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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge d.miranda department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Lithium bis(trifluoromethanesulfonyl)imide blended in polyurethane acrylate photocurable solid polymer electrolytes for lithium-ion batteries

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Journal of Energy Chemistry 2021年第11期30卷 485-496,I0011页

作者： Cristian Mendes-Felipe J.C.Barbosa R.Gonsalves d.miranda C.M.Costa J.L.Vilas-Vilela S.Lanceros-Mendez BCMaterials Basque Center for MaterialsApplications and NanostructuresUPV/EHU Science Park48940 LeioaSpain Macromolecular Chemistry Group(LABQUIMAC) Department of Physical ChemistryFaculty of Science and TechnologyUniversity of the Basque Country(UPV/EHU)Barrio Sarriena s/nE-48940 LeioaSpain Center of Physics University of MinhoCampus of Gualtar4710-057 BragaPortugal Center of Chemistry University of MinhoCampus of Gualtar4710-057 BragaPortugal Ai–School of Technology IPCABarcelosPortugal Ikerbasque Basque Foundation for Science48009 BilbaoSpain

The increased demand of electronic devices promotes the development of advanced and more efficient energy storage devices, such as batteries. Lithium-ion batteries (LIBs) are the most studied battery systems due to their high performance. Among the different battery components, the separator allows the control of lithium ion diffusion between the electrodes. To overcome some drawbacks of liquid electrolytes, including safety and environmental issues, solid polymer electrolytes (SPEs) are being developed. In this work, a UV photocurable polyurethane acrylate (PUA) resin has been blended with lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) up to 30 wt% LiTFSI content to reach a maximum ionic conductivity of 0.0032 mS/cm at room temperature and 0.09 mS/cm at 100 ℃. Those values allowed applying the developed materials as photocurable SPE in Swagelok type Li/C-LiFePO_(4) half-cells, reaching a battery discharge capacity value of 139 mAh.g^(−1) at C/30 rate. Those results, together with the theoretical studies of the discharge capacity at different C-rates and temperatures for batteries with LiTFSI/PUA SPE demonstrate the suitability of the developed photocurable SPE for LIB applications.

关键词： Solid polymer electrolytes Photocuring Polyurethane acrylate LiTFSI Li-ion batteries

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Tamoxifen:an FdA approved drug with neuroprotective effects for spinal cord injury recovery

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Neural Regeneration Research 2016年第8期11卷 1208-1211页

作者： Jennifer M.Colón Jorge d.miranda department of Physiology School of MedicineUniversity of Puerto Rico Medical Sciences Campus

Spinal cord injury（SCI） is a condition without a cure,affecting sensory and/or motor *** physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal *** these complex set of events are damage of the blood-brain barrier,edema formation,inflammation,oxidative stress,demyelination,reactive gliosis and *** multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival,regeneration,vascular reorganization and synaptic ***,a selective estrogen receptor modulator,is an FdA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating *** investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after *** suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant,anti-inflammatory and anti-gliotic responses.A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this *** addition,the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be *** review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

关键词： selective estrogen receptor modulator trauma antioxidant anti-inflammatory regeneration reactive gliosis demyelination, estradiol

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Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury

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Neural Regeneration Research 2015年第3期10卷 385-390页

作者： Iris K.Salgado Aranza I.Torrado Jose M.Santiago Jorge d.miranda department of Physiology School of MedicineUniversity of Puerto Rico Medical Sciences Campus University of Puerto Rico Carolina Campus Department of Natural Sciences

Spinal cord injury （SCI） is a devastating condition that produces significant changes in the life- style of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI： an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents （tamoxifen and a Src kinase family inhibitor known as PP2） that have been shown in our laboratory to produce neuroprotective （increase cell survival） and/or regenerative （axonal outgrowth） actions. The animal model used in our laboratory is adult female rat （N250 g） with a moderate contusion （12.5 mm） to the spinal cord at the T10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet （Innovative Research of America, Sarasota, FL, USA） or by intraperitoneal injections （1.5 mg/kg, every 3 days）, respectively, to produce a long-term effect （28 days）. Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regen- erative activity in vertebrates with SCI.

关键词： tamoxifen Src kinase PP2 trauma regeneration neuroprotection

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Long-term treatment with PP2 after spinal cord injury resulted in functional locomotor recovery and increased spared tissue

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Neural Regeneration Research 2014年第24期9卷 2164-2173页

作者： Odrick R.Rosas Aranza I.Torrado Jose M.Santiago Ana E.Rodriguez Iris K.Salgado Jorge d.miranda department of Physiology School of Medicine University of Puerto Rico Medical Sciences Campus department of Natural Sciences University of Puerto Rico Carolina Campus

The spinal cord has the ability to regenerate but the microenvironment generated after trauma reduces that capacity. An increase in Src family kinase （SFK） activity has been implicated in neuropathological conditions associated with central nervous system trauma. Therefore, we hypothesized that a decrease in SFK activation by a long-term treatment with 4-amino-5-（4- chlorophenyl）-7-（t-butyl）pyrazolo[3,4-d]pyramidine （PP2）, a selective SFK inhibitor, after spinal cord contusion with the New York University （NYU） impactor device would generate a permissive environment that improves axonal sprouting and/or behavioral activity. Results demonstrated that long-term blockade of SFK activation with PP2 increases locomotor activity at 7, 14, 21 and 28 days post-iniury in the Basso, Beattie, and Bresnahan open field test, round and square beam crossing tests. In addition, an increase in white matter spared tissue and serotonin fiber density was observed in animals treated with PP2. However, blockade of SFK activity did not change the astrocytic response or infiltration of cells from the immune system at 28 days post-injury. Moreover, a reduced SFK activity with PP2 diminished Ephexin （a guanine nudeotide exchange factor） phosphorylation in the acute phase （4 days post-injury） after trauma. Together, these findings suggest a potential role of SFK in the regulation of spared tissue and/or axonal outgrowth that may result in functional locomotor recovery during the pathophysiology generated after spinal cord injury. Our study also points out that ephexinl phosphorylation （activation） by SFK action may be involved in the repulsive microenvironment generated after spinal cord injury.

关键词： nerve regeneration trauma regeneration Src family kinase Eph receptors ephexin spared tissue locomotor recovery GFAP Ed1 serotonin fibers neural regeneration

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3 T MR扩散加权成像描述前列腺癌的最佳b值是什么?

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国际医学放射学杂志 2012年第3期 296-297页

作者： T.Metens d.miranda J.Absil C.Matos 范璐 Resonance Magnetique Hpital ErasmeUniversité Libre de Bruxelles808 Route de Lennik1070 BruxellesBelgiqueBelgium

目的确定3TMR扩散加权成像显示前列腺癌的最佳b值。方法41例经活检证实前列腺癌的病人用16通道线圈采用5个b值(0、1000、1500、2000、2500s/mm2)的3TMR扩散加权成像检查。对比不同b值影像的最佳病灶显

关键词：前列腺癌 MRI 扩散高b值高场MRI

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Therapies for Tau-associated neurodegenerative disorders:targeting molecules,synapses,and cells

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Neural Regeneration Research 2023年第12期18卷 2633-2637页

作者： miranda Robbins MRC Laboratory of Molecular Biology Cambridge Biomedical CampusFrancis Crick AveTrumpingtonCambridgeUKUniversity of CambridgeDepartment of ZoologyCambridgeUK

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and N-methyl-d-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.

关键词： Alzheimer's disease antibody frontotemporal dementia immunotherapy small molecules synapses tau therapeutics

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Tracking Power System State Evolution with Maximum-correntropy-based Extended Kalman Filter

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Journal of Modern Power Systems and Clean Energy 2020年第4期8卷 616-626页

作者： Julio A.d.Massignan João B.A.London Jr. Vladimiro miranda IEEE department of Electrical and Computing Engineering School of Engineering of São CarlosUniversity of São PauloSão CarlosBrazil Faculty of Engineering University of Porto and INESC TECPortoPortugal

This paper develops a novel approach to track power system state evolution based on the maximum correntropy criterion,due to its robustness against non-Gaussian *** includes the temporal aspects on the estimation process within a maximum-correntropy-based extended Kalman filter(MCEKF),which is able to deal with both nonlinear supervisory control and data acquisition(SCAdA)and phasor measurement unit(PMU)measurement *** representing the behavior of the state variables with a nonparametric model within the kernel density estimation,it is possible to include abrupt state transitions as part of the process noise with non-Gaussian ***,a novel strategy to update the size of Parzen windows in the kernel estimation is proposed to suppress the effects of suspect *** properly adjusting the kernel bandwidth,the proposed MCEKF keeps its accuracy during sudden load changes and contingencies,or in the presence of bad *** with IEEE test systems and the Brazilian interconnected system are carried *** results show that the method deals with non-Gaussian noises in both the process and measurement,and provides accurate estimates of the system state under normal and abnormal conditions.

关键词： Tracking state estimation Kalman filter maximum correntropy power system Parzen window

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On Building Practical Biocomputers for Real-world Applications： Receptacles for Culturing Slime Mould Memristors and Component Standardisation

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Journal of Bionic Engineering 2017年第1期14卷 151-162页

作者： Edward Braund Eduardo Reck miranda Interdisciplinary Centre for Computer Music Research (ICCMR) The House Plymouth University Drake Circus UK PL4 8AA

Our application of bionic engineering is novel： we are interested in developing hybrid hardware-wetware systems for music. This paper introduces receptacles for culturing Physarum polycephalum-based memristors that are highly accessible to the creative practitioner. The myxomycete Physarum polycephalum is an amorphous unicellular organism that has been found to exhibit memristive properties. Such a discovery has potential to allow us to move towards engineering electrical systems that encompass Physarum polycephalum components. To realise this potential, it is necessary to address some of the constraints associated with harnessing living biological entities in systems for real-time application. Within the paper, we present 3d printed receptacles designed to standardise both the production of components and memristive observations. Subsequent testing showed a significant decrease in growth time, increased lifespan, and superior similarity in component-to-component responses. The results indicate that our receptacle design may provide means of implementing hybrid electrical systems for music technology.

关键词： unconventional computing Physarum polycephalum computer music biological computing memristor

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development of a 3d model for particle-wall collision and induced rotation and its influence on particle trajectories

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Particuology 2024年第11期94卷 211-228页

作者： Cairen miranda John Palmore Jr. department of Mechanical Engineering Virginia TechBlacksburg24060VAUSA department of Mechanical Engineering University of WashingtonSeattle98195WAUSA

The present research focuses on improving the prediction of rotating particle *** particle-surface collision models do not accurately predict the particle rebound when taking rotation into *** data,such as the studies by Gorham and Kharaz(2000),Buck,Tang,Heinrich,deen and Kuipers(2017),and dong and Moys(2006)show that the Tsuji,Oshima and Morikawa(1985)model is inaccurate due to the incorrect tangential coefficient of restitution ***,Kuipers,Mohd Salleh,Stein,and Seville(2001)introduced a similar model to the work by Tsuji et al.(1985)which includes a tangential coefficient of restitution but is only in two dimensions and does not consider out of plane *** work re-derives the particle collision model from the impulse equations for binary collisions in 3d while considering rotating *** derived equations in this work compares well to experimental particle-surface impact *** implications of this model are seen by investigating erosion due to particle collision in a simple pipe *** is shown that Tsuji et al.(1985)over predicts the *** small differences in particle trajectories between the present model and the Tsuji et al.(1985)model will grow in complex flows with multiple close range particle impacts leading to inaccurate erosion predictions which will negatively impact the design of turbomachinery and pneumatic pipes.

关键词： Particle collisions CFd Rotation Three dimensional

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