Molecular Characteristics of Amyloid Precursor Protein (APP) and Its Effects in Cancer

Amyloid precursor protein (APP) is a type 1 transmembrane glycoprotein, and its homologs amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are highly conserved in mammals. APP and APLP are known to be intimately involved in the pathogenesis and progression of Alzheimer’s disease and to play important roles in neuronal homeostasis and development and neural transmission. APP and APLP are also expressed in non-neuronal tissues and are overexpressed in cancer cells. Furthermore, research indicates they are involved in several cancers. In this review, we examine the biological characteristics of APP-related family members and their roles in cancer.     

基于C#持久蠕变强度外推功能的实现

持久蠕变强度外推是预测材料在高温高压环境下工作寿命的有效方法。目前常用的外推方法有等温法和参数法。这两种方法都是通过在实验室中采用较短时间的试验，获取试验数据后，通过Excel或者MATLAB等数据处理软件进行数据的拟合处理和外推计算。这些数据归纳统计和数学建模的过程有时需要耗费试验人员的大量精力。介绍了持久蠕变强度外推的软件实现方法，该功能包含在持久蠕变试验设备配备的软件中，试验完成后，软件直接根据试验结果进行数据拟合和持久蠕变强度的外推计算，无需试验数据的统计和建模，大大提高了持久蠕变强度外推计算的效率。     

Prediction models for multiphase-flow-induced corrosion of API X80 steel in CO2/H2S environment

In the offshore oil and gas industry, mainly focusing on the use of rigid or flexible pipes of subsea infrastructure applied to risers or flowlines, one of the greatest difficulties is the interpretation of the combined effects of the various correlated phenomena (hydrodynamic effects of intermittent flow, the effects of corrosivity of the environment in addition to variations in pressure, temperature, and dynamic loading). On the basis of this scenario, defining the degree of severity of each of the correlated system variables becomes of fundamental importance for establishing reliable criteria for selecting materials for subsea application. The established flow pattern directly affects the corrosion rate (or the pipe material mass loss), but the balance of other variables including possible changes in the physical and transported fluid chemical properties may increase the damage up to an order of magnitude, which is a piece of information normally not foreseen in design criteria. Therefore, to improve the understanding of the corrosion study influenced by multiphase flow, a testing loop was designed and assembled at the Corrosion and Protection Laboratory of the Institute for Technological Research, in which API X80 steel coupons were positioned in locations with a 0° and 45° inclinations. Tests were conducted by varying the partial pressure of the gaseous phase containing blends of CO₂ and H₂S with N₂ balance, mixed with the liquid phase containing light oil and heavy oil in water with salinity (NaCl)-simulating oil well conditions with 80% water cut. The main objective of this study is to establish models that can predict the corrosion intensity in conditions close to those obtained experimentally. To achieve results, the multiple regression and Box–Cox transformation methods were applied. These models will make possible damage prediction and optimization of matrix parameters for the multiphase-loop test.     

Split Enzyme-Based Biosensors for Structural Characterization of Soluble and Insoluble β-Glucans

β-Glucan is widely distributed in various plants and microorganisms and is composed of β-1,3-linked d-glucose units. It may have a branched short or long side chain of glucose units with β-1,6- or β-1,4-linkage. Numerous studies have investigated different β-glucans and revealed their bioactivities. To understand the structure-function relationship of β-glucan, we constructed a split-luciferase complementation assay for the structural analysis of long-chain β-1,6-branched β-1,3-glucan. The N- and C-terminal fragments of luciferase from deep-sea shrimp were fused to insect-derived β-1,3-glucan recognition protein and fungal endo-β-1,6-glucanase (Neg1)-derived β-1,6-glucan recognition protein, respectively. In this approach, two β-glucan recognition proteins bound to β-glucan molecules come into close proximity, resulting in the assembly of the full-length reporter enzyme and induction of transient luciferase activity, indicative of the structure of β-glucan. To test the applicability of this assay, β-glucan and two β-glucan recognition proteins were mixed, resulting in an increase in the luminescence intensity in a β-1,3-glucan with a long polymer of β-1,6-glucan in a dose-dependent manner. This simple test also allows the monitoring of real-time changes in the side chain structure and serves as a convenient method to distinguish between β-1,3-glucan and long-chain β-1,6-branched β-1,3-glucan in various soluble and insoluble β-glucans.     

基于云网PoP的弹性边缘网络设计思路探讨

移动边缘云是公司“云+5G”双引擎战略的最佳契合点,边缘网络是发挥移动云“大云”产品和5G网络融合优势,实现云网统筹、构建运营商“连接+计算”核心能力的关键。运营商传统接入网存在云网割裂、分段入云和组网复杂等突出问题,难以适应边缘业务敏捷交付要求。本文通过深入分析边缘云业务特征和技术架构,对标业界主流云商建设实践,研究基于云网PoP网的边缘网络建设思路,创新性提出云网一体化规划设计和建设交付流程变革,基于云网POP统一网络和业务锚点,构建Overlay和Underlay融合双层加速网络架构,探索Spine-leaf化的新型城域接入网实现L3下沉和弹性扩容等方法,实现“云+网+应用”一体化敏捷交付的边缘网络能力。     

The spheroidization process of micron-scaled α-Al2O3 powder in hydrothermal method

Understanding the spheroidization process of micron-scaled α-Al₂O₃ powder in hydrothermal method is of great importance but still not completely revealed. The results demonstrated that SO₄^2? played a significant role in the formation of spherical powder, while the bubble generated from the reaction of urea didn't work in the spheroidization process. The spheroidization process was summed up as two steps. The first was that SO₄^2? limited the hydrolysis of Al³⁺ and reacted with Al³⁺ and OH^- to form Al₄(OH)₁₀SO₄, which nucleated and agglomerated into granular precipitates. The second was Ostwald ripening, which gave the spherical precursors a double-layered structure. When the spherical precursors obtained 120 °C were sintered at 1200 °C, α-Al₂O₃ were got and the spherical morphology still maintained with a large number of nano-sized pores. We anticipate the spherical α-Al₂O₃ with nano-sized pores can be applied in adsorption and filtration industries.     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

Two Methods,One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.