探究现代网络电力电子科技的智能应用

在当代竞争激烈的背景下,电力电子技术的发展决定了一个国家经济的发展,想赢得这场竞争就必须对科学技术进行提升,其中就包括电力电子技术,其不仅具备着滋养的企业发展趋势,还是科学技术水平的一种展现,加上现代电气智能化水平越来越丰富,在电力电子技术的应用就更加广泛。因此,采用智能化网络电力电子科技设备对智能电气设备进行进一步的完善和优化是以后各个国家科技发展的常态。通过智能化网络电子科技设备与智能电气设备完美融合,并且实现电气设备对智能化网络的应用控制,能够更好的将电气设备智能化中的“智能”二字展现的淋漓尽致,由此看来,电力电子科技的智能应用发展趋势将会越来越完美,其发展前景也将在各个领域越来越宽广。</jats:p

對參與阿茲海默症病程發展之大分子間交互作用之研究

阿茲海默症是造成老年失智症的主要原 因之一，它在組織學上的一個病理特徵是在 細胞外會有不溶性的amyloid 斑塊(plaques)出 現，這些amyloid 斑塊主要是由amyloid beta (Aβ) peptide 所組成。由於Aβ peptide 的形成 在整個阿茲海默症病理發展的過程中極早發 生，因此格外吸引研究人員的注意。為了要 對與Aβ生成有關的大分子在體內的正常生理 功能有更深入的了解，我們利用yeast 2-hybrid 系統來找出與這些大分子有著直接接觸的分 子。初步的研究結果顯示，一個代號為aicd59 的integral membrane protein 可能可以和一個 含有Aβ的前驅物(APP)的C 端之59 個氨基酸 的片段(AICD)產生蛋白質-蛋白質間交互作 用。最近已經有一些研究報告指出AICD 可能 與某些基因表現的調控有關，如果我們能證 實aicd59 和AICD 間的交互作用確實存在， 或許能進一步的了解AICD、甚或APP 的正 常生理功能，而對阿茲海默症病理發展的分 子機轉的認識或者也將有所助益

Epi-reevesioside F inhibits Na+/K+-ATPase, causing cytosolic acidification, Bak activation and apoptosis in glioblastoma

Epi-reevesioside F, a new cardiac glycoside isolated from the root of Reevesia formosana, displayed potent activity against glioblastoma cells. Epi-reevesioside F was more potent than ouabain with IC50 values of 27.3 +/- 1.7 vs. 48.7 +/- 1.8 nM (P &lt; 0.001) and 45.0 +/- 3.4 vs. 81.3 +/- 4.3 nM (P &lt; 0.001) in glioblastoma T98 and U87 cells, respectively. However, both Epi-reevesioside F and ouabain were ineffective in A172 cells, a glioblastoma cell line with low Na+/K+-ATPase alpha 3 subunit expression. Epi-reevesioside F induced cell cycle arrest at S and G2 phases and apoptosis. It also induced an increase of intracellular concentration of Na+ but not Ca2+, cleavage and exposure of N-terminus of Bak, loss of mitochondrial membrane potential, inhibition of Akt activity and induction of caspase cascades. Potassium supplements significantly inhibited Epi-reevesioside F-induced effects. Notably, Epi-reevesioside F caused cytosolic acidification that was highly correlated with the anti-proliferative activity. In summary, the data suggest that Epi-reevesioside F inhibits Na+/K+-ATPase, leading to overload of intracellular Na+ and cytosolic acidification, Bak activation and loss of mitochondrial membrane potential. The PI3-kinase/Akt pathway is inhibited and caspase-dependent apoptosis is ultimately triggered in Epi-reevesioside F-treated glioblastoma cells

An Improved Screening Model to Identify Inhibitors Targeting Zinc- Enhanced Amyloid Aggregation

Zinc, which is abundant in senile plaques consisting mainly of fibrillar beta-amyloid (A beta), plays a critical role in the pathogenesis of Alzheimer's disease. Treatment with zinc chelators such as clioquinol has been used to prevent A beta aggregation in Alzheimer's patients; however, clioquinol produces severe side effects. A simple, easy, inexpensive, and versatile screen to identify zinc chelators for inhibition of A beta aggregation is currently unavailable. We thus developed a high-throughput screen that identifies zinc chelators with anti-A beta aggregation activity. The recombinant A beta peptides, aggregated on solid-phase microplates, formed A beta-immunopositive beta- sheet-containing structures in the presence of zinc. Formation of these A beta fibrils was specifically blocked by metal ion chelators. This screening model improves identification of zinc-enhanced A beta fibrils and anti-A beta aggregation mediated by zinc chelating. The convenient system could qualitatively and quantitatively assay a large sample pool for A beta aggregation inhibition and dissolution of All aggregates. This screen is practical, reliable, and versatile for comprehensive detection of amyloid fibrillation and identification of inhibitors of A beta aggregation

FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines

One of the pathological hallmarks of Alzheimer's disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (A beta), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimer's disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the subcellular localization of APP, upon FKBP12 overexpression. This FKBP12-overexpression-induced effect was reverted by FK506. These findings support our hypothesis that FKBP12 may participate in the regulation of APP processing. FKBP12 overexpression may lead to the stabilization of a certain isomer (presumably the cis form) of the Thr668-Pro669 peptide bond in AICD, therefore change its affinity to flotillin-1 or other raft-associated proteins, and eventually change the localization pattern and cause a shift in the proteolytic processing of APP

Trna-Guanine Transglycosylase from Escherichia Coli: Recognition of Noncognate-Cognate Chimeric Trna and Discovery of a Novel Recognition Site within the Tpsic Arm of Trna(Phe)

tRNA-guanine transglycosylase (TGT) is a key enzyme involved in the posttranscriptional modification of tRNA across the three kingdoms of life . In eukaryotes and eubacteria, TGT is involved in the introduction of queuine into the anticodon of the cognate tRNAs. In archaebacteria, TGT is responsible for the introduction of archaeosine into the D-loop of the appropriate tRNAs. The tRNA recognition patterns for the eubacterial ( Escherichia coli) TGT have been studied. These studies are all consistent with a restricted recognition motif involving a U-G-U sequence in a seven- base loop at the end of a helix. While attempting to investigate the potential of negative recognition elements in noncognate tRNAs via the use of chimeric tRNAs, we have discovered a second recognition site for the E . coli TGT in the TpsiC arm of in vitro-transcribed yeast tRNA(Phe). Kinetic analyses of synthetic mutant oligoribonucleotides corresponding to the TpsiC arm of the yeast tRNA(Phe) indicate that the specific site of TGT action is G53 (within a U-G-U sequence at the transition of the TpsiC stem into the loop). Posttranscriptional base modifications in tRNA(Phe) block recognition by TGT, most likely due to a stabilization of the tRNA structure such that G53 is inaccessible to TGT. These results demonstrate hat TGT can recognize the U-G-U sequence within a structural context that is different than the canonical U-G-U in the anticodon loop of tRNA(Asp). Although it is unclear if this second recognition site is physiologically relevant, this does suggest that other RNA species could serve as substrates for TGT in vivo

Calanquinone A induces anti-glioblastoma activity through glutathione-involved DNA damage and AMPK activation

Glioblastoma, a highly malignant glioma, is resistant to both radiation and chemotherapy and is an intractable problem in clinical treatment. New therapeutic approaches are in urgent need. Calanquinone A, an herbal constituent, displayed anti proliferative activity against glioblastoma cells, including A172, T98 and U87. Flow cytometric analysis showed an S phase arrest and a subsequent apoptosis to calanquinone A action. Further identification demonstrated a rapid increase of gamma H2A.X formation at S phase. The data together with comet tail formation and Chk1 activation indicated DNA damage response. N-acetyl cysteine (an antioxidant and a glutathione precursor) and exogenously applied glutathione, but not trolox (an antioxidant), completely abolished calanquinone A-induced effects. Immunofluorescence assay revealed that calanquinone A decreased the intracellular glutathione levels in both A172 and T98 cells. However, calanquinone A. by itself, did not conjugate glutathione. The data suggested that the decrease of cellular glutathione predominantly contributed to the anticancer mechanism. Furthermore, calanquinone A induced the activation of AMP activated protein kinase (AMPK) and the inhibition of p70S6K activity. Rhodamine efflux assay showed that calanquinone A did not block efflux activity, indicating that calanquinone A was not a P-glycoprotein substrate. In summary, the data suggest that calanquinone A displays anti-glioblastoma activity through a decrease of cellular glutathione levels that subsequently induces DNA damage stress and AMPK activation, leading to cell cycle arrest at S-phase and apoptotic cell death. Furthermore, calanquinone A does not serve as a P-glycoprotein substrate, suggesting a potential for further development in anti-glioblastoma therapy. (C) 2014 Elsevier B.V. All rights reserved