FTY720 attenuates excitotoxicity and neuroinflammation

Background: FTY720 (fingolimod, Gilenya(TM)), a structural analog of sphingosine-1-phosphate (S1P), is the first oral drug approved for treatment the relapsing-remitting form of multiple sclerosis (MS), and its efficacy has been related to induced lymphopenia and consequent immunosuppression via modulation of S1P(1) receptors (S1P(1)R). However, due to its lipophilic nature, FTY720 crosses the blood brain barrier (BBB) and could act directly on neural cells. In this study, we investigated the effectiveness of FTY720 as a neuroprotective agent using in vitro and in vivo models of excitotoxic neuronal death and examined if FTY720 exerts a direct action on neurons, or/and an indirect modulation of inflammation-mediated neurodegeneration as a possible mechanism of neuroprotection. Methods: Primary neuronal and organotypic cortical cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic cell death (measured by lactate dehydrogenase (LDH) assay or propidium iodide uptake, respectively). The effects of FTY720 treatment (10, 100 and 1,000 nM) on neuronal survival were examined. As an in vivo model of neuronal death and inflammation, we used intracerebroventricular (icv) administration of kainic acid (KA; 0.5 mu g/2 mu l) in Sprague-Dawley rats. FTY720 was applied icv (1 mu g/2 mu l), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days after icv. Rats were evaluated for neurological score, neuronal loss in CA3 hippocampal region and activation of microglia at the lesion site. In addition, we tested FTY720 as a modulator of microglia responses using microglial cell cultures activated with lipopolysaccharide (LPS) and its effects in stress signalling pathways using western blotting for p38 and JNK1/2 mitogen-activated protein kinases (MAPKs). Results: FTY720 was able to reduce excitotoxic neuronal death in vitro. Moreover, in vivo repeated FTY720 administration attenuated KA-induced neurodegeneration and microgliosis at the CA3 lesion site. Furthermore, FTY720 negatively modulates p38 MAPK in LPS-activated microglia, whereas it had no effect on JNK1/2 activation. Conclusions: These data support a role for FTY720 as a neuroprotective agent against excitotoxin-induced neuronal death and as a negative modulator of neuroinflammation by targeting the p38 MAPK stress signalling pathway in microglia.

提拉法Tm：YAG晶体的生长缺陷研究

采用提拉法(CZ)生长了质量优异的Tm：YAG晶体．部分晶片在1000℃的空气气氛中退火25h．借助光学显微镜、扫描电子显微镜(SEM)，结合化学腐蚀法，对Tm：YAG晶体退火前后(111)面的缺陷特征进行了研究．Tm：YAG晶体(111)面的位错腐蚀坑呈三角形．在偏光显微镜下观察了退火前后Tm：YAG晶体(111)面的应力双折射．同时应用高分辨X射线衍射法测定了晶体的完整性．实验结果表明，长时间空气气氛下高温退火有效降低了晶体中总的位错密度，提高了晶体质量．

Efficient diode-pumped Tm : YALO(3) laser with a pump recycling scheme

By using a pump recycling configuration, the maximum power of 8.1 W in the wavelength range 1.935-1.938 mu m is generated by a 5-mm long Tm:YAlO3 (4 at. %) laser operating at 18 degrees C with a pump power of 24 W. The highest slope efficiency of 42% is attained, and the pump quantum efficiency is up to 100%. The Tm:YAlO3 laser is employed as a pumping source of singly-doped Ho(l%):GdVO4 laser operating at room temperature, in which continuous wave output power of greater than 0.2 W at 2.05 mu m is achieved with a slope efficiency of 9%.

Infrared to visible upconversion fluorescence in Yb,Tm : YAG single crystal

Absorption spectrum from 400 to 2000 run and upconversion fluorescence spectra under 940 nm pumping of YAG single crystal codoped with 5 at.% Yb3+ and 4 at.% Tm3+ were studied at room temperature. The blue upconversion emission centered at 483 nm corresponds to the transition (1)G(4) -> H-3(6), the emission band around 646 nm corresponds to the transition (1)G(4) -> F-3(4) of Tm3+. Energy transfer from Yb3+ to Tm3+ is mainly nonradiative and the transfer efficiency was experimentally assessed. The line strengths, transition probabilities and radiative lifetimes of (1)G(4) level were calculated by using Judd-Ofelt theory. Gain coefficient calculated from spectra shows that the upconversion corresponding with transitions (1)G(4) -> H-3(6) in YAG doped with Yb3+ and Tm3+ is potentially useful for blue light Output. (c) 2006 Elsevier B.V. All rights reserved.

高效室温下激光二极管泵浦Tm:YAP激光器

文章报道了室温下二极管泵浦Tm：YAP激光器，最大输出功率5.2瓦，波长为1981nm，斜率效率是30％。实验测量800nm左右晶体的吸收谱以及1800nm附近的荧光发射谱。此外，讨论了输出功率随晶体工作温度关系。

Tm:Y_2SiO_5晶体的生长和光谱性质研究

采用中频感应提拉法生长了高质量的Tm:Y2SiO5(Tm:YSO)晶体,测定了晶体的晶格常数和分凝系数.运用劳厄照相法确定了单斜晶系Tm:YSO晶体的三个偏振轴〈010〉,D1和D2,在室温下测量了三个偏振轴方向的吸收光谱、荧光光谱和荧光寿命,计算了晶体吸收峰的吸收线宽和吸收截面.研究发现,相对于其他两个偏振轴方向,D1方向在790 nm处出现较强的吸收峰,同时在2μm附近出现了一定强度的发射峰,D1方向的吸收截面较大,荧光寿命较长.Tm:YSO晶体适用于AlGaAs二极管抽运固体激光器,在2μm波段固体激光器的应用上将有很大的发展潜力.

利用窄得-奥菲特理论研究Tm:Lu_2SiO_5晶体的光谱特性

采用丘克拉斯基(Czochralski)技术生长了掺铥硅酸镥(Tm∶Lu2SiO5,Tm∶LSO)晶体;测量了LSO晶体在室温下的非偏振吸收光谱和非偏振荧光光谱;利用窄得-奥菲特(Judd-Ofelt)理论计算了Tm∶LSO晶体的窄得-奥菲特强度参数、振子强度、自发辐射概率、辐射寿命、积分吸收截面和积分发射截面.Tm∶LSO晶体的强度参数为Ω2=9.1355×10-20cm2,Ω4=8.4103×10-20cm2,Ω6=1.5908×10-20cm2;Tm∶LSO晶体在1.9μm附近有明显的发射峰(3F4→3H6跃迁),相应的辐射寿命为2.03 ms,积分发射截面为5.81×10-18cm2,半峰全宽(FWHM)为250 nm.用Tm∶LSO晶体在77 K温度下实现了激光运转.利用792 nm的激光二极管(LD)作为抽运源,获得中心波长为1960 nm的激光输出,抽运阈值为2.13 kW/cm2.

Continuous-wave and Q-switched operation of a resonantly pumped Ho:YAlO3 laser

We demonstrated continuous-wave ( CW) and Q-switched operation of a room-temperature Ho: YAlO3 laser that is resonantly end-pumped by a diode-pumped Tm: YLF laser at 1.91 mu m. The CW Ho: YAlO3 laser generated 5.5 W of linearly polarized (E parallel to c) output at 2118 nm with beam quality factor of M-2 approximate to 1.1 for an incident pump power of 13.8 W, corresponding to optical-to-optical conversion efficiency of 40%. Up to 1-mJ energy per pulse at pulse repetition frequency (PRF) of 5 kHz, and the maximum average power of 5.3-W with FWHM pulse duration of 30.5 ns at 20 kHz were achieved in Q-switched mode. (C) 2008 Optical Society of America.

Diode-pumped Q-switched Tm:YAP laser with a pump recycling scheme

We reported on a diode end-pumped AO Q-switched Tm:YAP laser at 1937 nm. The average output power was 3.9 W, with a slope efficiency of 29.4% and optical-optical conversion efficiency of 21.6% at a 5-kHz repetition rate. The temperature dependency of the output power and the pulse width at different repetition rates were investigated in details.

Empowering natives through autobiographical writing: Lee Maracles Bobbi Lee indian rebel and Leslie Marmon Silkos The turquoise ledge: a memoir

Esta dissertação trata de duas obras autobiográficas escritas por autoras nativas que ganharam reconhecimento na década de 70: Bobbi Lee Indian Rebel (1975), da nativo-canadense Lee Maracle, e The Turquoise Ledge: a Memoir (2010), da nativo-americana Leslie Marmon Silko. A importância destas autoras para a Renascença Nativo-Americana/Canadense é inegável, e cada uma delas contribuiu fazendo uso de estratégias diferentes: enquanto Maracle começou sua carreira com Bobbi Lee Indian Rebel, de cunho autobiográfico, Silko esperou mais de trinta anos para publicar The Turquoise Ledge. A problematização de se ver estas obras pelo olhar estritamente ocidental, ou estritamente nativo, é discutida, assim como o aparentemente inevitável tom político dessas narrativas. Ainda que mais de três décadas separem a publicação das obras selecionadas, perguntas como: Estas obras podem ser consideradas literatura?, Elas têm como principal propósito engrandecer feitos pessoais das autoras?, ou Como essas narrativas contribuem para o empoderamento do povo Nativo? podem nunca chegar a serem respondidas, mas, de fato, incitaram a escrita desta dissertação e nortearam nossa análise