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1.
Sci Rep ; 14(1): 6665, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509189

RESUMO

Cu/SiO2 hybrid bonding presents a promising avenue for achieving high-density interconnects by obviating the need for microbumps and underfills. Traditional copper bonding methods often demand temperatures exceeding 400 °C, prompting recent endeavors to mitigate bonding temperatures through investigations into metal passivation bonding. In this study, we scrutinized the diffusion behavior associated with various metal passivation layers (Platinum, Titanium, Tantalum, and Chromium) in the context of low-temperature direct copper bonding and delved into the essential bonding mechanisms. We observed a deviation from conventional metal-metal bonding factors, such as surface roughness and grain size, in the diffusion behavior. Remarkably, our analysis revealed a pronounced correlation between the crystallinity of the metal passivation layers and diffusion behavior, surpassing the influence of other experimental factors. Subsequent post-bonding examinations corroborated consistent diffusion behavior in Pt and Cr passivation samples with disparate crystallinities, reinforcing the significance of crystallinity in the bonding process. Our findings underscore crystallinity as a pivotal factor governing diffusion behavior, even under varied bonding conditions. These insights are instrumental in achieving exceptional bonding characteristics at lower temperatures in Cu/SiO2 hybrid bonding. Implications of this study extend to the prospect of advancing highly integrated systems through die-to-wafer bonding, marking a substantial stride toward future applications.

2.
Metabolism ; 76: 42-55, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28987239

RESUMO

Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-ßl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-ß1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-ß1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-ß1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-ß1-induced collagen production and TGF-ß1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-ß1 and Smad2/3 pathways.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Miocárdio/patologia , Obesidade/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triazóis/farmacologia , Animais , Glicemia , Dieta Hiperlipídica , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Insulina/sangue , Lipídeo A/sangue , Masculino , Miocárdio/metabolismo , Obesidade/complicações , Obesidade/patologia , Ratos , Ratos Endogâmicos SHR , Triazóis/uso terapêutico
3.
Small ; 13(3)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27783457

RESUMO

A 100-nm wide, vertically formed graphene stripe (GS) is demonstrated for three-dimensional (3D) electronic applications. The GS forms along the sidewall of a thin nickel film. It is possible to further scale down the GS width by engineering the deposited thickness of the atomic layer deposition (ALD) Ni film. Unlike a conventional GS or graphene nanoribbon (GNR), the vertically formed GS is made without a graphene transfer and etching process. The process integration of the proposed GS FETs resembles that of currently commercialized vertical NAND flash memory with a design rule of less than 20 nm, implying practical usage of this formed GS for 3D advanced FET applications.

4.
ACS Nano ; 10(7): 7142-6, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27403730

RESUMO

We demonstrate a hybrid integration of a graphene-based analog circuit and a silicon-based digital circuit in order to exploit the strengths of both graphene and silicon devices. This mixed signal circuit integration was achieved using a three-dimensional (3-D) integration technique where a graphene FET multimode phase shifter is fabricated on top of a silicon complementary metal-oxide-semiconductor field-effect transistor (CMOS FET) ring oscillator. The process integration scheme presented here is compatible with the conventional silicon CMOS process, and thus the graphene circuit can successfully be integrated on current semiconductor technology platforms for various applications. This 3-D integration technique allows us to take advantage of graphene's excellent inherent properties and the maturity of current silicon CMOS technology for future electronics.

5.
Arch Pharm Res ; 39(4): 565-576, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26960737

RESUMO

The receptor for advanced glycation end products (RAGE) plays a key role in the development of vascular inflammation and acceleration of atherosclerosis in type 2 diabetes. We investigated the effect of candesartan cilexetil (CDRT) and amlodipine orotate (AMDP) on the expression of RAGE in the aortic walls of Otsuka Long-Evans Tokushima Fatty (OLETF) rats and AGE-treated endothelial cells. Twenty five-week-old OLETF rats were randomized to 8 week treatments consisting of CDRT (n = 8), AMDP (n = 8) or saline (control, n = 8). Immunohistochemical and dihydroethidine staining revealed reduced RAGE and reactive oxygen species (ROS) signals in rats treated with CDRT or AMDP compared with control rats. Both CDRT and AMDP suppressed the expression of p22phox and p47phox NADPH oxidase subunits. However, only CDRT significantly reduced expression of phosphorylated extracellular signal regulated kinase (pERK)1/2 in the aortic wall of OLETF rats. In addition, both drugs reduced RAGE expression and total and mitochondrial ROS production in the AGE-treated endothelial cells. Both ARBs and CCBs reduced RAGE expression in the aortic walls of OLETF rats, which was attributed to decreased ROS production through inhibition of NADPH oxidase. In addition, only CDRT reduced aortic expression of RAGE via suppression of the ERK1/2 pathway unlike AMDP.


Assuntos
Anlodipino/farmacologia , Aorta/efeitos dos fármacos , Benzimidazóis/farmacologia , Compostos de Bifenilo/farmacologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Tetrazóis/farmacologia , Anlodipino/uso terapêutico , Animais , Aorta/enzimologia , Aorta/metabolismo , Benzimidazóis/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/prevenção & controle , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ratos Endogâmicos , Tetrazóis/uso terapêutico
6.
Small ; 12(2): 185-9, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26619270

RESUMO

A graphene thermoacoustic loudspeaker with a thin polymer mesh is fabricated using screen-printing. An experiment with substrates of various free-standing areas shows that a higher sound pressure level can be achieved as compared to previously reported graphene thermoacoustic loudspeakers. Moreover, a modified equation to predict the sound pressure level of the thermoacoustic loudspeaker with a thin and patterned substrate is proposed and verified by experimental results.

7.
Nano Lett ; 14(8): 4352-9, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-24978293

RESUMO

Crystallization of materials has attracted research interest for a long time, and its mechanisms in three-dimensional materials have been well studied. However, crystallization of two-dimensional (2D) materials is yet to be challenged. Clarifying the dynamics underlying growth of 2D materials will provide the insight for the potential route to synthesize large and highly crystallized 2D domains with low defects. Here, we present the growth dynamics and recrystallization of 2D material graphene under a mobile hot-wire assisted chemical vapor deposition (MHW-CVD) system. Under local but sequential heating by MHW-CVD system, the initial nucleation of nanocrystalline graphenes, which was not extended into the growth stage due to the insufficient thermal energy, took a recrystallization and converted into a grand single crystal domain. During this process, the stitching-like healing of graphene was also observed. The local but sequential endowing thermal energy to nanocrystalline graphenes enabled us to simultaneously reveal the recrystallization and healing dynamics in graphene growth, which suggests an alternative route to synthesize a highly crystalline and large domain size graphene. Also, this recrystallization and healing of 2D nanocrystalline graphenes offers an interesting insight on the growth mechanism of 2D materials.

8.
J Nanosci Nanotechnol ; 14(11): 8365-71, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958529

RESUMO

The final aim of this study was to confirm the neuroprotective effects of recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their effects with those of rhEPO using an in vitro model of cerebral ischemia. Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). In addition, significant intracellular uptake of these particles was monitored by confocal microscopy. Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI) staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any concentration investigated and rescued more neuronal cells, while preserving normocytic features against glutamate-induced excitotoxic damages compared to rhEPO.


Assuntos
Eritropoetina/farmacologia , Ácido Glutâmico/toxicidade , Nanopartículas/química , Fármacos Neuroprotetores/farmacologia , Colato de Sódio/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Estabilidade de Medicamentos , Eritropoetina/química , Humanos , Ácido Láctico/química , Neuroblastoma , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacologia
9.
J Nanosci Nanotechnol ; 14(11): 8390-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25958534

RESUMO

Different concentrations of estradiol (E2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (E2-PLGA-NPs) were synthesized using the emulsion-diffusion method. Transmission electron microscopy results showed that the average particle size of E2-PLGA-NPs was 98 ± 1.9 nm when stabilized with polyvinyl alcohol and 103 ± 4.9 nm when stabilized with Tween-80. Fourier transform-infrared spectroscopy with diamond attenuated total reflectance was used to identify the presence or absence of E2 molecules in PLGA nanocapsules. Cell proliferation was assessed after treating SH-SY5Y neuroblastoma cells with 1 nM-1 µM of E2 and E2-PLGA-NPs. The neuroprotective efficacy against glutamate-induced excitotoxicity was also investigated in SH-SY5Y neuroblastoma cells. Neuroprotection was greater in E2-PLGA-NP-treated cells than in cells treated with the same concentration of E2. Furthermore, E2- and E2-PLGA-NP-treated cells expressed more p-ERK1/2 and p-CREB than cells treated with glutamate only. Moreover, the expression of p-ERK1/2 was higher than that of p-CREB. In this study, p-ERK1/2 had a greater influence on the neuroprotective effect of E2 and E2-PLGA-NPs than p-CREB.


Assuntos
Estradiol/farmacologia , Ácido Glutâmico/toxicidade , Ácido Láctico/química , Nanopartículas/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ácido Poliglicólico/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Emulsões , Estradiol/química , MAP Quinases Reguladas por Sinal Extracelular/análise , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Nanotecnologia , Neurônios/citologia , Fármacos Neuroprotetores/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
10.
Nanotechnology ; 23(45): 455704, 2012 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-23085718

RESUMO

We report the first experimental results on the electromagnetic interference (EMI) shielding effectiveness (SE) of monolayer graphene. The monolayer CVD graphene has an average SE value of 2.27 dB, corresponding to ~40% shielding of incident waves. CVD graphene shows more than seven times (in terms of dB) greater SE than gold film. The dominant mechanism is absorption rather than reflection, and the portion of absorption decreases with an increase in the number of graphene layers. Our modeling work shows that plane-wave theory for metal shielding is also applicable to graphene. The model predicts that ideal monolayer graphene can shield as much as 97.8% of EMI. This suggests the feasibility of manufacturing an ultrathin, transparent, and flexible EMI shield by single or few-layer graphene.

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