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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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Near-field terahertz nonlinear optics with blue light

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Light(Science & Applications) 2023年第5期12卷 838-846页

作者： Angela Pizzuto Pingchuan Ma Daniel M.Mittleman Department of Physics Brown UniversityProvidence RI 02912USA School of Engineering Brown UniversityProvidence RI 02912USA

The coupling of terahertz optical techniques to scattering-type scanning near-field microscopy(s-SNOM)has recently emerged as a valuable new paradigm for probing the properties of semiconductors and other materials on the *** have demonstrated a family of related techniques,including terahertz nanoscopy(elastic scattering,based on linear optics),time-resolved methods,and nanoscale terahertz emission ***,as with nearly all examples of s-SNOM since the technique’s inception in the mid-1990s,the wavelength of the optical source coupled to the near-field tip is long,usually at energies of 2.5 eV or *** in coupling of shorter wavelengths(i.e.,blue light)to the nanotip has greatly inhibited the study of nanoscale phenomena in wide bandgap materials such as Si and ***,we describe the first experimental demonstration of s-SNOM using blue *** femtosecond pulses at 410 nm,we generate terahertz pulses directly from bulk silicon,spatially resolved with nanoscale resolution,and show that these signals provide spectroscopic information that cannot be obtained using near-infrared *** develop a new theoretical framework to account for this nonlinear interaction,which enables accurate extraction of material *** work establishes a new realm of possibilities for the study of technologically relevant wide-bandgap materials using s-SNOM methods.

关键词： scattering optics nonlinear

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Microparticles with tunable,cell-like properties for quantitative acoustic mechanophenotyping

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Microsystems & Nanoengineering 2023年第4期9卷 129-141页

作者： Ryan Dubay Eric MDarling Jason Fiering Center for Biomedical Engineering Brown UniversityProvidenceRI 02912USA Biological Microsystems DraperCambridgeMA 02139USA Department of Pathology and Laboratory Medicine Brown UniversityProvidenceRI 02912USA School of Engineering Brown UniversityProvidenceRI 02912USA Department of Orthopaedics Brown UniversityProvidenceRI 02912USA

Mechanical properties of biological cells have been shown to correlate with their biomolecular state and function,and therefore methods to measure these properties at scale are of *** microfluidic technologies can measure the mechanical properties of cells at rates over 20,000 cells/s,which is more than four orders of magnitude faster than conventional ***,precise and repeatable means to calibrate and test these new tools remain lacking,since cells themselves are by nature ***,microfluidic tools use rigid polymer microspheres for calibration because they are widely available in cell-similar sizes,but conventional microspheres do not fully capture the physiological range of other mechanical properties that are equally important to device function(e.g.,elastic modulus and density).Here,we present for the first time development of monodisperse polyacrylamide microparticles with both tunable elasticity and tunable *** these size,elasticity,and density tunable particles,we characterized a custom acoustic microfluidic device that makes single-cell measurements of mechanical *** then applied the approach to measure the distribution of the acoustic properties within samples of human leukocytes and showed that the system successfully discriminates lymphocytes from other *** initial demonstration shows how the tunable microparticles with properties within the physiologically relevant range can be used in conjunction with microfluidic devices for efficient high-throughput measurements of mechanical properties at single-cell resolution.

关键词： tunable elasticity function

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MICROMECHANICS OF ROUGH SURFACE ADHESION:A HOMOGENIZED PROJECTION METHOD

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Acta Mechanica Solida Sinica 2009年第5期22卷 377-390页

作者： Kyung-Suk Kim Division of Engineering Brown UniversityProvidenceRI 02912USA

A quasistatic homogenized projection is made to characterize the effective cohesive zone behavior for rough-surface adhesion. In the context of the homogenized projection, the traction versus separation relation for the homogenized cohesive zone （HCZ） of a rough interface can be highly oscillatory due to instabilities during microscopic adhesion and decohesion processes. The instabilities are found to occur not only individually but also collectively among the adhesive micro-asperity contacts, leading to extensive energy dissipation. Based on the behaviors of the HCZ relations, a framework for describing instability-induced energy dissipation in rough-surface adhesion is proposed to elucidate the effect of roughness on apparent interface adhesion. Two non- dimensional parameters, α related to roughness morphology and n related to flaw distribution, are identified to be most crucial for controlling the energy dissipation. For an interface with a shallow roughness and a strong intrinsic adhesive strength, the interface adhesion can be stronger if we make it rougher （reducing α） or lower its flaw density （increasing n）. The HCZ projection method can be potentially extended and employed to bridge the apparent adhesion from intrinsic adhesion properties for engineering surfaces with multi-scale shallow roughness.

关键词： homogenized cohesive zone interface adhesion roughness effect instability energy dissipation

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EVOLUTION OF ROUGHNESS ON THE SURFACE OF A STRAINED ELASTIC MATEriAL DUE TO STRESS-DriVEN SURFACE DIFFUSION

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Acta Mechanica Sinica 1994年第1期10卷 16-26页

作者： L.B.Freund Division of Engineering Brown University Providence RI 02912 USA

The free energy of a stressed crystal is assumed to consist of elastic strain energy and surface energy, and the chemical potential for surface diffusion at constant temperature is obtained under this assumption. A gradient in chemical potential results in diffusive mass transport along the surface. The result is applied in considering the phenomena of instability of a flat surface in a stressed material under fluctuations in surface shape, and the transient evolution of surface roughness due to an initial perturbation in the nearly flat free surface of the material, both under plane strain conditions.

关键词： elastic material surface energy diffusion

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ON THE MECHANICS OF INTEGriN CLUSTEriNG DUriNG CELL-SUBSTRATE ADHESION

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Acta Mechanica Solida Sinica 2012年第5期25卷 467-472页

作者： Hongyan Yuan Huajian Gao School of Engineering Brown University Providence RI 02912 USA

Recent numerical simulations have indicated that integrin clustering during cell- substrate adhesion can be driven by the presence of a repulsive layer between the cell membrane and the substrate （Paszek et al., PLoS Comput Biol 5：12, 2009）. Here we present a simple me- chanics model of this phenomenon in which the attraction between integrins is mediated by the long-range elastic deformation of the membrane and the repulsive layer. We obtain analytical solutions to the problem by employing the small deformation theory of an infinitely extended plate resting on an elastic foundation.

关键词： integrin clustering mechanics model cell-substrate adhesion attractive interaction

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Wave Fans are Special

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Acta Mathematicae Applicatae Sinica 2008年第3期24卷 369-374页

作者： Constantine M.Dafermos Division of Applied Mathematics Brown UniversityProvidenceRI 02912USA

It is shown that self-similar BV solutions of genuinely nonlinear strictly hyperbolic systems of conservation laws are special functions of bounded variation, with vanishing Cantor part.

关键词： Hyperbolic conservation laws self-similar solutions special functions of bounded variation

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Physics-informed neural networks(PINNs)for fluidmechanics:a review

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Acta Mechanica Sinica 2021年第12期37卷 1727-1738页

作者： Shengze Cai Zhiping Mao Zhicheng Wang Minglang Yin George Em Karniadakis Division of Applied Mathematics Brown UniversityProvidenceRI 02912USA School of Mathematical Sciences Xiamen University 361005 China Laboratory of Ocean Energy Utilization of Ministry of Education Dalian University of TechnologyDalian116024China School of Engineering Brown UniversityProvidenceRI 02912USA Center for Biomedical Engineering Brown UniversityProvidenceRI 02912USA

Despite the significant progress over the last 50 years in simulating flow problems using numerical discretization of the Navier–Stokes equations(NSE),we still cannot incorporate seamlessly noisy data into existing algorithms,mesh-generation is complex,and we cannot tackle high-dimensional problems governed by parametrized ***,solving inverse flow problems is often prohibitively expensive and requires complex and expensive formulations and new computer ***,we review flow physics-informed learning,integrating seamlessly data and mathematical models,and implement them using physics-informed neural networks(PINNs).We demonstrate the effectiveness of PINNs for inverse problems related to three-dimensional wake flows,supersonic flows,and biomedical flows.

关键词： Physics-informed learning PINNs Inverse problems Supersonic flows Biomedical flows

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Making bridges between preclinical and clinical insights into age-related cognitive decline

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Neural Regeneration Research 2025年第8期20卷 2321-2322页

作者： David VC Brito Clévio Nóbrega Algarve Biomedical Center-Research Institute(ABC-ri) Campus GambelasFaroPortugal Algarve Biomedical Center-(ABC) Campus GambelasFaroPortugal Faculty of Medicine and Biomedical Sciences(FMCB) University of AlgarveGambelas CampusFaroPortugal

With people living longer,the societal impact of age-related cognitive decline is becoming more pronounced(Crimmins,2015).Thus,it is increasingly important to comprehend the cognitive shifts linked to aging-whether th... 详细信息

关键词： bridges becoming insight

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A New Approach of High OrderWell-Balanced Finite Volume WENO Schemes and Discontinuous Galerkin Methods for a Class of Hyperbolic Systems with Source Terms

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Communications in Computational Physics 2006年第1期1卷 100-134页

作者： Yulong Xing Chi-Wang Shu Department of Mathematics Brown UniversityProvidenceRI 02912USA Division of Applied Mathematics Brown UniversityProvidenceRI 02912USA

Hyperbolic balance laws have steady state solutions in which the flux gradients are nonzero but are exactly balanced by the source *** our earlier work[31–33],we designed high order well-balanced schemes to a class of hyperbolic systems with separable source *** this paper,we present a different approach to the same purpose:designing high order well-balanced finite volume weighted essentially non-oscillatory(WENO)schemes and RungeKutta discontinuous Galerkin(RKDG)finite element *** make the observation that the traditional RKDG methods are capable of maintaining certain steady states exactly,if a small modification on either the initial condition or the flux is *** computational cost to obtain such a well balanced RKDG method is basically the same as the traditional RKDG *** same idea can be applied to the finite volume WENO *** will first describe the algorithms and prove the well balanced property for the shallow water equations,and then show that the result can be generalized to a class of other balance *** perform extensive one and two dimensional simulations to verify the properties of these schemes such as the exact preservation of the balance laws for certain steady state solutions,the non-oscillatory property for general solutions with discontinuities,and the genuine high order accuracy in smooth regions.

关键词： Hyperbolic balance laws WENO finite volume scheme discontinuous Galerkin method high order accuracy source term conservation laws shallow water equation elastic wave equation chemosensitive movement nozzle flow two phase flow

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