The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease

Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers.Methods: We used 11C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study).Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ40 level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups.Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ40 might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis

H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

<p>Abstract</p> <p>Background</p> <p>The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.</p> <p>Results</p> <p>Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in <it>Saccharomyces cerevisiae</it>. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an <it>htb-K123R </it>mutation, leads to synthetic lethality.</p> <p>Conclusion</p> <p>These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.</p

次微米-奈米尺度銅薄膜能量損耗行為與微結構關係之探討

In this study, we use the MEMS process to produce the specimens with silicon substrate, and use this specimens to carry the copper thin film. Combining the capacitance measurement method and vaccum system to advance the dynamic measurement experiment, and studying the mechanical properties of metal thin film. The film carrier is designed to micro-paddle cantilever beam. It can make sure the stress is average in the experiment by using this design. It can improve the accuracy of the results. The vaccum measurement system forces the specimens by static electricity. Using the change of the capacitance to calculate the deformation of the specimens, and then calculate the mechanical properties of metal thin film. This experiment studied the internal friction in different thickness of copper thin film by using the resonant and free decay method. And annealing the specimens to observe the change between before annealing.本研究利用微機電製程在矽基板上製作試件，並利用此試件作為金屬銅薄膜的載具，再利用真空電容量測系統進行動態量測，探討金屬薄膜的機械性質。研究中用於承載銅薄膜的試件是以新式微槳型懸臂樑的設計去製作，這種設計可確保在進行動態檢測時，應力可以均勻分布，使得量測出來的結果更加準確。而真空量測系統是利用靜電力驅動試件，藉由電容的改變量推算出形變量，進而推算出薄膜的機械性質。本研究利用共振衰減法探討不同厚度的銅薄膜對材料內耗的影響，並將試件進行退火處理，觀察與未退火試件的內耗變化。摘要 ..............I 目錄 ..............III 表目錄 ..............VII 圖目錄 ..............VIII 符號說明 .............. XIII 第一章 緒論 ..............1 1.1. 前言..............1 1.2. 研究動機 ..............5 1.2.1. 奈米壓痕法 ..............5 1.2.2. 微型樑彎矩測試法..............6 1.2.3. 鼓膜測試法..............7 1.2.4. 共振測試法 ..............8 1.3. 研究目的 ..............8 1.4. 論文架構..............9 第二章 文獻回顧 ..............10 2.1. 能量損耗機制..............10 2.1.1. 點缺陷鬆弛(point defect relxation) ..............10 2.1.2. 界面鬆弛(interface relaxation) ..............10 2.1.3. 差排鬆弛(dislocation relaxation) ..............11 2.1.4. 熱彈性鬆弛(thermoelastic relaxation) ..............12 2.2. 振動原理 ..............12 2.3. 內耗現象(internal friction) ..............13 2.4. 品質因子(Q factor) ..............14 2.5. 內耗量測與計算 ..............16 2.5.1. 內耗量測方法 ..............16 2.5.2. 內耗計算方法..............19 第三章 試件設計與製程..............22 3.1. 前言..............22 3.2. 試件設計..............22 3.3. 試件製程 ..............25 3.3.1. RCA 洗淨..............27 3.3.2. 沉積氮化矽(SI3N4)薄膜..............28 3.3.3. 微影定義正面圖形..............29 3.3.4. 正面感應耦合電漿蝕刻..............32 3.3.5. 正面光阻去除 ..............33 3.3.6. 微影定義背面圖形.............. 34 3.3.7. 背面感應耦合電漿蝕刻..............34 3.3.8. 光阻去除 ..............34 3.3.9. 利用背面光罩從背面塗佈光阻 ..............35 3.3.10. DEEP RIE (Reactive Ion Etching)深蝕刻 ..............35 3.3.11. 氫氧化鉀(KOH)蝕刻矽晶圓 ..............35 3.3.12. 氫氟酸(HF)去除氮化矽薄膜..............36 3.3.13. 濺鍍(sputter)不同厚鍍之銅薄膜 ..............38 第四章 實驗系統架設 ..............41 4.1. 前言..............41 4.2. 靜電力驅動系統..............41 4.3. 真空電容值量測系統..............43 4.4. 系統內部結構..............46 第五章 結果與討論..............49 5.1. 前言..............49 5.2. 量測步驟介紹 ..............49 5.2.1. 共振頻率量測執行步驟..............50 5.2.2. 衰減率量測執行步驟 ..............54 5.3. 試件與薄膜內耗分析..............56 5.3.1. 純矽試件內耗分析..............56 5.3.2. 鍍銅薄膜試件內耗分析..............61 5.3.3. 退火試片內耗分析..............65 5.3.4. 純銅薄膜與退火銅薄膜內耗分析與比較..............71 5.4. 試件微結構分析..............73 5.4.1. 原子力顯微鏡介紹與分析 ..............73 5.4.2. 掃描式顯微鏡介紹與分析 ..............78 第六章 結論 ..............84 參考文獻 ..............8

Supercritical carbon dioxide anti-solvent purification of anti-oxidative compounds from Lycium barbarum fruits by using response surface methodology

This study employed ultrasonic extraction, column elution fractionation and supercritical anti-solvent (SAS) recrystallization in purifying and in preparing micro-sized particles containing zeaxanthin dipalmitate (ZDP) from the Lycium barbarum fruits. Column fractionation of the ultrasonic acetone extract coupled with the SAS process of the ZDP-laden ethyl-acetate solution enhanced the amount of ZDP to 931.5 mg/g in the SAS precipitates (about 64.9% recovery) compared to 72.25 mg/g from the ultrasonic extract alone. A two-factor experimental design by response surface method showed that feed concentration and feed flow rate were important for SAS in obtaining the highest purity and the smallest mean size of the ZDP particles. The purest ZDP compound (98.3%) also led to the proliferation of anti-hydrogen peroxide oxidation of human adult retinal pigment epithelial cells

Data_Sheet_1_The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease.pdf

<p>Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers.</p><p>Methods: We used ¹¹C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study).</p><p>Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ₄₀ level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ₄₀ level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups.</p><p>Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ₄₀ might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis.</p