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Brain endothelial cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in aging and neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 2005-2007页

作者： Bryan Sun Lulin Li Jian Luo Palo Alto Veterans Institute for Research VA Palo Alto Health Care SystemPalo AltoCAUSA Polytrauma System of Care VA Palo Alto Health Care SystemPalo AltoCAUSA

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of *** current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial ***,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic ***,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.

关键词： stimulator interferon inflammation

A novel method for clustering cellular data to improve classification

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Neural Regeneration Research 2025年第9期20卷 2697-2705页

作者： Diek W.Wheeler Giorgio A.Ascoli Center for Neural Informatics Structures&PlasticityKrasnow Institute for Advanced Study Bioengineering Department Volgenau School of Engineering George Mason University FairfaxVAUSA

Many fields,such as neuroscience,are experiencing the vast prolife ration of cellular data,underscoring the need fo r organizing and interpreting large datasets.A popular approach partitions data into manageable subsets via hierarchical clustering,but objective methods to determine the appropriate classification granularity are *** recently introduced a technique to systematically identify when to stop subdividing clusters based on the fundamental principle that cells must differ more between than within *** we present the corresponding protocol to classify cellular datasets by combining datadriven unsupervised hierarchical clustering with statistical *** general-purpose functions are applicable to any cellular dataset that can be organized as two-dimensional matrices of numerical values,including molecula r,physiological,and anatomical *** demonstrate the protocol using cellular data from the Janelia MouseLight project to chara cterize morphological aspects of neurons.

关键词： cellular data clustering dendrogram data classification Levene's one-tailed statistical test unsupervised hierarchical clustering

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针灸的神经生物学机理

中华中医药杂志 2018年第10期33卷 4281-4297页

作者：潘卫星 Janelia Research Campus Howard Hughes Medical Institute Ashburn VA 20147 USA

"针刺感受处,疾病反应所,治疗作用点"是腧穴的三大功能,也是理解针灸作用原理的基本点。现代研究表明:(1)穴位感针现象的实质是神经感受。针刺激动不同类型的神经成分而产生针感。不同针法(刺激形式和刺激量)可激动不同类型和数量的外... 详细信息

"针刺感受处,疾病反应所,治疗作用点"是腧穴的三大功能,也是理解针灸作用原理的基本点。现代研究表明:(1)穴位感针现象的实质是神经感受。针刺激动不同类型的神经成分而产生针感。不同针法(刺激形式和刺激量)可激动不同类型和数量的外周神经,从而引起性质、范围、时间上各异的调节效应。阻断支配穴区的神经可取消针感和针效,而刺激外周神经可模拟针效,表明神经系统是介导针效的充分必要条件。因而穴位是相对的,体表可以施针的位点与数量不限于经典穴。(2)穴位应病现象的机制是脊髓同节段和脊神经节同神经元支配的内脏-躯体相关的神经元性炎症敏化过程。对于内脏病症,体表敏化点是可资选择的靶向精准的活化穴。(3)针疗作用的三个基本特点是:针灸的作用性质属机能调节,通过激励自愈力而获效;穴位作用范围具有选择性调节和泛调节双重效应,分别通过局部微创、轴突反射、脊髓节段支配、脑内整合及脑输出等五级效应途径实现;针灸的调节方式呈双向性调衡效应,以机体稳态自动控制和适应性调节为基础。大量生物学实验已为揭开这些针灸作用之谜提供了多层次多角度的考察与阐释,并为提高临床疗效提供了新的途径和启示。总结既往丰富的研究结果,不难看到,针灸机理的系统性构架已经呈现,正逐步走向成熟。

关键词：针灸穴位针灸机理针刺双向调节外周神经刺激

Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury:a cross-sectional pilot study

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Neural Regeneration Research 2021年第12期16卷 2486-2493页

作者： Mina P.Ghatas M.Rehan Khan Ashraf S.Gorgey Department of Spinal Cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Radiology Hunter Holmes McGuire VA Medical CenterRichmondVAUSA Department of Physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA

Skeletal muscle stiffness is altered after spinal cord injury(SCI).Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after *** study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size,spasticity,and peak torque in persons with *** studies examined the association between muscle stiffness and spasticity,however,we are unaware of other studies that examined the effects of muscle composition on stiffness after *** participants(one female)with chronic SCI and eight(one female)matched able-bodied controls participated in this cross-sectional *** resonance elastography was utilized to monitor stiffness derived from shear waves *** Ashworth scale was used to evaluate spasticity scores in a blinded *** isometric and isokinetic torques were measured using a biodex *** values were non-significantly lower(12.5%;P=0.3)in the SCI group compared to able-bodied ***,stiffness was positively related to vastus lateralis whole muscle cross-sectional area(CSA)(r2=0.64,Pvastus lateralis absolute muscle CSA after accounting for intramuscular fat(r2=0.78,P<0.0007).Stiffness was also positively correlated to both isometric(r2=0.55-0.57,P<0.05)and isokinetic peak(r2=0.46-0.48,P<0.05)*** results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy *** appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed *** preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular *** study procedures were approved by the Institutional Review Board at the

关键词： chronic spinal cord injury isometric and isokinetic torques magnetic resonance elastography muscle size rehabilitation shear modulus spasticity stiffness

Executive functioning in TBI from rehabilitation to social reintegration: COMPASS^(goal), a randomized controlled trial(grant: 1I01RX000637-01A3 by the va ORD RR&D, 2013–2016)

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Military Medical Research 2015年第4期3卷 181-200页

作者： Alexander V.Libin Joel Scholten Manon Maitland Schladen Ellen Danford Nawar Shara Walter Penk Jordan Grafman Linda Resnik Dwan Bruner Samantha Cichon Miriam Philmon Brenda Tsai Marc Blackman Alexander Dromerick Mental Health Service Washington DC VA Medical Center Med Star National Rehabilitation Hospital Med Star Health Research Institute Physical Medicine and Rehabilitation Service Washington DC VA Medical Center Research Service Washington DC VA Medical Center Texas A&M College of Medicine Rehabilitation Institute of Chicago Research Service Providence VA Medical Center

Background: Traumatic brain injury is a major health problem that frequently leads to deficits in executive function. Self-regulation processes, such as goal-setting, may become disordered after traumatic brain injury, particularly when the frontal regions of the brain and their connections are involved. Such impairments reduce injured veterans' ability to return to work or school and to regain satisfactory personal lives. Understanding the neurologically disabling effects of brain injury on executive function is necessary for both the accurate diagnosis of impairment and the individual tailoring of rehabilitation processes to help returning service members recover independent ***/design: The COMPASSgoal(Community Participation through Self-Efficacy Skills Development) program develops and tests a novel patient-centered intervention framework for community reintegration psychosocial research in veterans with mild traumatic brain injury. COMPASSgoal integrates the principles and best practices of goal self-management. Goal setting is a core skill in self-management training by which persons with chronic health conditions learn to improve their status and decrease symptom effects. Over a three-year period, COMPASSgoal will recruit 110 participants with residual executive dysfunction three months or more post-injury. Inclusion criteria combine both clinical diagnosis and standardized scores that are >1 SD from the normative score on the Frontal Systems Rating Scale. Participants are randomized into two groups: goal-management(intervention) and supported discharge(control). The intervention is administered in eight consecutive, weekly sessions. Assessments occur at enrollment, post-intervention/supported discharge, and three months post-treatment ***: Goal management is part of the "natural language" of rehabilitation. However, collaborative goal-setting between clinicians/case managers and clients can be hindered by the cognitive deficits

关键词： Executive function Traumatic brain injury Goal-setting Community reintegration Veterans Randomized controlled trial Manualized psychosocial intervention

Phase classification of multi-principal element alloys via interpretable machine learning

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npj Computational Materials 2022年第1期8卷 206-217页

作者： Kyungtae Lee Mukil V.Ayyasamy Paige Delsa Timothy Q.Hartnett Prasanna V.Balachandran Department of Materials Science and Engineering University of VirginiaCharlottesvilleVA22904USA Department of Physics University of RichmondRichmondVA23173USA Department of Mechanical and Aerospace Engineering University of VirginiaCharlottesvilleVA22904USA

There is intense interest in uncovering design rules that govern the formation of various structural phases as a function of chemical composition in multi-principal element alloys (MPEAs).In this paper,we develop a machine learning (ML) approach built on the foundations of ensemble learning,post hoc model interpretability of black-box models,and clustering analysis to establish a quantitative relationship between the chemical composition and experimentally observed phases of *** originality of our work stems from performing instance-level (or local) variable attribution analysis of ML predictions based on the breakdown method,and then identifying similar instances based on k-means clustering analysis of the breakdown *** also complement the breakdown analysis with Ceteris Paribus profiles that showcase how the model response changes as a function of a single variable,when the values of all other variables are *** from local model interpretability analysis uncover key insights into variables that govern the formation of each *** developed approach is generic,model-agnostic,and valuable to explain the insights learned by the black-box *** interactive web application is developed to facilitate model sharing and accelerate the design of MPEAs with targeted properties.

关键词： alloys element instance

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer＇s disease

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Neural Regeneration Research 2018年第1期13卷 19-25页

作者： Isaac G. Onyango Gertcia Biotechnology Charlottesville VA USA

Alzheimer’s disease （AD） is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

关键词： Alzheimer's disease mitochondria bioenergetics mitochondrial DNA neuroinflammation mitohormesis caloric restriction hypometabolism mitophagy mitochondrial biogenesis recombinant-human mitochondrial transcription factor A antioxidants proteasome mitochondrial transcription activator-like effector nucleases clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) caloric restriction stem cells

Generating synthetic as-built additive manufacturing surface topography using progressive growing generative adversarial networks

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Friction 2024年第6期12卷 1283-1298页

作者： Junhyeon SEO Prahalada RAO Bart RAEYMAEKERS Department of Mechanical Engineering Virginia TechBlacksburgVA 24061USA Grado Department of Industrial and Systems Engineering Virginia TechBlacksburgVA 24061USA

Numerically generating synthetic surface topography that closely resembles the features and characteristics of experimental surface topography measurements reduces the need to perform these intricate and costly ***,existing algorithms to numerically generated surface topography are not well-suited to create the specific characteristics and geometric features of as-built surfaces that result from laser powder bed fusion(LPBF),such as partially melted metal particles,porosity,laser scan lines,and ***,we present a method to generate synthetic as-built LPBF surface topography maps using a progressively growing generative adversarial *** qualitatively and quantitatively demonstrate good agreement between synthetic and experimental as-built LPBF surface topography maps using areal and deterministic surface topography parameters,radially averaged power spectral density,and material ratio *** ability to accurately generate synthetic as-built LPBF surface topography maps reduces the experimental burden of performing a large number of surface topography ***,it facilitates combining experimental measurements with synthetic surface topography maps to create large data-sets that facilitate,*** as-built surface topography to LPBF process parameters,or implementing digital surface twins to monitor complex end-use LPBF parts,amongst other applications.

关键词： additive manufacturing surface topography synthetic surface topography generative adversarial networks

Numerical three-dimensional modeling of earthen dam piping failure

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Water Science and Engineering 2024年第1期17卷 72-82页

作者： Zhengang Wang Independent Researcher HerndonVA 20171USA

A physically-based numerical three-dimensional earthen dam piping failure model is developed for homogeneous and zoned soil *** model is an erosion model,coupled with force/moment equilibrium *** flow and two-dimensional(2D)shallow water equations(SWE)are solved to simulate dam break flows at different breaching *** rates of different soils with different construction compaction efforts are calculated using corresponding erosion *** dam's real shape,soil properties,and surrounding area are *** outer 2D-SWE grids are used to control upstream and downstream hydraulic conditions and control the boundary conditions of orifice flow,and inner 2D-SWE flow is used to scour soil and perform force/moment equilibrium *** model is validated using the European Commission IMPACT(Investigation of Extreme Flood Processes and Uncertainty)Test#5 in Norway,Teton Dam failure in Idaho,USA,and Quail Creek Dike failure in Utah,*** calculated peak outflows are within 10%errors of observed *** results show that,for a V-shaped dam like Teton Dam,a piping breach location at the abutment tends to result in a smaller peak breach outflow than the piping breach location at the dam's center;and if Teton Dam had broken from its center for internal erosion,a peak outflow of 117851 m'/s,which is 81%larger than the peak outflow of 65120 m3/s released from its right abutment,would have been released from Teton Dam.A lower piping inlet elevation tends to cause a faster/earlier piping breach than a higher piping inlet elevation.

关键词： 3D dam breach model 2D shallow water equations 3D slope stability analysis Piping failure Teton Dam Quail Creek Dike