Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

Influencer-defaulter mutation-based optimization algorithms for predicting electricity prices

Efficient electricity price forecasting plays a significant role in our society. In this paper, a novel influencer-defaulter mutation (IDM) mutation operator has been proposed. The IDM operator has been combined with six well-known optimization algorithms to create mutated optimization algorithms whose performance has been tested on twenty-four standard benchmark functions. Further, the artificial neural network is integrated with mutated optimization algorithms to solve the electricity price prediction problem. The policymakers can identify appropriate variables based on the predicted prices to help future market planning. The statistical results prove the efficacy of the IDM operator on the recent optimization algorithms.     

电气化铁路既有线深路堑扩堑石方控制爆破

介绍电气化铁路既有线无隔墙台阶爆破扩堑方法。沿既有线方向设置低台阶 ,边界处布置光爆孔 ,采用“同列同段和列间微差”的起爆网路。采用自制的“炮被”和架设“钢管排架”阻挡飞石、滚石和滑石 ,确保了既有线的安全。文中还概述了“炮被”和“钢管排架”的制做以及作者的认识和体会。     

New Insights into the Pathogenesis of Systemic Mastocytosis

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management of SM is highly individualized and was largely palliative for patients without a targeted form of therapy in past decades. Targeted therapy with midostaurin, a multiple kinase inhibitor that inhibits KIT, has demonstrated efficacy in patients with advanced SM. This led to the recent approval of midostaurin by the United States Food and Drug Administration and European Medicines Agency. However, the overall survival of patients treated with midostaurin remains unsatisfactory. The identification of genetic and epigenetic alterations and understanding their interactions and the molecular mechanisms involved in mastocytosis is necessary to develop rationally targeted therapeutic strategies. This review briefly summarizes recent developments in the understanding of SM pathogenesis and potential treatment strategies for patients with SM.     

Visually deficient working conditions and reduced work performance in office workers: Is it mediated by visual discomfort?

IntroductionThe main purpose of this cross-sectional study was to investigate whether visual discomfort acts as a mediating factor between perceived visual ergonomic working conditions and self-rated visual performance among office workers who carry out administrative tasks and computer-based work at the Swedish Tax Agency.MethodsA questionnaire was sent to 94 office workers addressing: 1) perceived visual quality of the visual display units; 2) prevalence of eye symptoms; and 3) self-rated visual performance. Eighty-six persons (54 women (63%), 31 men (36%), and 1 of unspecified sex) answered the questionnaire. Multiple regression analysis investigated the association between visual ergonomic working conditions and visual performance, both with and without visual discomfort as a mediator.ResultsThe group mean of the Indexed survey questions indicated a reasonably good quality of visual ergonomic working conditions, a relative absence of eye symptoms, and acceptable self-rated visual performance. Results from multiple regression analysis showed a significant association between perceived visual ergonomic working conditions and self-rated visual performance (r² = 0.30, β = 0.327, p < 0.01). When visual discomfort was used as a mediator, the association between perceived visual ergonomic working conditions and self-rated visual performance remained the same (r² = 0.32, β = 0.315, p < 0.01).DiscussionIt was remarkable to discover that self-rated visual performance was independent of visual discomfort. Possible explanations include exposure factors not included in the current study, such as dry air and sensory irritation in the eyes, psychosocial stress, time spent performing near work activities, or time exposed to visually deficient working conditions.Relevance to industryThe strong connection between satisfaction with visual ergonomic working conditions and productivity in this study has implications for workplace profitability and staff satisfaction. If productivity is enhanced by better visual ergonomic working conditions, then managers of workplaces may be able to improve work outcomes by optimizing the physical work environment.     

基于时间延迟的多类型维修与经济生产批量联合优化研究

针对目前未能较好的综合考虑多维修类型与经济生产批量联合优化的问题，首先考虑多类型维修关系，基于时间延迟理论求出故障和缺陷次数的表达式；其次，在此基础上，综合考虑生产费用和维修费用的基础上，构建了多类型维修和经济生产批量联合优化模型，以单位时间内总费用最小为优化目标，获得最优检查间隔期和经济生产批量；最后，通过算例分析验证了模型的有效性，说明了第一类缺陷检查次数的多少对费用和经济生产批量影响不大。     

碳源对manA基因突变大肠杆菌代谢的影响

ManA基因编码的甘露糖-6-磷酸异构酶在大肠杆菌中催化D-甘露糖和D-果糖的异构化,促进大肠杆菌对碳源的代谢吸收。本文通过研究manA基因突变大肠杆菌对碳源的利用和编码糖代谢基因情况,探讨甘露糖-6-磷酸异构酶对大肠杆菌糖代谢的影响。采用Ⅱ型内含子逆转录突变方法构建manA基因突变大肠杆菌,分析manA基因突变大肠杆菌对不同碳源的利用情况和manA基因突变对大肠杆菌糖代谢相关基因表达的影响,结果显示,大肠杆菌BL21(DE3)ΔmanA以甘露糖、果糖为碳源时,菌株生长受到显著抑制;以淀粉为碳源时,BL21(DE3)ΔmanA菌株的生长显著优于野生型大肠杆菌;以葡萄糖为碳源时,manA基因突变对大肠杆菌的生长无显著影响。通过基因表达分析,发现大肠杆菌BL21(DE3)ΔmanA中甘露糖代谢相关基因的表达显著性降低;果糖代谢途径中6-磷酸果糖激酶Ⅰ亚基的编码基因(pfkA)显著下调表达;水解淀粉的α-淀粉酶编码基因(malS)显著性上调表达。ManA基因突变影响大肠杆菌甘露糖、果糖和淀粉代谢途径中相关基因的表达,从而影响大肠杆菌对碳源的利用。     

盖子环替换及定点突变提高菜豆环氧化物水解酶对邻甲基苯基缩水甘油醚的催化性能

菜豆环氧化物水解酶1和2（PvEH1、PvEH2）能够动力学拆分外消旋邻甲基苯基缩水甘油醚（rac-oMGE），从而保留(R)-oMGE。基于对PvEH1和PvEH2结构的同源模拟和分析，发现二者分子中的盖子环差异较大，故本文选择盖子环作为研究目标。经融合聚合酶链式反应（FPCR），获得了PvEH2的盖子环区域被PvEH1对应区域替换的杂合酶Pv2Pv1。用全细胞酶E. coli/pv2pv1催化rac-oMGE，当(S)-oMGE刚好水解完全时，产物(S)-3-邻甲苯基-1,2-丙二醇（(S)-oTPD）的ee_p由PvEH2的58.3%提高至75.5%。为进一步提高酶的性质，在Pv2Pv1中选取11个氨基酸位点进行丙氨酸(A)突变，获得最优突变子E. coli/pv2pv1^K176A，活性为E. coli/pv2pv1（4.2U/g）的2.1倍，且当S构型的底物刚好完全水解时，(S)-oTPD的ee_p进一步提高为80.3%。分子对接分析发现，盖子环替换和K176位点突变为A，均使(R)-oMGE环氧环中的C_α更易受到酶中D101位点的攻击。利用E. coli/pv2pv1^K176A催化150mmol/L rac-oMGE水解制备(R)-oMGE（ee_s＞99%）和(S)-oTPD（ee_p=80.4%），二者的产率Y_S和Y_P分别为32.7%和60.1%，时空产率STY_S和STY_P为1.6g/(L·h)和3.3g/(L·h)。本实验为改善EH的催化性质提供了一种有效策略。     

Improving basic relationships of pipe hydraulics

This communication presents the approaches set up for processing spinner flowmeter well logs in vertical wells with a single fluid phase, which is the most widely used in assessing wells productivity. These focus on improving the pipe hydraulics relationships so that the different fluid inputs throughout the well can be quantified. Since vertical flow inside wells varies with depth between laminar flows (very low Reynolds number, i.e. Re < 10³) and turbulent (Re > 4·10³) the aim has been to reduce the uncertainty in the transition interval. Starting from bibliographical data and/or well-known formulas for laminar and for turbulent flow, several continuous relationships have been developed for any regime: 1) an expression for the radial distribution of velocity inside the pipeline (velocity profile) was developed. 2) A relationship between the average velocity and the velocity at the axis (velocity factor) was created. 3) A third equation was generated to obtain the friction factor in smooth pipes (and starting from this, a new explicit equation for rough pipes). The purpose has been to have a set of empirical expressions of easy and continuous application for any regime, as an alternative to the use of computer simulations.     

An interval observer for uncertain continuous‐time linear systems

To design robust interval observers for uncertain continuous‐time linear systems, a new set‐integration approach is proposed to compute trajectory tubes for the estimation error. Because this approach, the order‐preserving condition on the dynamics of the estimation error is no longer required. Therefore, synthesis methods can be used to compute observer gains that reduce the impact of the system uncertainties on the accuracy of the estimated state enclosures. The performance of the proposed approach is showcased through illustrative numerical examples.