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1.
J Neurosci ; 44(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37963762

RESUMO

Spasticity is a hyperexcitability disorder that adversely impacts functional recovery and rehabilitative efforts after spinal cord injury (SCI). The loss of evoked rate-dependent depression (RDD) of the monosynaptic H-reflex is indicative of hyperreflexia, a physiological sign of spasticity. Given the intimate relationship between astrocytes and neurons, that is, the tripartite synapse, we hypothesized that astrocytes might have a significant role in post-injury hyperreflexia and plasticity of neighboring neuronal synaptic dendritic spines. Here, we investigated the effect of selective Rac1KO in astrocytes (i.e., adult male and female mice, transgenic cre-flox system) on SCI-induced spasticity. Three weeks after a mild contusion SCI, control Rac1wt animals displayed a loss of H-reflex RDD, that is, hyperreflexia. In contrast, transgenic animals with astrocytic Rac1KO demonstrated near-normal H-reflex RDD similar to pre-injury levels. Reduced hyperreflexia in astrocytic Rac1KO animals was accompanied by a loss of thin-shaped dendritic spine density on α-motor neurons in the ventral horn. In SCI-Rac1wt animals, as expected, we observed the development of dendritic spine dysgenesis on α-motor neurons associated with spasticity. As compared with WT animals, SCI animals with astrocytic Rac1KO expressed increased levels of the glial-specific glutamate transporter, glutamate transporter-1 in the ventral spinal cord, potentially enhancing glutamate clearance from the synaptic cleft and reducing hyperreflexia in astrocytic Rac1KO animals. Taken together, our findings show for the first time that Rac1 activity in astrocytes can contribute to hyperreflexia underlying spasticity following SCI. These results reveal an opportunity to target cell-specific molecular regulators of H-reflex excitability to manage spasticity after SCI.Significance Statement Spinal cord injury leads to stretch reflex hyperexcitability, which underlies the clinical symptom of spasticity. This study shows for the first time that astrocytic Rac1 contributes to the development of hyperreflexia after SCI. Specifically, astrocytic Rac1KO reduced SCI-related H-reflex hyperexcitability, decreased dendritic spine dysgenesis on α-motor neurons, and elevated the expression of the astrocytic glutamate transporter-1 (GLT-1). Overall, this study supports a distinct role for astrocytic Rac1 signaling within the spinal reflex circuit and the development of SCI-related spasticity.


Assuntos
Reflexo Anormal , Traumatismos da Medula Espinal , Camundongos , Masculino , Feminino , Animais , Astrócitos/metabolismo , Neurônios Motores/fisiologia , Medula Espinal/metabolismo , Animais Geneticamente Modificados , Reflexo H , Sistema X-AG de Transporte de Aminoácidos/metabolismo
2.
J Physiol ; 602(19): 5061-5081, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39231098

RESUMO

Hyperreflexia associated with spasticity is a prevalent neurological condition characterized by excessive and exaggerated reflex responses to stimuli. Hyperreflexia can be caused by several diseases including multiple sclerosis, stroke and spinal cord injury (SCI). Although we have previously identified the contribution of the RAC1-PAK1 pathway underlying spinal hyperreflexia with SCI-induced spasticity, a feasible druggable target has not been validated. To assess the utility of targeting PAK1 to attenuate H-reflex hyperexcitability, we administered Romidepsin, a clinically available PAK1 inhibitor, in Thy1-YFP reporter mice. We performed longitudinal EMG studies with a study design that allowed us to assess pathological H-reflex changes and drug intervention effects over time, before and after contusive SCI. As expected, our results show a significant loss of rate-dependent depression - an indication of hyperreflexia and spasticity - 1 month following SCI as compared with baseline, uninjured controls (or before injury). Romidepsin treatment reduced signs of hyperreflexia in comparison with control cohorts and in pre- and post-drug intervention in SCI animals. Neuroanatomical study further confirmed drug response, as romidepsin treatment also reduced the presence of SCI-induced dendritic spine dysgenesis on α-motor neurons. Taken together, our findings extend previous work demonstrating the utility of targeting PAK1 activity in SCI-induced spasticity and support the novel use of romidepsin as an effective tool for managing spasticity. KEY POINTS: PAK1 plays a role in contributing to the development of spinal cord injury (SCI)-induced spasticity by contributing to dendritic spine dysgenesis. In this study, we explored the preclinical utility of inhibiting PAK1 to reduce spasticity and dendritic spine dysgenesis in an SCI mouse model. Romidepsin is a PAK1 inhibitor approved in the US in 2009 for the treatment of cutaneous T-cell lymphoma. Here we show that romidepsin treatment after SCI reduced SCI-induced H-reflex hyperexcitability and abnormal α-motor neuron spine morphology. This study provides compelling evidence that romidepsin may be a promising therapeutic approach for attenuating SCI-induced spasticity.


Assuntos
Depsipeptídeos , Reflexo H , Traumatismos da Medula Espinal , Quinases Ativadas por p21 , Animais , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Quinases Ativadas por p21/antagonistas & inibidores , Quinases Ativadas por p21/metabolismo , Depsipeptídeos/farmacologia , Camundongos , Reflexo H/efeitos dos fármacos , Feminino , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Camundongos Endogâmicos C57BL , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/fisiologia , Masculino
3.
J Neurophysiol ; 130(5): 1358-1366, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37877184

RESUMO

Spasticity is a chronic neurological complication associated with spinal cord injury (SCI), characterized by increased muscle tone and stiffness. A physiological sign of spasticity is hyperreflexia, evident by the loss of evoked rate-dependent depression (RDD) in the H-reflex. Although previous work has shown that SCI-induced astrogliosis contributes to hyperexcitability disorders, including neuropathic pain and spasticity, it is unclear how reactive astrocytes can modulate synaptic transmission within the injured spinal cord. To study astrocytes' role in post-SCI hyperreflexia, we examined glutamate transporter-1 (GLT-1) and postsynaptic density protein 95 (PSD-95) proteins in astrocytes and neurons, respectively, within the ventral horn (lamina IX) below the level of injury (spinal segment L4-5). The close juxtaposition of GLT-1 and PSD-95 markers is a molecular correlate of tripartite synapses and is thought to be a key element in the astrocyte-induced plasticity of neuronal synapses. Our study compared animals with and without SCI-induced hyperreflexia and spasticity and investigated potential synaptic abnormalities associated with astrocyte involvement. As expected, 4 wk after SCI, we observed a loss in evoked H-reflex RDD in hindlimb electromyogram recordings, i.e., hyperreflexia, in contrast to uninjured sham. Importantly, our main findings show a significant increase in the presence of GLT-1-PSD-95 tripartite synapses in the ventral spinal cord motor regions of animals exhibiting SCI-induced hyperreflexia. Taken together, our study suggests the involvement of astrocyte-neuron synaptic complexes in the plasticity-driven progression of chronic spasticity.NEW & NOTEWORTHY The role of astrocytes in H-reflex hyperexcitability following SCI remains understudied. Our findings establish a relationship between GLT-1 expression, its proximity to neuronal PSD-95 in the spinal cord ventral horn, and the loss of H-reflex RDD, i.e., hyperreflexia. Our findings provide a new perspective on synaptic alterations and the development of SCI-related spasticity.


Assuntos
Astrócitos , Traumatismos da Medula Espinal , Animais , Astrócitos/metabolismo , Reflexo Anormal , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Neurônios Motores/fisiologia , Sinapses/metabolismo
4.
Phys Rev Lett ; 129(1): 016401, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35841573

RESUMO

Valence transition could induce structural, insulator-metal, nonmagnetic-magnetic and superconducting transitions in rare-earth metals and compounds, while the underlying physics remains unclear due to the complex interaction of localized 4f electrons as well as their coupling with itinerant electrons. The valence transition in the elemental metal europium (Eu) still has remained as a matter of debate. Using resonant x-ray emission scattering and x-ray diffraction, we pressurize the states of 4f electrons in Eu and study its valence and structure transitions up to 160 GPa. We provide compelling evidence for a valence transition around 80 GPa, which coincides with a structural transition from a monoclinic (C2/c) to an orthorhombic phase (Pnma). We show that the valence transition occurs when the pressure-dependent energy gap between 4f and 5d electrons approaches the Coulomb interaction. Our discovery is critical for understanding the electrodynamics of Eu, including magnetism and high-pressure superconductivity.

5.
J Neurosci ; 40(22): 4297-4308, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32371602

RESUMO

Neuropathic pain is an intractable medical condition with few or no options for effective treatment. Emerging evidence shows a strong structure-function relationship between dendritic spine dysgenesis and the presence of neuropathic pain. Postmortem tissue analyses can only imply dynamic structural changes associated with injury-induced pain. Here, we profiled the in vivo dynamics of dendritic spines over time on the same superficial dorsal horn (lamina II) neurons before and after peripheral nerve injury-induced pain. We used a two-photon, whole-animal imaging paradigm that permitted repeat imaging of the same dendritic branches of these neurons in C57/Bl6 Thy1-YFP male mice. Our study demonstrates, for the first time, the ongoing, steady-state changes in dendritic spine dynamics in the dorsal horn associated with peripheral nerve injury and pain. Ultimately, the relationship between altered dendritic spine dynamics and neuropathic pain may serve as a structure-based opportunity to investigate mechanisms of pain following injury and disease.SIGNIFICANCE STATEMENT This work is important because it demonstrates for the first time: (1) the powerful utility of intravital study of dendritic spine dynamics in the superficial dorsal horn; (2) that nerve injury-induced pain triggers changes in dendritic spine steady-state behavior in the spinal cord dorsal horn; and (3) this work opens the door to further investigations in vivo of spinal cord dendritic spine dynamics in the context of injury and disease.


Assuntos
Espinhas Dendríticas/patologia , Traumatismos dos Nervos Periféricos/patologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica , Traumatismos dos Nervos Periféricos/fisiopatologia , Corno Dorsal da Medula Espinal/patologia , Corno Dorsal da Medula Espinal/fisiopatologia
6.
Inorg Chem ; 60(13): 9320-9331, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34152127

RESUMO

Analogous to 2D layered transition-metal dichalcogenides, the TlSe family of quasi-one dimensional chain materials with the Zintl-type structure exhibits novel phenomena under high pressure. In the present work, we have systematically investigated the high-pressure behavior of TlInTe2 using Raman spectroscopy, synchrotron X-ray diffraction (XRD), and transport measurements, in combination with first principles crystal structure prediction (CSP) based on evolutionary approach. We found that TlInTe2 undergoes a pressure-induced semiconductor-to-semimetal transition at 4 GPa, followed by a superconducting transition at 5.7 GPa (with Tc = 3.8 K). An unusual giant phonon mode (Ag) softening appears at ∼10-12 GPa as a result of the interaction of optical phonons with the conduction electrons. The high-pressure XRD and Raman spectroscopy studies reveal that there is no structural phase transitions observed up to the maximum pressure achieved (33.5 GPa), which is in agreement with our CSP calculations. In addition, our calculations predict two high-pressure phases above 35 GPa following the phase transition sequence as I4/mcm (B37) → Pbcm → Pm3̅m (B2). Electronic structure calculations suggest Lifshitz (L1 & L2-type) transitions near the superconducting transition pressure. Our findings on TlInTe2 open up a new avenue to study unexplored high-pressure novel phenomena in TlSe family induced by Lifshitz transition (electronic driven), giant phonon softening, and electron-phonon coupling.

7.
Brain ; 143(8): 2421-2436, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32830219

RESUMO

Vincristine, a widely used chemotherapeutic agent, produces painful peripheral neuropathy. The underlying mechanisms are not well understood. In this study, we investigated whether voltage-gated sodium channels are involved in the development of vincristine-induced neuropathy. We established a mouse model in which repeated systemic vincristine treatment results in the development of significant mechanical allodynia. Histological examinations did not reveal major structural changes at proximal sciatic nerve branches or distal toe nerve fascicles at the vincristine dose used in this study. Immunohistochemical studies and in vivo two-photon imaging confirmed that there is no significant change in density or morphology of intra-epidermal nerve terminals throughout the course of vincristine treatment. These observations suggest that nerve degeneration is not a prerequisite of vincristine-induced mechanical allodynia in this model. We also provided the first detailed characterization of tetrodotoxin-sensitive (TTX-S) and resistant (TTX-R) sodium currents in dorsal root ganglion neurons following vincristine treatment. Accompanying the behavioural hyperalgesia phenotype, voltage-clamp recordings of small and medium dorsal root ganglion neurons from vincristine-treated animals revealed a significant upregulation of TTX-S Na+ current in medium but not small neurons. The increase in TTX-S Na+ current density is likely mediated by Nav1.6, because in the absence of Nav1.6 channels, vincristine failed to alter TTX-S Na+ current density in medium dorsal root ganglion neurons and, importantly, mechanical allodynia was significantly attenuated in conditional Nav1.6 knockout mice. Our data show that TTX-S sodium channel Nav1.6 is involved in the functional changes of dorsal root ganglion neurons following vincristine treatment and it contributes to the maintenance of vincristine-induced mechanical allodynia.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.6/metabolismo , Células Receptoras Sensoriais/metabolismo , Vincristina/toxicidade , Animais , Feminino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos
8.
Proc Natl Acad Sci U S A ; 115(8): 1742-1747, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29432162

RESUMO

Knowledge of the structure and properties of silicate magma under extreme pressure plays an important role in understanding the nature and evolution of Earth's deep interior. Here we report the structure of MgSiO3 glass, considered an analog of silicate melts, up to 111 GPa. The first (r1) and second (r2) neighbor distances in the pair distribution function change rapidly, with r1 increasing and r2 decreasing with pressure. At 53-62 GPa, the observed r1 and r2 distances are similar to the Si-O and Si-Si distances, respectively, of crystalline MgSiO3 akimotoite with edge-sharing SiO6 structural motifs. Above 62 GPa, r1 decreases, and r2 remains constant, with increasing pressure until 88 GPa. Above this pressure, r1 remains more or less constant, and r2 begins decreasing again. These observations suggest an ultrahigh-pressure structural change around 88 GPa. The structure above 88 GPa is interpreted as having the closest edge-shared SiO6 structural motifs similar to those of the crystalline postperovskite, with densely packed oxygen atoms. The pressure of the structural change is broadly consistent with or slightly lower than that of the bridgmanite-to-postperovskite transition in crystalline MgSiO3 These results suggest that a structural change may occur in MgSiO3 melt under pressure conditions corresponding to the deep lower mantle.

9.
Phys Rev Lett ; 125(20): 205701, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33258638

RESUMO

Pair distribution function measurement of SiO_{2} glass up to 120 GPa reveals changes in the first-, second-, and third-neighbor distances associated with an increase in Si coordination number C_{Si} to >6 above 95 GPa. Packing fractions of Si and O determined from the first- and second-neighbor distances show marked changes accompanied with the structural evolution from C_{Si}=6 to >6. Structural constraints in terms of ionic radius ratio of Si and O, and ratio of nonbonded radius to bonded Si─O distance support the structural evolution of SiO_{2} glass with C_{Si}>6 at high pressures.

10.
J Chem Phys ; 150(24): 244201, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31255054

RESUMO

Amorphous-amorphous transformations in H2O have been studied under rapid isothermal compression and decompression in a diamond anvil cell together with in situ x-ray diffraction measurements using brilliant synchrotron radiation. The experimental pathways provide a density-driven approach for studying polyamorphic relations among low-, high-, and very high-density amorphs (LDA, HDA, VHDA) in a pressure range of 0-3.5 GPa at temperatures of 145-160 K. Our approach using rapid (de)compression allows for studying the polyamorphic transformations at higher temperatures than the conditions previously studied under slow (de)compression or isobaric annealing. Multiple compression-decompression cycles can be integrated with in situ x-ray measurements, thus facilitating the study of repeatability and reversibility of the polyamorphic transformations. Fast in situ x-ray diffraction measurements allow for obtaining detailed insight into the structural changes across polyamorphic transformations regarding the (dis)continuity, reversibility, and possible intermediate forms. As demonstrated at isothermal conditions of 145 K and 155 K, the polyamorphic transformations are characterized by a sharp and reversible LDA-VHDA transformation, with an HDA-like form (referred to as HDA') appearing as an intermediate state. The LDA-VHDA transformation is found to occur in two steps: a discontinuous transition between LDA and HDA' and a continuous change within HDA' involving structural reconfigurations and finally converging to VHDA.

11.
Proc Natl Acad Sci U S A ; 113(13): 3436-41, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26976585

RESUMO

Knowledge of pressure-induced structural changes in glasses is important in various scientific fields as well as in engineering and industry. However, polyamorphism in glasses under high pressure remains poorly understood because of experimental challenges. Here we report new experimental findings of ultrahigh-pressure polyamorphism in GeO2 glass, investigated using a newly developed double-stage large-volume cell. The Ge-O coordination number (CN) is found to remain constant at ∼6 between 22.6 and 37.9 GPa. At higher pressures, CN begins to increase rapidly and reaches 7.4 at 91.7 GPa. This transformation begins when the oxygen-packing fraction in GeO2 glass is close to the maximal dense-packing state (the Kepler conjecture = ∼0.74), which provides new insights into structural changes in network-forming glasses and liquids with CN higher than 6 at ultrahigh-pressure conditions.

12.
Proc Natl Acad Sci U S A ; 113(7): 1714-8, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26831105

RESUMO

Metallic glass (MG) is an important new category of materials, but very few rigorous laws are currently known for defining its "disordered" structure. Recently we found that under compression, the volume (V) of an MG changes precisely to the 2.5 power of its principal diffraction peak position (1/q1). In the present study, we find that this 2.5 power law holds even through the first-order polyamorphic transition of a Ce68Al10Cu20Co2 MG. This transition is, in effect, the equivalent of a continuous "composition" change of 4f-localized "big Ce" to 4f-itinerant "small Ce," indicating the 2.5 power law is general for tuning with composition. The exactness and universality imply that the 2.5 power law may be a general rule defining the structure of MGs.

13.
Mol Pain ; 14: 1744806918788648, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29956587

RESUMO

Painful burn injuries are among the most debilitating form of trauma, globally ranking in the top 15 leading causes of chronic disease burden. Despite its prevalence, however, chronic pain after burn injury is under-studied. We previously demonstrated the contribution of the Rac1-signaling pathway in several models of neuropathic pain, including burn injury. However, Rac1 belongs to a class of GTPases with low therapeutic utility due to their complex intracellular dynamics. To further understand the mechanistic underpinnings of burn-induced neuropathic pain, we performed a longitudinal study to address the hypothesis that inhibition of the downstream effector of Rac1, Pak1, will improve pain outcome following a second-degree burn injury. Substantial evidence has identified Pak1 as promising a clinical target in cognitive dysfunction and is required for dendritic spine dysgenesis associated with many neurological diseases. In our burn injury model, mice exhibited significant tactile allodynia and heat hyperalgesia and dendritic spine dysgenesis in the dorsal horn. Activity-dependent expression of c-fos also increased in dorsal horn neurons, an indicator of elevated central nociceptive activity. To inhibit Pak1, we repurposed an FDA-approved inhibitor, romidepsin. Treatment with romidepsin decreased dendritic spine dysgenesis, reduced c-fos expression, and rescued pain thresholds. Drug discontinuation resulted in a relapse of cellular correlates of pain and in lower pain thresholds in behavioral tests. Taken together, our findings identify Pak1 signaling as a potential molecular target for therapeutic intervention in traumatic burn-induced neuropathic pain.


Assuntos
Queimaduras/complicações , Espinhas Dendríticas/patologia , Neuralgia/etiologia , Neuralgia/metabolismo , Pele/inervação , Quinases Ativadas por p21/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Depsipeptídeos/uso terapêutico , Modelos Animais de Doenças , Feminino , Estudos Longitudinais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Medula Espinal/patologia , Proteínas rac1 de Ligação ao GTP/metabolismo
14.
Phys Rev Lett ; 119(13): 135701, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-29341714

RESUMO

We report the results of in situ structural characterization of the amorphization of crystalline ice Ih under compression and the relaxation of high-density amorphous (HDA) ice under decompression at temperatures between 96 and 160 K by synchrotron x-ray diffraction. The results show that ice Ih transforms to an intermediate crystalline phase at 100 K prior to complete amorphization, which is supported by molecular dynamics calculations. The phase transition pathways show clear temperature dependence: direct amorphization without an intermediate phase is observed at 133 K, while at 145 K a direct Ih-to-IX transformation is observed; decompression of HDA shows a transition to low-density amorphous ice at 96 K and ∼1 Pa, to ice Ic at 135 K and to ice IX at 145 K. These observations show that the amorphization of compressed ice Ih and the recrystallization of decompressed HDA are strongly dependent on temperature and controlled by kinetic barriers. Pressure-induced amorphous ice is an intermediate state in the phase transition from the connected H-bond water network in low pressure ices to the independent and interpenetrating H-bond network of high-pressure ices.

15.
Chemphyschem ; 18(23): 3315-3319, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-28910522

RESUMO

The thermoelectric properties of polycrystalline SnTe have been measured up to 4.5 GPa at 330 K. SnTe shows an enormous enhancement in Seebeck coefficient, greater than 200 % after 3 GPa, which correlates to a known pressure-induced structural phase transition that is observed through simultaneous in situ X-ray diffraction measurement. Electrical resistance and relative changes to the thermal conductivity were also measured, enabling the determination of relative changes in the dimensionless figure of merit (ZT), which increases dramatically after 3 GPa, reaching 350 % of the lowest pressure ZT value. The results demonstrate a fundamental relationship between structure and thermoelectric behaviours and suggest that pressure is an effective tool to control them.

16.
J Synchrotron Radiat ; 23(Pt 6): 1368-1378, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27787242

RESUMO

A new sample cell assembly design for the Paris-Edinburgh type large-volume press for simultaneous measurements of X-ray diffraction, electrical resistance, Seebeck coefficient and relative changes in the thermal conductance at high pressures has been developed. The feasibility of performing in situ measurements of the Seebeck coefficient and thermal measurements is demonstrated by observing well known solid-solid phase transitions of bismuth (Bi) up to 3 GPa and 450 K. A reversible polarity flip has been observed in the Seebeck coefficient across the Bi-I to Bi-II phase boundary. Also, successful Seebeck coefficient measurements have been performed for the classical high-temperature thermoelectric material PbTe under high pressure and temperature conditions. In addition, the relative change in the thermal conductivity was measured and a relative change in ZT, the dimensionless figure of merit, is described. This new capability enables pressure-induced structural changes to be directly correlated to electrical and thermal properties.

17.
Mult Scler ; 21(12): 1485-95, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26286700

RESUMO

BACKGROUND: Anti-oxidant compounds that are found in over-the-counter (OTC) supplements and foods are gaining interest as treatments for multiple sclerosis (MS). They are widely used by patients, sometimes without a clear evidence base. OBJECTIVE: We conducted a systematic review of animal and clinical research to determine the evidence for the benefits of OTC anti-oxidants in MS. METHODS: Using predefined criteria, we searched key databases. Two authors scrutinized all studies against inclusion/exclusion criteria, assessed study risk-of-bias and extracted results. RESULTS: Of the 3507 titles, 145 met criteria and included compounds, α(alpha)-lipoic acid (ALA), anti-oxidant vitamins, Ginkgo biloba, quercetin, resveratrol and epigallocatechin-3-gallate (ECGC). The strongest evidence to support OTC anti-oxidants was for compounds EGCG and ALA in animal models; both consistently showed anti-inflammatory/anti-oxidant effects and reduced neurological impairment. Only vitamin E, Ginkgo biloba and ALA were examined for efficacy in pilot clinical trials with either conflicting evidence or evidence of no benefit. CONCLUSION: OTC anti-oxidants EGCG and ALA show the most consistent benefit, however only in preclinical studies. There is no evidence that they alter MS relapses or progression. Future work should focus on testing more of these therapies for clinical efficacy before recommending them to MS patients.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Ginkgo biloba , Esclerose Múltipla/tratamento farmacológico , Medicamentos sem Prescrição/farmacologia , Quercetina/farmacologia , Estilbenos/farmacologia , Ácido Tióctico/farmacologia , Animais , Catequina/farmacologia , Humanos , Resveratrol
18.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38980129

RESUMO

The diamond anvil cell (DAC) has been widely used in high-pressure research. Despite significant progress over the past five decades, the opposed anvil geometry in the DAC inevitably leads to a disk-shaped sample configuration at high pressure. This intrinsic limitation is largely responsible for the large pressure and temperature gradients in the DAC, which often compromise precise experiments and their characterizations. We designed and fabricated a multi-axis diamond anvil cell (MDAC) by adopting the concept of a multi-anvil apparatus but using single crystal diamonds as the anvil material. Preliminary data show that the MDAC can generate extreme pressure conditions above 100 GPa. The advantages of the MDAC over a traditional opposed anvil DAC include thicker, voluminous samples, quasi-hydrostatic, or designed deviatoric stress conditions, and multidirectional access windows for optical applications and x-ray probes. In this article, we present the design and performance of a prototype MDAC, as well as the application prospects in high-pressure research.

19.
Phys Rev E ; 110(2-1): 024501, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39294967

RESUMO

Amber is a unique example of a fragile glass that has been extensively aged below its glass transition temperature, thus reaching a state that is not accessible under normal experimental conditions. We studied the medium-range order of Baltic amber by x-ray diffraction (XRD) at high pressures. The pressure dependences of the low-angle XRD intensity between 0 and 5 Å^{-1} were measured from 0 to 7.3 GPa by the energy-dispersive XRD. The first diffraction peak at 1.1 Å^{-1} and ambient pressure has a doublet structure consisting of the first sharp diffraction peak (FSDP) at 1.05 Å^{-1} and the second feature at 1.40 Å^{-1}. The peak position and the width of the FSDP increase as the pressure increases, while the intensity of the FSDP decreases. Below P_{0}=2.4 GPa, the rapid increase of the FSDP peak position was observed, while above P_{0}, the gradual increase was observed. Below P_{0}, voids and holes in a relatively low-density state are suppressed, whereas above P_{0}, the suppression becomes mild. Such a change suggests the crossover from the low- to high-density state at P_{0}. There is a close correlation between the pressure dependence of XRD and previously reported sound velocity results. The correlation between the mean-square fluctuation of the shear modulus on the nanometer scale and fragility in amber and other glass formers is also discussed.

20.
Sci Adv ; 10(36): eado8550, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39241074

RESUMO

The eruption of deeply sourced kimberlite magma offers the fastest route to bring deep-seated volatiles back to the Earth's surface. However, the viscosity of kimberlite magma, a factor governing its migration and eruption dynamics within Earth, remains poorly constrained. We conducted synchrotron in situ falling sphere viscometry experiments to examine kimberlite magma with different volatile contents (0 to 5 wt % H2O and 2 to 8 wt % CO2) under high pressure-temperature conditions. The results reveal that the viscosity of volatile-rich kimberlite magma is ~1 to 2 orders lower than that of mid-ocean ridge basalt (MORB) and comparable to the ultramobile pure carbonate melt. Using the measured viscosity values, we simulated the ascent and eruption process of kimberlite magma. We found that a minimum content of ~0.5 wt % water in the primitive magma is necessary to allow the ultrafast eruption process of kimberlite, thereby enabling the preservation of diamonds and high-pressure mineral inclusions transported by the magma.

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