Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Endothelial Glycocalyx as a Regulator of Fibrotic Processes

The endothelial glycocalyx, the gel layer covering the endothelium, is composed of glycosaminoglycans, proteoglycans, and adsorbed plasma proteins. This structure modulates vessels’ mechanotransduction, vascular permeability, and leukocyte adhesion. Thus, it regulates several physiological and pathological events. In the present review, we described the mechanisms that disturb glycocalyx stability such as reactive oxygen species, matrix metalloproteinases, and heparanase. We then focused our attention on the role of glycocalyx degradation in the induction of profibrotic events and on the possible pharmacological strategies to preserve this delicate structure.     

Utilizing sensor data to model students’ creativity in a digital environment

While creativity is essential for developing students’ broad expertise in Science, Technology, Engineering, and Math (STEM) fields, many students struggle with various aspects of being creative. Digital technologies have the unique opportunity to support the creative process by (1) recognizing elements of students’ creativity, such as when creativity is lacking (modeling step), and (2) providing tailored scaffolding based on that information (intervention step). However, to date little work exists on either of these aspects. Here, we focus on the modeling step. Specifically, we explore the utility of various sensing devices, including an eye tracker, a skin conductance bracelet, and an EEG sensor, for modeling creativity during an educational activity, namely geometry proof generation. We found reliable differences in sensor features characterizing low vs. high creativity students. We then applied machine learning to build classifiers that achieved good accuracy in distinguishing these two student groups, providing evidence that sensor features are valuable for modeling creativity.     

气管上段腺样囊性癌的临床病理

目的　探讨气管上段腺样囊性癌的临床病理特征及诊断和鉴别诊断要点。方法　收集2000年1月至2014年2月在北京协和医院确诊的4例气管上段腺样囊性癌病例，通过光镜、免疫组织化学及组织化学染色分析其临床病理特征、免疫组织化学特点、诊断及鉴别诊断要点。结果　4例气管上段腺样囊性癌患者中，男1例，女3例，平均年龄47岁(38~57岁）；既往均无腺样囊性癌病史，1例患者既往有结节性甲状腺肿手术史。镜下检查4例均为筛状/管状型腺样囊性癌，3例累及甲状腺组织，3例累及神经组织，未见淋巴结受累。免疫组织化学染色示4例P16、CD117、BCL2、P63、SMA均阳性，Ki67指数平均8%，TTF1和P53均阴性；4例中基底膜样物胶原Ⅳ阳性；组织化学染色示AB/PAS阳性。术后均接受总剂量为48~56 Gy的放疗，随访6~120个月，平均72.5个月，1例术后96个月复发，3例随访期间无复发及转移。结论　气管上段腺样囊性癌是罕见的原发于气管的低度恶性肿瘤，肿瘤生长缓慢，就诊时多数已侵及甲状腺组织，需要与原发于甲状腺的恶性肿瘤相鉴别，特别是在甲状腺穿刺及术中冰冻检查时。结合电子喉气管镜下表现、典型的形态学及免疫组织化学和组织化学染色有助于准确诊断。手术难以切除干净，术后放疗对延缓疾病复发有一定帮助。     

Proton-Detected Solid-State NMR of the Cell-Free Synthesized α-Helical Transmembrane Protein NS4B from Hepatitis C Virus

Proton-detected 100 kHz magic-angle-spinning (MAS) solid-state NMR is an emerging analysis method for proteins with only hundreds of microgram quantities, and thus allows structural investigation of eukaryotic membrane proteins. This is the case for the cell-free synthesized hepatitis C virus (HCV) nonstructural membrane protein 4B (NS4B). We demonstrate NS4B sample optimization using fast reconstitution schemes that enable lipid-environment screening directly by NMR. 2D spectra and relaxation properties guide the choice of the best sample preparation to record 2D ¹H-detected ¹H,¹⁵N and 3D ¹H,¹³C,¹⁵N correlation experiments with linewidths and sensitivity suitable to initiate sequential assignments. Amino-acid-selectively labeled NS4B can be readily obtained using cell-free synthesis, opening the door to combinatorial labeling approaches which should enable structural studies.     

Thermal conductance measurements of bolted copper to copper joints at sub-Kelvin temperatures

We have measured the thermal contact conductance of several demountable copper joints below 1 K. Joints were made by bolting together either two flat surfaces or a clamp around a rod. Surfaces were gold plated, and no intermediate materials were used. A linear dependence on temperature was seen. Most of the measured conductance values fell into a narrow range: 0.1-0.2 W K⁻¹ at 1 K. Results in the literature for similar joints consist of predictions based on electrical resistance measurements using the Wiedemann-Franz law. There is little evidence of the validity of this law in the case of joints. Nevertheless, our results are in good agreement with the literature predictions, suggesting that such predictions are a reasonable approximation.     

A machine learning system for identifying transmembrane domains from amino acid sequences

We present our machine learning system, that uses inductive logic programming techniques to learn how to identify transmembrane domains from amino acid sequences. Our system facilitates the use of operators such as ‘contains’, that act on entire sequences, rather than on individual elements of a sequence. The prediction accuracy of our new system is around 93%, and this compares favourably with earlier results. This work was carried out with the support of a research grant from ISIS, Fujitsu Laboratories.     

Operating experience from the ehecatl wind turbines

This paper presents a summary of the mechanical features and the medium term operating experience from three small horizontal axis wind energy conversion systems covering a range of 500 to 5000 Watt, intented for rural and isolated communities. These turbines have a new regulator which reduces gyroscopic loads, is easy to adjust and could be manufactured stronger and in smaller sizes than the conventional tail vanes. It is concluded that is feasible to build cheaps and reliable wind turbine generators with an acceptable efficiency employing common-use elements, but is needed a careful and optimized design.     

开关DC—DC变换器并联运行问题的研究

开关直流电源并联运行在许多场合应用。每一路电源输出阻抗的不一致性使每一路输出电流难以均衡，影响了系统的可靠性。本文提出了一种双回路ＤＣ—ＤＣ变换器的控制方案。由于采用电压环（外环）和电流环（内环）两环结构的双回路控制模式，变换器输出电流得到了有效控制，便于多个ＤＣ—ＤＣ变换器输出直接并联，从而实现了模块化，具有一定的实用性