Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-beta precursor protein-alpha has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria- related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of alpha-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg2+) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.

gamma-LiAlO2 single crystal grown by Czochralski technique and modified by vapor transport equilibration (VTE) technique

Large-sized (similar to 2 inch, 50.8 mm) gamma-UA102 single crystal has been grown by conventional Czochralski (Cz) method, but the crystal ha's a milky, dendriform center. The samples taken from transparent and milky parts were ground and examined by X-ray diffraction. All diffraction peaks could be indexed in gamma-LiAlO2. The crystal quality was characterized by X-ray rocking curve. The full-width at half-maximum (FWHM) values are 116.9 and 132.0 arcsec for transparent and milky parts, respectively. The vapor transport equilibrium (VTE) technique was introduced to modify the crystal quality. After 1000 degrees C/48 h, 1100 degrees C/48 h, 1200 degrees C/48 h VTE processes, the FWHM values dropped to 44.2 and 55.2 arcsec for transparent and milky part, respectively. The optical transmission of transparent part was greatly enhanced from 85% to 90%, and transmission of milky part from 75% to 80% in the range of 190 similar to 1900 nm at room temperature. When the VTE temperature was raised to 1300 degrees C, the sample cracked and FWHM values of transparent and milky parts were increased to 55.2 and 80.9 arcsec, respectively. By combining Cz technique with VTE technique, large-sized and high quality gamma-LiAlO2 crystal can be obtained.

大尺寸高质量γ-LiAlO2晶体的制备研究

采用提拉法快速（6mm／h）生长了透明、φ45mm×50mm完整的铝酸锂晶体，但晶体中下部出现了一个树状、乳白色的核芯．分别从透明和乳白色核芯部位取样，研磨作粉末X射线衍射测试，发现两个样品所有的衍射峰均可以用γ-LiAlO2指标化．双晶摇摆曲线显示晶体透明和乳白色部位的半高宽分别为116．9arcsec和132．0axcsec，结晶质量较差．通过三步气相传输平衡法（简称VTE）处理后，透明部位半高宽值（FWHM）降至44．2arcsec，乳白色部位FWHM值降至53．3arcsec．结合快速生长和VTE

Comparison of ZnO films grown on before- and after-vapor transport equilibration (VTE) LiAlO2 substrates by pulsed laser deposition (PLD)

About Phi 45 mm LiAlO2 single crystal was grown by Czochralski (Cz) technique. However, the full-width at half-maximum (FWHM) value was high to 116.9 arcsec. After three vapor transport equilibration (VTE) processes, we can obtain high-quality LiAlO2 slice with the FWHM value of 44.2 arcsec. ZnO films were fabricated on as-grown slices and after-VTE ones by pulsed laser deposition (PLD). It was found that ZnO films on the two slices have similar crystallinity, optical transmittance and optical band gap at room temperature. These results not only show that LAO substrate is suitable for ZnO growth, but also prove that the crystal quality of LAO substrate slightly affects the structural and optical properties of ZnO film.

Influence of vapor transport equilibration on the crystal quality and thermal-expansion coefficients of gamma-LiAlO2

gamma-LiAlO2 (LAO) single crystal has been grown by the Czochralski method. However, its quality was deteriorated due to lithium volatilization during the crystal growth. The full width at half maximum value drops from 116.9 to 44.2 arc sec after the LAO slice was treated by vapor transport equilibration at 1000, 1100, and 1200 degrees C/48 h in sequence. The treated slice shows higher optical transmission than the as-grown one in the measured wavelength range of 190-1900 nm, meanwhile, its absorption edge exhibits a blueshift. According to Raman spectra, the treated slice has homogeneous quality at different depths from surface to 0.01 mm. The expansion coefficient of the treated slice for a axis drops from 17.2398x10(-6)/degrees C to 16.5240x10(-6)/degrees C, and that for c axis drops from 10.7664x10(-6)/degrees C to 10.0786x10(-6)/degrees C.

γ-LiAlO2晶体生长、改性和热学性质研究

采用快速提拉法生长出了透明、完整的γ-LIAlO2晶体，但是晶体的高熔点和易挥发性限制了γ-LiAlO2晶体质量．采用气相传输平衡法（vapor transport equilibration technique，VTE）工艺对晶体改性，半高宽（FWHM）值从116．9arcsec降至44．2arcsec，继续升高VTE处理温度至1300℃，FWHM值反而升高至55．2arcsec．快速提拉法生长出来晶体，[100]方向和[001]方向的热膨胀系数分别为17．2398×10^-6／K，10．7664×10

The growth of gamma-LiAlO2 layer with a highly-preferred orientation on (0001) sapphire

Using vapor transport equilibration (VTE) technique we succeeded in the fabrication of single-phase gamma-LiAlO2 layer on (0001) sapphire substrate. X-ray diffraction indicated that the as-fabricated layer was highly textured with [100] orientation at proper VTE treatment temperature range from 1050 degrees C to 1100 degrees C. The main factors affecting the quality of the gamma-LiAlO2 layer were investigated by SEM and transmission spectra. These results reveal the possibility of fabricating gamma-LiAlO2 (100)//sapphire (0001) composite substrate for GaN-based epitaxial film by VTE.

Thermal and electric conductivity of near-zero thermal expansion ZrW 2O8//ZrO2 composites

In this work, the microstructure, thermal and electric conductivity properties of near-zero thermal expansion ZrW2O8/ZrO2 and Al2O3 added ZrW2O8/ZrO2 composites were studied. Both the two composites exhibit very low thermal conductivity and the thermal conductivity decreases slightly as the temperature increases. The electric conductivity of the two composites increases with the increasing of the measurement temperature. The Al2O3 added ZrW2O8/ZrO2 composite has higher thermal and electric conductivity than ZrW2O8/ZrO2 composite. The most important factor which causes the difference of the thermal and electric conductivity of the composites is the porosity. (C) 2008 The Ceramic Society of Japan. All rights reserved.

Subsurface damage in optical substrates

The origin, character, analysis and treatment of subsurface damage (SSD) were summarized in this paper. SSD, which was introduced to substrates by manufacture processes, may bring about the decrease of laser-induced damage threshold (LIDT) of substrates and thin films. Nondestructive evaluation (NDE) methods for the measurement of SSD were used extensively because of their conveniences and reliabilities. The principle, experimental setup and some other technological details were given for total internal reflection microscopy (TIRM), high-frequency scanning acoustic microscopy (HFSAM) and laser-modulated scattering (LMS). However, the spatial resolution, probing depth and theoretic models of these NDE methods demanded further studies. Furthermore, effective surface treatments for minimizing or eliminating SSD were also presented in this paper. Both advantages and disadvantages of ion beam etching (IBE) and magnetorheological finishing (MRF) were discussed. Finally, the key problems and research directions of SSD were summarized. (c) 2005 Elsevier GmbH. All rights reserved.

Design and properties analysis of multi-layer dielectric used in pulse compressor gratings

Used in chirped-pulse amplification system and based on multi-layer thin film stack, pulse compressor gratings (PCG) are etched by ion-beam and holographic techniques. Diffraction efficiency and laser-induced damage threshold rely on the structural parameters of gratings. On the other hand, they depend greatly on the design of multi-layer. A theoretic design is given for dielectric multi-layer, which is exposed at 413.1 nm and used at 1053 nm. The influences of coating design on optical characters are described in detail. The analysis shows that a coating stack of H3L (H2L) (boolean AND) 9H0.5L2.01H meets the specifications of PCG well. And there is good agreement of transmission between experimental and the theoretic design. (c) 2005 Elsevier GmbH. All rights reserved.

A bibliography of Lake Kariba 1987-1994

The bibliography contains some 116 citations, including unpublished reports and manuscripts, regarding Lake Kariba. Most of the reports are from the Zambia/Zimbabwe SADC Fisheries and Lake Kariba Fisheries Research Institute. The citations are listed in alphabetical order according to author.

Sobre la inscripción "HAEp" 2540 procedente de lruña (Álava)

Este trabajo ha sido realizado en el marco del Proyecto de Investigación EHU06/116 «Base de datos epigráfica sobre instrumenta doméstica hallados en el País Vasco». Homenaje a Ignacio Barandiarán Maestu / coord. por Javier Fernández Eraso, Juan Santos Yanguas.