Desenvolvimento e manutenção de memória imunológica após imunização contra Neisseria meningitidis B com a vacina VA-MENGOC-BC

Neisseria meningitidis é uma das principais causas de meningite bacteriana e septicemia em todo o mundo, acometendo principalmente crianças menores de 4 anos. Atualmente, não existe uma vacina universal contra o meningococo B (MenB). A imunidade protetora contra o meningococo caracteriza-se pela presença e persistência de anticorpos bactericidas, porém pouco se sabe sobre os mecanismos de desenvolvimento desta memória sorológica. Avaliamos em modelo animal e em humanos, a geração e manutenção das células secretoras de anticorpos (ASC) e dos linfócitos B de memória (LBm) após vacinação contra MenB. Utilizamos como referência a vacina diftérica (dT ou DTP), considerada ter ótima eficácia em humanos. Para o estudo em modelo animal, grupos de 6 a 8 camundongos suíços, fêmeas, de 5 a 6 semanas, foram imunizados com 3 doses da vacina VA-MENGOC-BC ou DTP, via intramuscular, com intervalo de 2 semanas entre as doses. Aproximadamente 2, 4 ou 6 meses após a última dose, os animais receberam a dose reforço. A vacina anti-MenB induziu uma resposta primária de ASC maior que a resposta à dose reforço. Ao contrário, a resposta de ASC à vacina dT foi maior após o booster. A resposta de LBm anti-MenB permaneceu constante (média de 1%) ao longo de todo o estudo, mas a resposta ao toxóide diftérico (TD) foi maior após o booster (média de 1,9%) que após a imunização primária. A concentração de IgG, anticorpos bactericidas e opsonizantes contra MenB foi dose-dependente e foi reativada após a administração das doses reforços. Esses resultados sugerem que os LBm presentes no baço foram responsáveis pela forte resposta de anticorpos observada após a dose reforço. Para o TD, ambos ASC e LBm foram importantes na manutenção da memória sorológica. Para o estudo em humanos, seis voluntários foram imunizados com 3 doses da vacina VA-MENGOC-BC, via intramuscular, com intervalo de 6 a 7 semanas entre as doses. Seis meses após a imunização primária, os indivíduos receberam uma dose reforço. Outro grupo de voluntários (n = 5) foi imunizado com uma dose reforço da vacina dT. Somente após a terceira dose da vacina anti-MenB foi possível detectar a presença de LBm em todos os indivíduos. Seis meses após a imunização primária, a frequência de LBm voltou ao seu nível basal e não foi reativada após a dose booster. A vacina dT também induziu uma resposta de LBm heterogênea, mas esta foi 5 vezes maior que a induzida por VA-MENGOC-BC. A resposta de anticorpos funcionais anti-MenB foi de curta duração com pequena reativação após a dose reforço. As duas vacinas induziram diferentes frequências de LT de memória central (TCM) e de memória efetora (TEM) após a vacinação primária e após o booster. A resposta à dose booster foi caracterizada pelo aumento da população de linfócitos TCM e diminuição de TEM. A população de linfócitos TCM apresentou maior ativação (CD69+) que os linfócitos TEM, especialmente após a vacinação contra MenB. Concluindo, os dados desta tese indicam que a administração de 3 doses da vacina VA-MENGOC-BC teve uma eficiência limitada em humanos e sugerem que a baixa eficácia da vacina, quando utilizada na década de 90 em São Paulo e no Rio de Janeiro, pode estar relacionada à deficiência na geração e manutenção de LBm específicos.

Preparation, characterization and gas sensing properties of lead tetra-(tert-butyl)-5,10,1 5,20-tetraazaporphyrin spin-coating films

A spin-coated film of lead tetra-(tert-butyl)-5,10,15,20-tetraazaporphyrin complex (PbTAP(t-Bu)(4)) was obtained and characterized by IR spectra, absorption spectra and atomic force microscopy. The response and recovery characteristics of the film to NH3, NO2 and C2H5OH vapor were investigated at room temperature. In addition, the reversibility and stability of the film to NH3 were also studied. The results indicate that the PbTAP(t-Bu)(4) derivative can be exploited as an NH3 sensor at room temperature. (c) 2007 Elsevier B.V. All rights reserved.

Structural change of laser-irradiated Ge2Sb2Te5 films studied by electrical property measurement

Sheet resistance of laser-irradiated Ge2Sb2Te5 thin films prepared by magnetron sputtering was measured by the four-point probe method. With increasing laser power the sheet resistance undergoes an abrupt drop from 10(7) to 10(3) Omega/square at about 580 mW. The abrupt drop in resistance is due to the structural change from amorphous to crystalline state as revealed by X-ray diffraction (XRD) study of the samples around the abrupt change point. Crystallized dots were also formed in the amorphous Ge2Sb2Te5 films by focused short pulse laser-irradiated, the resistivities at the crystallized dots and the non-crystallized area are 3.375 x 10(-3) and 2.725 Omega m, sheet resistance is 3.37 x 10(4) and 2.725 x 10(7) Omega/square respectively, deduced from the I-V Curves that is obtained by conductive atomic force microscope (C-AFM). (C) 2008 Elsevier B.V. All rights reserved.

5.5W CWYb3+ : Y2O3 ceramic laser pumped with 970 nm laser diode

CW laser output has been demonstrated for polycrystalline transparent 10 at.% Yb3+-doped Y2O3 ceramics. End-pumped with 970 nm laser diode, a maximum output power of 5.5 W has been obtained with absorbed pump power of 31.1 W. The slope efficiency is 25% while the threshold pump power is 5.6 W. Saturation is not observed in our experiments, indicating higher laser output can be expected with higher pump power. (C) 2004 Elsevier B.V. All rights reserved.

Dual-wavelength competitive output in Nd:Y3Sc1.5Al3.5O12 ceramic disk laser

In this paper, we demonstrated a dual-wavelength competitive output in Nd:Y3SC1.5Al3.5O12 ceramic disk laser. Different dual-wavelength output behaviors for Nd:YSAG and Nd:YAG ceramic disk laser were investigated and discussed. By applying the energy transfer model, we suggested the reasonable explanation for this new phenomenon as the disordered replacing of Al3+ ions by Sc3+ ions. The main advantage of the dual-wavelength ceramic laser is the possibility to serve as the seed source to generate Terahertz radiation. (C) 2008 Elsevier B.V. All rights reserved.

Spectroscopic properties of Er3+ doped TeO2-BaO (Li2O, Na2O)-La2O3 glasses for 1.5-mu m optical amplifiers

This paper reports on the optical spectroscopic properties and thermal stability of Er3+-doped TeO2-BaO (Li2O,NaO)-La2O3 glasses for developing 1.5-mu m fiber amplifiers. Upon excitation at 977 nm laser diode, an intense 1.53-mu m infrared fluorescence has been observed with a broad full width at half maximum (FWHM) of about 60 nm for the Er3+-doped TeO2-BaO (Li2O, Na2O)-La2O3 glass with 10 mol% of BaO. The calculated fluorescence lifetime and the emission cross-sections of the 1.53-mu m transition are 2.91 ms and similar to 9.97 x 10(-21) cm(2), respectively. It is noted that the gain bandwidth, a, x FWHM, of the TeO2-BaO-La2O3Er2O3 glass is about 600, which is significantly higher than that in silicate and phosphate glasses. Meanwhile, it is interesting to note that the TeO2-BaO-La2O3-Er2O3 glass has shown a high glass thermal stability and good infrared transmittance. As a result, TeO2-BaO (Li2O, Na2O)-La2O3 glass with 10 mol% of BaO has been considered to be more useful as a host for broadband optical fiber amplifier. (c) 2005 Elsevier B.V. All rights reserved.

Photoluminescence of undoped and B-doped ZnO in silicate glasses

Photoluminescence of undoped and B-doped ZnO in silicate glasses was investigated by varying the concentration of ZnO (3550 mol%) and B dopant (0-10 mol%) in the glass matrices. The broad and intense near band edge emissions were observed while the visible light emission was very weak. UV luminescence in all samples was red-shifted relative to the exciton transition in bulk ZnO and enhanced by decreased ZnO concentration due to higher degree of structural integrity and the lower aggregation degree of ZnO. Donor B dopant played the double roles of filling conduction bands to broaden band gap when its concentration was lower than 5 mol%, and emerging with conduction bands to narrow the gap when B dopant exceeded this value. (c) 2007 Elsevier B.V. All rights reserved.

High quantum fluorescence yield of Er3+ at 1.5 mu m in an Yb3+, Ce3+-codoped CaF2 crystal

For the first time, a quaternary doping system of Er3+, Yb3+, Ce3+, Na+:CaF2 single crystal was demonstrated to have high fluorescence yield in the eye-safe 1.5 mu m region under 980 nm laser diode pumping, with relatively broad and flat gain curves. A simplified model was established to illustrate the effect of Ce3+ on the branching ratio for the Er3+4I11/2 -> I-4(13/2) transition. With 0.2-at.% Er3+ and 2.0-at.% Ce3+ in the quaternary-doped CaF2 crystal, the branching ratio was estimated to be improved more than 40 times by the deactivating effect of Ce3+ on the Er3+ 4I11/2 level. The quaternary-doped CaF2, system shows great potential to achieve high laser performance in the 1.5 mu m region. (c) 2006 Elsevier B.V. All rights reserved.

Effects of gamma-irradiation and air annealing on Yb-doped Y3Al5O12 single crystal

The effects of gamma-irradiation on the air-annealed 10 at.% Yb:Y3Al5O12 (YAG) and air annealing on the gamma-irradiated 10at.% Yb:YAG have been studied by the difference absorption spectra before and after treatment. The gamma-irradiation and air annealing led to opposite changes of the absorption properties of the Yb:YAG crystal. After air annealing, the gamma-irradiation induced centers were totally removed and the concentration of Fe3+ and Yb3+ were lightly increased. For the first time, the gamma-irradiation induced valence changes between Yb3+ and Yb2+ ions in Yb:YAG crystals have been observed. (C) 2007 Elsevier B.V. All rights reserved.

Growth and spectral properties of Er:Gd2SiO5 crystal

Er3+ -doped Gd2SiO5 (Er:GSO) single crystal with dimensions of circle divide 35 x 40 mm(3) has been grown by the Czochralski method. The absorption and fluorescence spectra of the Er:GSO crystal were measured at room temperature. The spectral parameters were calculated based on Judd-Ofelt theory, and the intensity parameters Omega(2), Omega(4) and Omega 6 are obtained to be 6.168 x 10(-20), 1.878 x 10(-20), and 1.255 x 10(-20) cm(2), respectively. The emission cross-section has been calculated by Fuechtbauer-Ladenbury formula. (c) 2007 Elsevier B.V. All rights reserved.

Judd-Ofelt analysis of spectra and experimental evaluation of laser performance of Tm3+ doped Lu2SiO5 crystal

This paper reports that the TM3+:Lu2SiO5 (Tm:LSO) crystal is grown by Czochralski technique. The room-temperature absorption spectra of Tm:LSO crystal are measured on a b-cut sample with 4 at.% thulium. According to the obtained Judd-Ofelt intensity parameters Omega(2)=9.3155 x 10(-20) cm(2), Omega(4)=8.4103 x 10(-20) cm(2), Omega(6)=1.5908 x 10(-20) cm(2), the fluorescence lifetime is calculated to be 2.03 ms for F-3(4) -> H-3(6) transition, and the integrated emission cross section is 5.81 x 10(-18) cm(2). Room-temperature laser action near 2 mu m under diode pumping is experimentally evaluated in Tm:LSO. An optical-optical conversion efficiency of 9.1% and a slope efficiency of 16.2% are obtained with continuous-wave maximum output power of 0.67 W. The emission wavelengths of Tm:LSO laser are centred around 2.06 mu m with spectral bandwidth of similar to 13.6 nm.

Bulk crystal growth and efficient diode-pumped laser performance of Yb 3+:Sc2SiO5

A bulk crystal of Yb:Sc2SiO5 (Yb:SSO) with favorable thermal properties was successfully obtained by the Czochralski method. The energy level diagrams for Yb:SSO crystal were determined by optical spectroscopic analysis and semi-empirical crystal-field calculations using the simple overlap model. The full width at half maximum of the absorption band centering at 976 nm was calculated to be 24 nm with a peak absorption cross-section of 9.2x10(-21) cm(2). The largest ground-state splitting of Yb3+ ions is up to 1027 cm(-1) in a SSO crystal host. Efficient diode-pumped laser performance of Yb:SSO was primarily demonstrated with a slope efficiency of 45% and output power of 3.55 W.

Differential activity of GSK-3 isoforms regulates NF-kappa B and TRAIL- or TNF alpha induced apoptosis in pancreatic cancer cells

While TRAIL is a promising anticancer agent due to its ability to selectively induce apoptosis in neoplastic cells, many tumors, including pancreatic ductal adenocarcinoma (PDA), display intrinsic resistance, highlighting the need for TRAIL-sensitizing agents. Here we report that TRAIL-induced apoptosis in PDA cell lines is enhanced by pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) or by shRNA-mediated depletion of either GSK-3 alpha or GSK-3 beta. In contrast, depletion of GSK-3 beta, but not GSK-3 alpha, sensitized PDA cell lines to TNF alpha-induced cell death. Further experiments demonstrated that TNF alpha-stimulated I kappa B alpha phosphorylation and degradation as well as p65 nuclear translocation were normal in GSK-3 beta-deficient MEFs. Nonetheless, inhibition of GSK-3 beta function in MEFs or PDA cell lines impaired the expression of the NF-kappa B target genes Bcl-xL and cIAP2, but not I kappa B alpha. Significantly, the expression of Bcl-xL and cIAP2 could be reestablished by expression of GSK-3 beta targeted to the nucleus but not GSK-3 beta targeted to the cytoplasm, suggesting that GSK-3 beta regulates NF-kappa B function within the nucleus. Consistent with this notion, chromatin immunoprecipitation demonstrated that GSK-3 inhibition resulted in either decreased p65 binding to the promoter of BIR3, which encodes cIAP2, or increased p50 binding as well as recruitment of SIRT1 and HDAC3 to the promoter of BCL2L1, which encodes Bcl-xL. Importantly, depletion of Bcl-xL but not cIAP2, mimicked the sensitizing effect of GSK-3 inhibition on TRAIL-induced apoptosis, whereas Bcl-xL overexpression ameliorated the sensitization by GSK-3 inhibition. These results not only suggest that GSK-3 beta overexpression and nuclear localization contribute to TNF alpha and TRAIL resistance via anti-apoptotic NF-kappa B genes such as Bcl-xL, but also provide a rationale for further exploration of GSK-3 inhibitors combined with TRAIL for the treatment of PDA.

High temperature annealing effect on structure, optical property and laser-induced damage threshold of Ta2O5 films

Ta2O5 films were deposited by conventional electron beam evaporation method and then annealed in air at different temperature from 873 to 1273 K. It was found that the film structure changed from amorphous phase to hexagonal phase when annealed at 1073 K, then transformed to orthorhombic phase after annealed at 1273 K. The transmittance was improved after annealed at 873 K, and it decreased as the annealing temperature increased further. The total integrated scattering (TIS) tests and AFM results showed that both scattering and root mean square (RMS) roughness of films increased with the annealing temperature increasing. X-ray photoelectron spectroscopy (XPS) analysis showed that the film obtained better stoichiometry and the O/Ta ratio increased to 2.50 after annealing. It was found that the laser-induced damage threshold (LIDT) increased to the maximum when annealed at 873 K, while it decreased when the annealing temperature increased further. Detailed damaged models dominated by different parameters during annealing were discussed. (C) 2008 Elsevier B. V. All rights reserved.

Structure and optical properties of Nb2O5 sculptured thin films by glancing angle deposition

Nb2O5 sculptured thin. films deposited by electron beam evaporation with glancing angle deposition were prepared. Nb2O5 sculptured thin. films with tilted columns are optical anisotropy. XRD, SEM, UV-vis-NIR spectra are employed to characterize the microstructure and optical properties. The maximum of birefringence (Delta n) is up to 0.045 at alpha = 70 degrees with packing density of 0.487. With increasing the deposition angle, refractive index and packing density of Nb2O5 STF are decreasing. The relationship among deposition parameter, microstructure and optical properties was investigated in detail. (C) 2008 Elsevier B. V. All rights reserved.