl, respectively）. Moreover, the distribution of the sperm subpopulations was found to be structurally different between species. In conclusion, our findings from using CASA-Morph methods indicate pronounced sperm morphometric variation between these two avian species. Because of the strong differences observed in morphometric parameter values and their subpopulation distribution, these results suggest that application of objective analytical methods such as CASA-Morph could substantially improve the reliability of comparative studies and help establish valid normative sperm morphological values for avian species.

关键词： Gallus domesticus Numida meleaEris principal component analysis sperm morphometry sperm subpopulations

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