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1.
Nat Immunol ; 20(2): 152-162, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30643259

RESUMO

Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER-Golgi intermediate compartment. Here, we found that deficiency in the Ca2+ sensor stromal interaction molecule 1 (STIM1) caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient with combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and coexpression of full-length STIM1 or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1-STING circuit that maintains the resting state of the STING pathway.


Assuntos
Interferon Tipo I/imunologia , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Animais , Pré-Escolar , Chlorocebus aethiops , DNA Viral/imunologia , Modelos Animais de Doenças , Retículo Endoplasmático/metabolismo , Fibroblastos , Técnicas de Inativação de Genes , Células HEK293 , Herpes Simples/imunologia , Herpes Simples/virologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Humanos , Imunidade Inata , Células Jurkat , Macrófagos , Masculino , Proteínas de Membrana/imunologia , Camundongos , Camundongos Knockout , Células NIH 3T3 , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/imunologia , Cultura Primária de Células , Imunodeficiência Combinada Severa/sangue , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/imunologia , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/imunologia , Células Vero
2.
Euro Surveill ; 27(2)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35027105

RESUMO

The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong's COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group's (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group's (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Antivirais , Doadores de Sangue , Hong Kong , Humanos , RNA Mensageiro , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados , Vacinas Sintéticas , Vacinas de mRNA
3.
Vox Sang ; 116(5): 504-512, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33196117

RESUMO

BACKGROUND AND OBJECTIVES: Blood safety hinges not just on the scientific rationale for deferral period but potential donors' compliance with the prevailing policy. This study aimed to investigate donors' awareness, attitudes and compliance with the two-phased policy implementation of time-limited deferral for men who have sex with men (MSM) in Hong Kong. MATERIALS AND METHODS: Three rounds of questionnaire survey were conducted between July 2017 and June 2019 covering the periods of pre-implementation (Round A), post-implementation without and with pre-donation questionnaire revision (Round B and C). Chi-square test and multivariable regression analysis were performed. RESULTS: Of 3085 donors recruited, 968, 1036 and 1081 completed the surveys in Round A, B and C, respectively. The non-compliance rate of MSM remained stable at 0·6% (3/497), 0·4% (2/551) and 0·5% (3/587) among male donors in Round A, B and C, respectively. Two MSM donors from Round C complying with the prevailing policy were identified. About two-thirds (60·7%) of respondents from Round B and C were unaware of the policy change. Overall, over 80% were either neutral or positive about the change. CONCLUSION: Our study showed a consistently low non-compliance rate of MSM over the three periods. The generally high level of acceptance of time-limited deferral among donors lends support to science-based policy development to protect blood safety. The identification of compliant MSM donors suggests that the 12-month deferral is effective and acceptable to MSM. With a deferral period far exceeding the window period, it is a step towards a more equitable policy.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Segurança do Sangue/estatística & dados numéricos , Homossexualidade Masculina/estatística & dados numéricos , Cooperação do Paciente , Adulto , Doadores de Sangue/psicologia , Segurança do Sangue/psicologia , Homossexualidade Masculina/psicologia , Hong Kong , Humanos , Masculino , Inquéritos e Questionários
4.
J Neuroeng Rehabil ; 18(1): 89, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039346

RESUMO

BACKGROUND: Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. METHODS: We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. RESULTS: Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. CONCLUSIONS: Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies' activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke.


Assuntos
Cerebelo/fisiopatologia , Estimulação Elétrica/métodos , Neurônios/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Eletrocorticografia , Potencial Evocado Motor/fisiologia , Masculino , Ratos , Ratos Long-Evans
5.
Nanotechnology ; 31(42): 424001, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32583811

RESUMO

We present spatially and spectrally resolved emission from nanowires with a thin radial layer of GaAs embedded in AlGaAs barriers, grown radially around taper-free GaAs cores. The GaAs layers are thin enough to show quantization, and are quantum wells. Due to their shape, they are referred to as quantum well tubes (QWTs). We have investigated three different nominal QWT thicknesses: 1.5, 2.0, and 6.0 nm. They all show average emission spectra from the QWT with an energy spread corresponding to a thickness variation of ±30%. We observe no thickness gradient along the length of the nanowires. Individual NWs show a number of peaks, corresponding to different QW thicknesses. Apart from the thinnest QWT, the integrated emission from the QWTs shows homogeneous emission intensity along the NW. The thinnest QWTs show patchy emission patterns due to the incomplete coverage of the QWT. We observe a few NWs with larger diameters. The QWTs in these NWs show spatially resolved variations across the NW. An increase in the local thickness of the QWT at the corners blocks the diffusion of carriers from facet to facet, thereby enabling us to visualise the thickness variations of the radial quantum wells.

6.
Nano Lett ; 19(6): 3821-3829, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31141386

RESUMO

We report multiwavelength single InGaAs/InP quantum well nanowire light-emitting diodes grown by metal organic chemical vapor deposition using selective area epitaxy technique and reveal the complex origins of their electroluminescence properties. We observe that the single InGaAs/InP quantum well embedded in the nanowire consists of three components with different chemical compositions, axial quantum well, ring quantum well, and radial quantum well, leading to the electroluminescence emission with multiple wavelengths. The electroluminescence measurements show a strong dependence on current injection levels as well as temperatures and these are explained by interpreting the equivalent circuits in a minimized area of the device. It is also found that the electroluminescence properties are closely related to the distinctive triangular morphology with an inclined facet of the quantum well nanowire. Our study provides important new insights for further design, growth, and fabrication of high-performance quantum well-based nanowire light sources for a wide range of future optoelectronic and photonic applications.

10.
Nano Lett ; 16(7): 4361-7, 2016 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-27253040

RESUMO

Selective-area epitaxy is highly successful in producing application-ready size-homogeneous arrays of III-V nanowires without the need to use metal catalysts. Previous works have demonstrated excellent control of nanowire properties but the growth mechanisms remain rather unclear. Herein, we report a detailed growth study revealing that fundamental growth mechanisms of pure wurtzite InP ⟨111⟩A nanowires can indeed differ significantly from the simple picture of a facet-limited selective-area growth process. A dual growth regime with and without metallic droplet is found to coexist under the same growth conditions for different diameter nanowires. Incubation times and highly nonmonotonous growth rate behaviors are revealed and explained within a dedicated kinetic model.

17.
Nanotechnology ; 26(20): 205604, 2015 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-25927420

RESUMO

Obtaining compositional homogeneity without compromising morphological or structural quality is one of the biggest challenges in growing ternary alloy compound semiconductor nanowires. Here we report growth of Au-seeded InxGa1-xAs nanowires via metal-organic vapour phase epitaxy with uniform composition, morphology and pure wurtzite (WZ) crystal phase by carefully optimizing growth temperature and V/III ratio. We find that high growth temperatures allow the InxGa1-xAs composition to be more uniform by suppressing the formation of typically observed spontaneous In-rich shells. A low V/III ratio results in the growth of pure WZ phase InxGa1-xAs nanowires with uniform composition and morphology while a high V/III ratio allows pure zinc-blende (ZB) phase to form. Ga incorporation is found to be dependent on the crystal phase favouring higher Ga concentration in ZB phase compared to the WZ phase. Tapering is also found to be more prominent in defective nanowires hence it is critical to maintain the highest crystal structure purity in order to minimize tapering and inhomogeneity. The InP capped pure WZ In0.65Ga0.35As core-shell nanowire heterostructures show 1.54 µm photoluminescence, close to the technologically important optical fibre telecommunication wavelength, which is promising for application in photodetectors and nanoscale lasers.

18.
Nano Lett ; 14(10): 5865-72, 2014 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-25244584

RESUMO

With increasing interest in nanowire-based devices, a thorough understanding of the nanowire shape is required to gain tight control of the quality of nanowire heterostructures and improve the performance of related devices. We present a systematic study of the sidewalls of Au-catalyzed GaAs nanowires by investigating the faceting process from the beginning with vapor-liquid-solid (VLS) nucleation, followed by the simultaneous radial growth on the sidewalls, and to the end with sidewall transformation during annealing. The VLS nucleation interface of our GaAs nanowires is revealed by examining cross sections of the nanowire, where the nanowire exhibits a Reuleaux triangular shape with three curved surfaces along {112}A. These curved surfaces are not thermodynamically stable and adopt {112}A facets during radial growth. We observe clear differences in radial growth rate between the ⟨112⟩A and ⟨112⟩B directions with {112}B facets forming due to the slower radial growth rate along ⟨112⟩B directions. These sidewalls transform to {110} facets after high temperature (>500 °C) annealing. A nucleation model is proposed to explain the origin of the Reuleaux triangular shape of the nanowires, and the sidewall evolution is explained by surface kinetic and thermodynamic limitations.

19.
Nano Lett ; 14(9): 5206-11, 2014 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-25115241

RESUMO

We report the growth of stacking-fault-free and taper-free wurtzite InP nanowires with diameters ranging from 80 to 600 nm using selective-area metal-organic vapor-phase epitaxy and experimentally determine a quantum efficiency of ∼50%, which is on par with InP epilayers. We also demonstrate room-temperature, photonic mode lasing from these nanowires. Their excellent structural and optical quality opens up new possibilities for both fundamental quantum optics and optoelectronic devices.

20.
Nat Mater ; 12(9): 821-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23812129

RESUMO

The immense potential of colossal permittivity (CP) materials for use in modern microelectronics as well as for high-energy-density storage applications has propelled much recent research and development. Despite the discovery of several new classes of CP materials, the development of such materials with the required high performance is still a highly challenging task. Here, we propose a new electron-pinned, defect-dipole route to ideal CP behaviour, where hopping electrons are localized by designated lattice defect states to generate giant defect-dipoles and result in high-performance CP materials. We present a concrete example, (Nb+In) co-doped TiO2 rutile, that exhibits a largely temperature- and frequency-independent colossal permittivity (> 10(4)) as well as a low dielectric loss (mostly < 0.05) over a very broad temperature range from 80 to 450 K. A systematic defect analysis coupled with density functional theory modelling suggests that 'triangular' In2(3+)Vo(••)Ti(3+) and 'diamond' shaped Nb2(5+)Ti(3+)A(Ti) (A = Ti(3+)/In(3+)/Ti(4+)) defect complexes are strongly correlated, giving rise to large defect-dipole clusters containing highly localized electrons that are together responsible for the excellent CP properties observed in co-doped TiO2. This combined experimental and theoretical work opens up a promising feasible route to the systematic development of new high-performance CP materials via defect engineering.


Assuntos
Modelos Teóricos , Titânio , Condutividade Elétrica , Índio/química , Teste de Materiais , Temperatura , Difração de Raios X
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