878 resultados para HIGH-DENSITY LIPOPROTEIN (HDL)


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Sphingolipids are essential components of cell membranes, and many of them regulate vital cell functions. In particular, ceramide plays crucial roles in cell signaling processes. Two major actions of ceramides are the promotion of cell cycle arrest and the induction of apoptosis. Phosphorylation of ceramide produces ceramide 1-phosphate (C1P), which has opposite effects to ceramide. C1P is mitogenic and has prosurvival properties. In addition, C1P is an important mediator of inflammatory responses, an action that takes place through stimulation of cytosolic phospholipase A2, and the subsequent release of arachidonic acid and prostaglandin formation. All of the former actions are thought to be mediated by intracellularly generated C1P. However, the recent observation that C1P stimulates macrophage chemotaxis implicates specific plasma membrane receptors that are coupled to Gi proteins. Hence, it can be concluded that C1P has dual actions in cells, as it can act as an intracellular second messenger to promote cell survival, or as an extracellular receptor agonist to stimulate cell migration.

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The interaction of a petawatt laser with a small solid-density plasma bunch is studied by particle-in-cell simulation. It is shown that when irradiated by a laser of intensity >10(21) W/cm(2), a dense plasma bunch of micrometer size can be efficiently accelerated. The kinetic energy of the ions in the high-density region of the plasma bunch can exceed ten MeV at a density in the 10(23)-cm(-3) level. Having a flux density orders of magnitude higher than that of the traditional charged-particle pulses, the laser-accelerated plasma bunch can have a wide range of applications. In particular, such a dense energetic plasma bunch impinging on the compressed fuel in inertial fusion can significantly enhance the nuclear-reaction cross section and is thus a promising alternative for fast ignition.

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The search for reliable proxies of past deep ocean temperature and salinity has proved difficult, thereby limiting our ability to understand the coupling of ocean circulation and climate over glacial-interglacial timescales. Previous inferences of deep ocean temperature and salinity from sediment pore fluid oxygen isotopes and chlorinity indicate that the deep ocean density structure at the Last Glacial Maximum (LGM, approximately 20,000 years BP) was set by salinity, and that the density contrast between northern and southern sourced deep waters was markedly greater than in the modern ocean. High density stratification could help explain the marked contrast in carbon isotope distribution recorded in the LGM ocean relative to that we observe today, but what made the ocean's density structure so different at the LGM? How did it evolve from one state to another? Further, given the sparsity of the LGM temperature and salinity data set, what else can we learn by increasing the spatial density of proxy records?

We investigate the cause and feasibility of a highly and salinity stratified deep ocean at the LGM and we work to increase the amount of information we can glean about the past ocean from pore fluid profiles of oxygen isotopes and chloride. Using a coupled ocean--sea ice--ice shelf cavity model we test whether the deep ocean density structure at the LGM can be explained by ice--ocean interactions over the Antarctic continental shelves, and show that a large contribution of the LGM salinity stratification can be explained through lower ocean temperature. In order to extract the maximum information from pore fluid profiles of oxygen isotopes and chloride we evaluate several inverse methods for ill-posed problems and their ability to recover bottom water histories from sediment pore fluid profiles. We demonstrate that Bayesian Markov Chain Monte Carlo parameter estimation techniques enable us to robustly recover the full solution space of bottom water histories, not only at the LGM, but through the most recent deglaciation and the Holocene up to the present. Finally, we evaluate a non-destructive pore fluid sampling technique, Rhizon samplers, in comparison to traditional squeezing methods and show that despite their promise, Rhizons are unlikely to be a good sampling tool for pore fluid measurements of oxygen isotopes and chloride.

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We describe high-efficiency diffraction gratings fabricated in fused silica at the wavelength of 632.8 nm by rigorous coupled-wave analysis (RCWA). High-density holographic gratings, if the groove density falls within the range of 1575-1630 lines/mm and the groove depth within the range of 1.1-1.3 microns, can realize high diffraction efficiencies at the wavelength of 632.8 nm, e.g., the first Bragg diffraction efficiency can theoretically achieve more than 93% both in TE- and TM-polarized incidences, which greatly reduces the polarization-dependent losses. Note that with different groove profiles further optimized, the maximum efficiency of more than 99.69% can be achieved for TM-polarized incidence, or 97.81% for TE-polarized incidence.

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High-density optical data storage requires high-numerical-aperture (NA) lenses and short wavelengths, But, with increasing NA and decreasing wavelength, the depth of focus (DOF) decreases rapidly. We propose to use pure-phase superresolution apodizers to optimize the axial intensity distribution and extend the DOF of an optical pickup. With this kind of apodizer, the expected DOF can be 2-4.88 times greater than that of the original system, and the spot size will be smaller than that of the original system. (C) 2001 Optical Society of America.

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Eu2+-doped high silica glass (HSG) is fabricated by sintering porous glass which is impregnated with europium ions. Eu2+-doped HSG is revealed to yield intense blue emission excited by ultraviolet (UV) light and near-infrared femtosecond laser. The emission profile obtained by UV excitation can be well traced by near-infrared femtosecond laser. The upconversion emission excited by 800 nm femtosecond laser is considered to be related to a two-photon absorption process from the relationship between the integrated intensity and the pump power. A tentative scheme of upconverted blue emission from Eu2+-doped HSG was also proposed. The HSG materials presented herein are expected to find applications in high density optical storage and three-dimensional color displays. (c) 2008 American Institute of Physics.

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Lipoproteins are responsible for cholesterol traffic in humans. Low density lipoprotein (LDL) delivers cholesterol from liver to peripheral tissues. A misleading delivery can lead to the formation of atherosclerotic plaques. LDL has a single protein, apoB-100, that binds to a specific receptor. It is known that the failure associated with a deficient protein-receptor binding leads to plaque formation. ApoB-100 is a large single lipid-associated polypeptide difficulting the study of its structure. IR spectroscopy is a technique suitable to follow the different conformational changes produced in apoB-100 because it is not affected by the size of the protein or the turbidity of the sample. We have analyzed LDL spectra of different individuals and shown that, even if there are not big structural changes, a different pattern in the intensity of the band located around 1617 cm 21 related with strands embedded in the lipid monolayer, can be associated with a different conformational rearrangement that could affect to a protein interacting region with the receptor.

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As estatinas são fármacos inibidores competitivos da enzima hidroxi-3-metil-glutaril Coenzima A (HMGCoA) redutase, amplamente utilizados para o controle da hipercolesterolemia total e, em especial, para a redução dos níveis séricos de LDLc (Low Density Lipoprotein cholesterol). Além do efeito primário, esses fármacos apresentam vários efeitos secundários, chamados de efeitos pleiotrópicos, envolvendo atividade anti-inflamatória, antitumoral e antiparasitária. Para o desenvolvimento de inovações na área de química medicinal é imprescindível avaliar o risco de efeitos adversos para saúde ou, em outras palavras, a segurança terapêutica do novo produto nas condições propostas de uso. Nesse sentido, o objetivo desse trabalho foi investigar a genotoxicidade de quatro análogos inibidores da biossíntese de lipídios, da classe das estatinas, em modelos experimentais in vitro, testados previamente contra o clone W2 de Plasmodium falciparum a fim de se obter o IC50 dessas moléculas frente ao patógeno. Foram desenvolvidas quatro novas moléculas (PCSR02.001, PCSR09.001, PCSR08.002 e PCSR10.002). Para a avaliação da toxicidade, foram realizados o teste de mutagenicidade bacteriana (teste de Ames), o ensaio de viabilidade celular utilizando o reagente WST-1 e o ensaio de indução de micronúcleos, ambos utilizando uma linhagem ovariana (CHO-K1) e uma linhagem hepática (HepG2). Levando em conta o fato de nenhuma das amostras ter induzido efeitos mutagênicos nas linhagens de S. enterica sorovar Typhimurium, e PCSR10.002 ter apresentado citotoxicidade sugere-se então que este composto seja o mais tóxico. Comparativamente, PCSR10.002 foi mais genotóxico e citotóxico para a linhagem CHO-K1 do que para a linhagem HepG2. PCSR02.001 apresentou elevado potencial genotóxico para células ovarianas, mas não foi capaz de induzir a formação de micronúcleos em células hepáticas, apresentando, portanto um perfil similar ao observado em PCSR10.002. Assim como a atorvastatina, PCSR09.001 apresentou elevado potencial pró-apoptótico para a linhagem de hepatócitos. Já PCSR08.002, apresentou aumento na apoptose de CHO-K1. A indução de apoptose não é necessariamente um evento negativo, já que é pouco lesiva e responsável pela eliminação de células danificadas. Porém, as respostas de apoptose induzidas por esse composto foram muito inferiores àquelas induzidas pela atorvastatina (cerca de 4 vezes menor que a atorvastatina). PCSR08.002 foi aquele se mostrou menos tóxico e essa amostra foi a que teve menor risco relativo, em uma análise global das respostas de citotoxicidade e não demonstrou ter potencial genotóxico para as linhagens utilizadas nesse estudo. Conclui-se, portanto, que a análise da atividade toxicológica utilizando modelos experimentais in vitro dessas estatinas constitui um importante passo para o estabelecimento de novos candidatos à fármacos com maior segurança.

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É um desafio na sociedade moderna controlar a obesidade e comorbidades associadas na população. O objetivo do estudo foi avaliar o impacto do treinamento intervalado de alta intensidade no contexto da obesidade induzida por dieta em modelo animal. Camundongos C57BL/6 foram alimentados com ração padrão (grupo magro - LE) ou dieta rica em gordura (grupo obeso - OB). Após 12 semanas, os animais foram divididos em grupos não treinados (LE-NT e OB-NT) e grupos treinados (LE-T e OB-T) e teve início um protocolo de exercício. Nos grupos treinados em comparação aos grupos não treinados observou-se que o treinamento intervalado de alta intensidade levou a reduções significativas na massa corporal, glicemia e tolerância oral à glicose, colesterol total, triglicérides, lipoproteína de baixa densidade-colesterol, aspartato transaminase e alanina aminotransferase no fígado. Além disso, nos grupos treinados, o protocolo de exercício melhorou a imunodensidade de insulina nas ilhotas, reduziu os níveis de citocinas inflamatórias, adiposidade e esteatose hepática. O treinamento de alta intensidade melhorou a beta-oxidação e os níveis de receptores ativados por proliferador de peroxissomo (PPAR)-alfa e reduziu os níveis de lipogênese e de PPAR-gama no fígado. No músculo esquelético, o treinamento de alta intensidade também melhorou o PPAR-alfa e transportador de glicose (GLUT) -4 e reduziu os níveis de PPAR-gama. Esses achados reforçam a noção de que o treinamento de alta intensidade é relevante como uma abordagem não farmacológica para controlar a resistência à insulina, glicemia, e esteatose hepática. Em conclusão, treinamento de alta intensidade leva à perda de massa corporal e pode atenuar os efeitos adversos causados pela ingestão crônica de uma dieta rica em gordura. Apesar de uma ingestão contínua dessa dieta, o treinamento de alta intensidade melhora as enzimas hepáticas e o perfil inflamatório.

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This paper demonstrates and discusses novel "three dimensional" silicon based junction isolation/termination solutions suitable for high density ultra-low-resistance Lateral Super-Junction structures. The proposed designs are both compact and effective in safely distributing the electrostatic potential away from the active device area. The designs are based on the utilization of existing layers in the device fabrication line, hence resulting in no extra complexity or cost increase. The study/demonstration is done through extensive experimental measurements and numerical simulations. © 2012 IEEE.

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A modified gel-casting technique was used to fabricate a 1-3 piezoelectric ceramic/polymer composite substrate formed by irregular-shaped pillar arrays of small dimensions and kerfs. This technique involves the polymerization of aqueous piezoelectric (PZT) suspensions with added water-soluble epoxy resin and polyamine-based hardener that lead to high strength, high density and resilient ceramic bodies. Soft micromoulding was used to shape the ceramic segments, and micropillars with lateral features down to 4 m and height-to-width aspect ratios of ∼10 were achieved. The composite exhibited a clear thickness resonance mode at approximately 70 MHz and a k eff ∼ 0.51, demonstrating that the ceramic micropillars possess good electrical properties. Furthermore, gel-casting allows the fabrication of ceramic structures with non-conventional shapes; hence, device design is not limited by the standard fabrication methods. This is of particular benefit for high-frequency transducers where the critical design dimensions are reduced. © 2012 IOP Publishing Ltd.

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High-power and broadband quantum-dot (QD) superluminescent light-emitting diodes are realized by using a combination of self-assembled QDs with a high density, large inhomogeneous broadening, a tapered angled pump region, and etched V groove structure. This broad-area device exhibits greater than 70-nm 3-dB bandwidth and drive current insensitive emission spectra with 100-mW output power under continuous-wave operation. For pulsed operation, greater than 200-mW output power is obtained.

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Low-indium-content self-assembled InGaAs/GaAs quantum dots (SAQD) were grown using solid-source molecular beam epitaxy (MBE) and investigated by atomic force microscopy and photoluminescence (PL) spectroscopy. Silicon, which was doped at different quantum dot (QD) growth stages, markedly increased the density of QD. We obtained high density In0.35Ga0.65As/GaAs(001) quantum dots of 10(11)/cm(2) at a growth temperature of 520degreesC. PL spectra and distribution statistics show the high quality and uniformity of our silicon-doped samples. The density increment can be explained using the lattice-hardening mechanism due to silicon doping.

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The effects of InP substrate orientations on self-assembled InAs quantum dots (QDs) have been investigated by molecular beam epitaxy (MBE). A comparison between atomic force microscopy (AFM) and photoluminescence (PL) spectra shows that a high density of smaller InAs islands can be obtained by using such high index substrates. On the other hand, by introducing a lattice-matched underlying In0.52Al0.24Ga0.24As layer, the InAs QDs can be much more uniform in size and have a great improvement in PL properties. More importantly, 1.55-mu m luminescence at room temperature (RT) can be realized in InAs QDs deposited on (001) InP substrate with underlying In0.52Al0.24Ga0.24As layer. (C) 2000 Elsevier Science B.V. All rights reserved.