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Targeting TrkB–pSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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The theory of interaction between wave and basic flow

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Chinese physics B 2008年第3期17卷 1138-1146页

作者：冉令坤 john p.Boyd Laboratory of Cloud-precipitation physics and Severe Storms (LACS) Institute of Atmospheric PhysicsChinese Academy of Sciences Department of Atmospheric Oceanicand Space ScienceUniversity of MichiganAnn ArborMichiganUSA

This paper investigates the interaction between transient wave and non-stationary and non-conservative basic flow. An interaction equation is derived from the zonally symmetric and non-hydrostatic primitive equations in Cartesian coordinates by using the Momentum-Casimir method. In the derivation, it is assumed that the transient disturbances satisfy the linear perturbation equations and the basic states are non-conservative and slowly vary in time and space. The diabatic heating composed of basic-state heating and perturbation heating is also introduced. Since the theory of wave-flow interaction is constructed in non-hydrostatic and ageostrophic dynamical framework, it is applicable to diagnosing the interaction between the meso-scale convective system in front and the background flow. It follows from the local interaction equation that the local tendency of pseudomomentum wave-activity density depends on the combination of the perturbation flux divergence second-order in disturbance amplitude, the local change of basic-state pseudomomentum density, the basic-state flux divergence and the forcing effect of diabatic heating. Furthermore, the tendency of pseudomomentum wave-activity density is opposite to that of basic-state pseudomomentum density. The globally integrated basic-state pseudomomentum equation and wave-activity equation reveal that the global development of basic-state pseudomomentum is only dominated by the basic-state diabatic heating while it is the forcing effect of total diabatic heating from which the global evolution of pseudomomentum wave activity results. Therefore, the interaction between the transient wave and the non-stationary and non-conservative basic flow is realized in virtue of the basic-state diabatic heating.

关键词： wave flow interaction pseudomomentum wave activity diabatic heating Momentum Casimir method

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Energy Gap Dependence on Mn Content in a Diluted Magnetic Quantum Dot

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Chinese physics Letters 2011年第4期28卷 201-204页

作者： p.Nalini A.john peter Department of physics Yadava College Govindarajan CampusThiruppalaiMadurai-625014India Department of physics Govt.Arts and Science CollegeMelur-625106MaduraiIndia

positively charged donor exciton binding energy is computed as a function of quantum-dot size within the single band effective mass approximation for different Mn contents in Cd_(1)−x_(𝑥in)Mn_(x𝑥in)Te/Cd_(1−xout)𝑥outMn_(xout)𝑥*** exciton bound polaron is computed for 0≤x𝑥≤0.08,on the Mn mole *** determine the energy gap using the mean field approximation and incorporate the exchange interaction between the carrier and the magnetic *** interband emission energy is studied with the height and radius of the cylindrical quantum ***-band anisotropy is included in our theoretical model using different hole masses in different spatial *** polaronic shifts as functions of quantum-dot radius and Mn concentration are estimated using the mean field *** is found that(i)the energy gap depends on the Mn mole fraction,(ii)it increases linearly with an increase in Mn content,and(iii)the effect is more pronounced for a narrow dot,showing the quantum size *** results are in good agreement with other recently published reports.

关键词： theory quantum radius

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A Method of Characterizing Radio Signal Space for Wireless Device Localization

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Tsinghua Science and Technology 2015年第4期20卷 385-408页

作者： john-Austen Francisco Richard p.Martin Department of Computer Science Rutgers University

In this work we present a novel approach for describing radio signal spaces for localization algorithms. We first introduce a new metric, the Discretely Distributed Log-H61der Metric （DDLHM）. The DDLHM is designed to characterize the type and degree of signal distortion relative to Iognormal signal-to-distance path models. We first show how the DDLHM can describe and discriminate distortions in an exhaustive set of synthetic signal spaces. We then determine a reduced set of maximally diagnostic distortion parameters. Using only 4% of the maximal set of DDLHMs, we found the reduced set matches with an acceptable degree of error 95% of the time. Using the synthetic reduced set, we characterized a variety of wireless localization algorithms＇ behaviors to attenuation, bias, and multipath. We found algorithms made much different tradeoffs between best case and average case error. We then use the DDLHM to identify distortion types in three different physical environments using measured 802.11 signal strengths, and predict the positioning performance of several localization algorithms. Our approach predicts average localization error to within 2 meters of the observed average error.

关键词： radio propgation 802.11 WiFi

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Chebyshev Spectral Methods and the Lane-Emden problem

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Numerical Mathematics(Theory,Methods and Applications) 2011年第2期4卷 142-157页

作者： john p.Boyd Department of Atmospheric Oceanic and Space ScienceUniversity of Michigan2455 Hayward AvenueAnn ArborMI 48109-2143USA

The three-dimensional spherical polytropic Lane-Emden problem is yr r+(2/r)y_(r)+y^(m)=0,y(0)=1,y_(r)(0)=0 where m∈[0,5]is a constant *** domain is r∈[0,ξ]whereξis the first root of y(r).We recast this as a nonlinear eigenproblem,with three boundary conditions andξas the eigenvalue allowing imposition of the extra boundary condition,by making the change of coordinate x≡r/ξ:y_(xx)+(2/x)y_(x)+ξ^(2) y^(m)=0,y(0)=1,y_(x)(0)=0,y(1)=*** find that a Newton-Kantorovich iteration always converges from an m-independent starting point y^((0))(x)=cos([π/2]x),ξ^((0))=*** apply a Chebyshev pseudospectral method to discretize *** Lane-Emden equation has branch point singularities at the endpoint x=1 whenever m is not an integer;we show that the Chebyshev coefficients are a_(n)∼constant/n^(2m+5) as n→∞.However,a Chebyshev truncation of N=100 always gives at least ten decimal places of accuracy—much more accuracy when m is an *** numerical algorithm is so simple that the complete code(in Maple)is given as a one page table.

关键词： Lane-Emden Chebyshev polynomial pseudospectral

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A Fourier Companion Matrix (Multiplication Matrix) with Real-Valued Elements: Finding the Roots of a Trigonometric polynomial by Matrix Eigensolving

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Numerical Mathematics(Theory,Methods and Applications) 2013年第4期6卷 586-599页

作者： john p.Boyd Department of Atmospheric Oceanic&Space ScienceUniversity of Michigan2455 Hayward AvenueAnn Arbor MI 48109USA

We show that the zeros of a trigonometric polynomial of degree N with the usual(2N+1)terms can be calculated by computing the eigenvalues of a matrix of dimension 2N with real-valued elements M_(jk).This matrix M is a multiplication matrix in the sense that,after first defining a vector φwhose elements are the first 2N basis functions,Mφ=2cos(t)φ.This relationship is the eigenproblem;the zeros tk are the arccosine function of λ_(k)/2 where theλk are the eigenvalues of *** dub this the“Fourier Division Companion Matrix”,or FDCM for short,because it is derived using trigonometric polynomial *** show through examples that the algorithm computes both real and complex-valued roots,even double roots,to near machine precision accuracy.

关键词： Fourier series trigonometric polynomial rootfinding secular companion matrix

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Impact of androgen deprivation therapy on sexua function

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Asian Journal of Andrology 2012年第2期14卷 198-203页

作者： clarisse R Mazzola john p Mulhall Sexual and Reproductive Medicine program Urology ServiceMemorial SIoan Kettering Cancer CenterNew YorkNY 10065USA

Many patients with prostate cancer for whom androgen deprivation therapy （ADT） is indicated are young and desire to remain sexually active. In such patients, the side effects of androgen therapy on sexual function can be a source of serious reduction in overall quality of life. providing the appropriate treatment options in this patient population is therefore essential. Nevertheless, treating such patients is challenging and an understanding of the underlying mechanisms of sexual physiology and pathophysiology is crucial to optimal patient care. In this paper, we reviewed what was known regarding the effects of ADT on sexual function in animal models and we also provided a detailed review on the effects of ADT on sexual health in humans and its treatment.

关键词： androgen deprivation therapy castration ejaculation erectile dysfunction orgasm

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Asymptotic coefficients and errors for Chebyshev polynomial approximations with weak endpoint singularities: Effects of different bases

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Science China Mathematics 2023年第1期66卷 191-220页

作者： Xiaolong Zhang john p.Boyd MOE-LCSM School of Mathematics and StatisticsHunan Normal UniversityChangsha 410081China Department of Climate&Space Sciences and Engineering University of MichiganAnn ArborMI 48109USA

When one solves differential equations by a spectral method,it is often convenient to shift from Chebyshev polynomials Tn(x) with coefficients anto modified basis functions that incorporate the boundary *** homogeneous Dirichlet boundary conditions,u(±1)=0,popular choices include the "Chebyshev difference basis" ζn(x)≡Tn+2(x)-Tn(x) with coefficients here denoted by bnand the "quadratic factor basis" Qn(x)≡(1-x2)Tn(x) with coefficients *** u(x) is weakly singular at the boundary,then the coefficients andecrease proportionally to O(A(n)/nκ) for some positive constant κ,where A(n) is a logarithm or a *** prove that the Chebyshev difference coefficients bndecrease more slowly by a factor of 1/n while the quadratic factor coefficients cndecrease more slowly still as O(A(n)/nκ-2).The error for the unconstrained Chebyshev series,truncated at degree n=N,is O(|A(N)|/Nκ) in the interior,but is worse by one power of N in narrow boundary layers near each of the *** having nearly identical error norms in interpolation,the error in the Chebyshev basis is concentrated in boundary layers near both endpoints,whereas the error in the quadratic factor and difference basis sets is nearly uniformly oscillating over the entire interval in ***,for Chebyshev polynomials,the values of their derivatives at the endpoints are O(n2),but only O(n) for the difference ***,we give the asymptotic coefficients and rigorous error estimates of the approximations in these three bases,solved by the least squares *** also find an interesting fact that on the face of it,the aliasing error is regarded as a bad thing;actually,the error norm associated with the downward curving spectral coefficients decreases even faster than the error norm of infinite *** the premise is under the same basis,and when involving different bases,it may not be established yet.

关键词： Chebyshev polynomial interpolation endpoint singularities least squares method

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Reliability-based design in rock engineering: Application of Bayesian regression methods to rock strength data

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Journal of Rock Mechanics and Geotechnical Engineering 2019年第3期11卷 612-627页

作者： Nezam Bozorgzadeh john p.Harrison Department of Civil Engineering GeoEngineering Centre at Queen’s-RMC(Royal Military College of Canada)KingstonCanada Department of Civil and Mineral Engineering University of TorontoTorontoCanada

Reliability-based design (RBD) is being adopted by geotechnical design codes worldwide, and it is therefore necessary that rock engineering practice evolves to embrace RBD. This paper examines the Hoek-Brown (H-B) strength criterion within the RBD framework, and presents three distinct analyses using a Bayesian approach. Firstly, a compilation of intact compressive strength test data for six rock types is used to examine uncertainty and variability in the estimated H-B parameters m and σc, and corresponding predicted axial strength. The results suggest that within- and between-rock type variabilities are so large that these parameters need to be determined from rock testing campaigns, rather than reference values being used. The second analysis uses an extensive set of compressive and tensile (both direct and indirect) strength data for a granodiorite, together with a new Bayesian regression model, to develop joint probability distributions of m and σc suitable for use in RBD. This analysis also shows how compressive and indirect tensile strength data may be robustly used to fit an H-B criterion. The third analysis uses the granodiorite data to investigate the important matter of developing characteristic strength criteria. Using definitions from Eurocode 7, a formal Bayesian interpretation of characteristic strength is proposed and used to analyse strength data to generate a characteristic criterion. These criteria are presented in terms of characteristic parameters mk and σck, the values of which are shown to depend on the testing regime used to obtain the strength data. The paper confirms that careful use of appropriate Bayesian statistical analysis allows the H-B criterion to be brought within the framework of RBD. It also reveals that testing guidelines such as the International Society for Rock Mechanics and Rock Engineering (ISRM) suggested methods will require modification in order to support RBD. Importantly, the need to fully understand the implications of

关键词： Reliability-based design(RBD) Hoek-Brown(HeB)criterion Bayesian regression Indirect tensile strength Characteristic strength criterion

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A statistical study of the interdependence of solar wind parameters

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Chinese Journal of Astronomy and Astrophysics 2009年第4期9卷 485-493页

作者： Shollykutty john p. J. Kurian Department of physics St Joseph’s CollegeAlappuzha.Kerala-688012 India physics Research Centre St.Berchmans’ CollegeChanganacherry Kerala-686101 India

Correlation analysis of solar wind parameters, namely solar wind velocity, proton density, proton temperature and mean interplanetary magnetic field （IMF） from the ACE spacecraft data near Earth, was done. To our best knowledge, this study is a novel one since we consider here only the parameters inside the solar wind, including the mean IMF and, hence, the solar wind is a self consistent system. We have proposed a Multiple Linear Regression （MLR） model for the prediction of the response variable （solar wind velocity） using the parameters proton density, proton temperature and mean IMF measured as daily averages. About 60% of the observed value can be predicted using this model. It is shown that, in general, the correlation between solar wind parameters is significant. A deviation from the prediction at the solar maximum is interpreted. These results are verified by a graphical method.

关键词： solar wind-statistical model-correlation-solar wind parameters

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