Diabetic Cardiovascular Disease Induced by Oxidative Stress.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease

Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease

魚類におけるスクワレンおよびコレステロールの生合成 : I. アセテートのとり込みに関するin vitroの研究

アセテート-1-14Cからのスクワレンおよびコレステロールの生合成に関し,コイの肝膵臓,ニジマス肝臓およびマウス肝臓のホモジネート上澄液を用いて研究した.補酵素ATP,NAD,NADPおよびNADPHを添加し,30℃で好気的・嫌気的条件下に培養を行なった. アセテートの総脂質中へのとり込みは,ニジマス標品を用いた場合は非常に活潑で,コイ標品でもかなりな程度行なわれたが,マウス標品では著しく低い結果を得た.コイおよびニジマスで代表される魚類標品での脂肪酸合成はステロール合成を凌駕していたが,マウス標品では逆にコレステロール合成が優れていた. 一般的に魚類におけるコレステロール合成に関する補酵素要求性は陸上動物のそれとあまり相違してはいない. スクワレンからコレステロールへの閉環に関し要求される補助因子の一つとして,好気的条件下の合成にみられたように,分子状酸素が重要に作用する.さらに,深海産のサメ肝油中にみられる異常な程の大量なスクワレンとそれ程でもないコレステロールの含量に関して考察を加えた.The biosynthesis of squalene and cholesterol from acetate-1-14C has been studied in the homogenate supernatant of carp hepatopancreas, rainbow trout liver and mouse liver. The incubation was carried out with the addition of ATP, NAD, NADP and NADPH at 30℃ for certain periods of time under aerobic and anaerobic conditions. It was shown that the incorporation of acetate-l-14C into the total lipids was very active in the preparation of rainbow trout liver, less active in carp hepatopancreas, and low in mouse liver. In the fish preparation represented by carp and rainbow trout, the de novo synthesis of the fatty acids exceeds of the sterols. On the contrary, the cholesterogenesis surpasses the lipogenesis in the mouse liver preparation. In general, the coenzyme requirements for the cholesterol synthesis in the fish are not markedly different from those needed by land animals. As one of the cofactors required for the cyclization of squalene to lanosterol, the molecular oxygen is very important as shown in the case of aerobic condition. Moreover, it was discussed why certain deep sea sharks contain extraordinarily high amounts of squalene and little cholesterol in their liver oils.This work was partly supported by a grant from the Ministry of Education to the senior author (M.K., Title No. 86574)

Integrable Impurity Model with Spin and Flavour: Model Inspired by Resonant Tunneling in Quantum Dot

We introduce an integrable impurity model in which both electrons and impurity have spin and flavour degrees of freedom. This model is a generalization of the multi-channel Kondo model and closely related with resonant tunneling through quantum dot. The Hamiltonian is exactly diagonalized by means of the Bethe ansatz.Comment: 1 reference is adde

How is Learning Fluctuating? FutureLearn MOOCs Fine-Grained Temporal Analysis and Feedback to Teachers

Data-intensive analysis of massive open online courses (MOOCs) is popular. Researchers have been proposing various parameters conducive to analysis and prediction of student behaviour and outcomes in MOOCs, as well as different methods to analyse and use these parameters, ranging from statistics, to NLP, to ML, and even graph analysis. In this paper, we focus on patterns to be extracted, and apply systematic data analysis methods in one of the few genuinely large-scale data collection of 5 MOOCs, spread over 21 runs, on FutureLearn, a UK-based MOOCs provider, that, whilst offering a broad range of courses from many universities, NGOs and other institutions, has been less evaluated, in comparison to, e.g., its American counterparts. We analyse temporal quiz solving patterns; specifically, the less explored issue on how the first number of weeks of data predicts activities in the last weeks; we also address the classical MOOC question on the completion chance. Finally, we discuss the type of feedback a teacher or designer could receive on their MOOCs, in terms of fine-grained analysis of their material, and what personalisation could be provided to a student

Earliest Predictor of Dropout in MOOCs: A Longitudinal Study of FutureLearn courses

Whilst a high dropout rate is a well-known problem in MOOCs, few studies take a data-driven approach to understand the reasons of such a phenomenon, and to thus be in the position to recommend and design possible adaptive solutions to alleviate it. In this study, we are particularly interested in finding a novel early detection mechanism of potential dropout, and thus be able to intervene at an as early time as possible. Additionally, unlike previous studies, we explore a light-weight approach, based on as little data as possible – since different MOOCs store different data on their users – and thus strive to create a truly generalisable method. Therefore, we focus here specifically on the generally available registration date and its relation to the course start date, via a comprehensive, larger than average, longitudinal study of several runs of all MOOC courses at the University of Warwick between 2014-1017, on the less explored European FutureLearn platform. We identify specific periods where different interventions are necessary, and propose, based on statistically significant results, specific pseudo-rules for adaptive feedback

Ubiquitous organic molecule-based free-standing nanowires with ultra-high aspect ratios

ごくありふれた有機分子からナノ細線をつくり立たせて埋めつくす --立体電子回路や超高感度センサーへ--. 京都大学プレスリリース. 2021-06-30.The critical dimension of semiconductor devices is approaching the single-nm regime, and a variety of practical devices of this scale are targeted for production. Planar structures of nano-devices are still the center of fabrication techniques, which limit further integration of devices into a chip. Extension into 3D space is a promising strategy for future; however, the surface interaction in 3D nanospace make it hard to integrate nanostructures with ultrahigh aspect ratios. Here we report a unique technique using high-energy charged particles to produce free-standing 1D organic nanostructures with high aspect ratios over 100 and controlled number density. Along the straight trajectory of particles penetrating the films of various sublimable organic molecules, 1D nanowires were formed with approximately 10~15 nm thickness and controlled length. An all-dry process was developed to isolate the nanowires, and planar or coaxial heterojunction structures were built into the nanowires. Electrical and structural functions of the developed standing nanowire arrays were investigated, demonstrating the potential of the present ultrathin organic nanowire systems