bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Leaving No One Behind’: The Challenge of Reaching Migrant Populations
Authors: Laverack Glenn
Published: September 2018

The aim of this paper is to discuss the relevance of tailored interventions to ensure that vulnerable groups, such as migrants, are covered by public health programs. Most migrants do not have access to universal health care, including preventive and protective services. Tailored interventions can play an important role in helping to promote better migrant health through improved access to health care, increased awareness, better community-based structures and positive behaviour changes. The paper identifies some of the most effective strategies for the application of tailored public health interventions for migrants. In particular, migrants are especially vulnerable during a health emergency or disease outbreak and tailored approaches can be more effective than mainstream approaches. The paper advocates for the use of tailored interventions alongside the strengthening of universal health care to improve the health of migrants.
Big-Data-Mining-Based Improved K-Means Algorithm for Energy Use Analysis of Coal-Fired Power Plant Units: A Case Study
Authors: Liu Binghan , Fu Zhongguang , Wang Pengkai , Liu Lu , Gao Manda , Liu Ji
Published: September 2018

The energy use analysis of coal-fired power plant units is of significance for energy conservation and consumption reduction. One of the most serious problems attributed to Chinese coal-fired power plants is coal waste. Several units in one plant may experience a practical rated output situation at the same time, which may increase the coal consumption of the power plant. Here, we propose a new hybrid methodology for plant-level load optimization to minimize coal consumption for coal-fired power plants. The proposed methodology includes two parts. One part determines the reference value of the controllable operating parameters of net coal consumption under typical load conditions, based on an improved K-means algorithm and the Hadoop platform. The other part utilizes a support vector machine to determine the sensitivity coefficients of various operating parameters for the net coal consumption under different load conditions. Additionally, the fuzzy rough set attribute reduction method was employed to obtain the minimalist properties reduction method parameters to reduce the complexity of the dataset. This work is based on continuously-measured information system data from a 600 MW coal-fired power plant in China. The results show that the proposed strategy achieves high energy conservation performance. Taking the 600 MW load optimization value as an example, the optimized power supply coal consumption is 307.95 g/(kW·h) compared to the actual operating value of 313.45 g/(kW·h). It is important for coal-fired power plants to reduce their coal consumption.
Comment on “Glass Transition, Crystallization of Glass-Forming Melts, and Entropy” Entropy 2018, 20, 103.
Authors: Zanotto Edgar D. , Mauro John C.
Published: September 2018

In a recent article, Schmelzer and Tropin [Entropy 2018, 20, 103] presented a critique of several aspects of modern glass science, including various features of glass transition and relaxation, crystallization, and the definition of glass itself. We argue that these criticisms are at odds with well-accepted knowledge in the field from both theory and experiments. The objective of this short comment is to clarify several of these issues.
Robustness of Cyber-Physical Systems against Simultaneous, Sequential and Composite Attack
Authors: Cui Pengshuai , Zhu Peidong , Xun Peng , Shao Chengcheng
Published: September 2018

In this paper, a failure model of Cyber-Physical systems and an attack model are proposed. We divide the attacks into three kinds: simultaneous attack, sequential attack and composite attack. Through numerical simulations, we find that: (1) the sequential attack may bring more damage in single physical systems; (2) the coupling process of cyber system and physical systems makes it possible that sequential attack causes more damage than simultaneous attacks when the attackers only attack the cyber system; (3) with some target sets, composite attack leads to more failures than both simultaneous attack and sequential attack. The above results suggest that defenders should take all the three kinds of attacks into account when they select the critical nodes.
General Analysis of Switching Modes in a Dual Active Bridge with Triple Phase Shift Modulation
Authors: Calderon Carlos , Barrado Andres , Rodriguez Alba , Alou Pedro , Lazaro Antonio , Fernandez Cristina , Zumel Pablo
Published: September 2018

This paper provides an exhaustive analysis of the Dual-Active-Bridge with Triple-Phase-Shift (DAB-TPS) modulation and other simpler ones, identifying all the possible switching modes to operate the DAB in both power flow directions, and for any input-to-output voltage range and output power. This study shows four cases and seven switching modes for each case when the energy flows in one direction. That means that the DAB operates up to fifty-six different switching modes when the energy flows in both directions. Analytical expressions for the inductor current, the output power, and the boundaries between switching modes are provided for all cases. Additionally, the combination of control variables to achieve Zero-Voltage-Switching (ZVS) or Zero-Current-Switching (ZCS) is provided for each case and switching mode, by showing which switching modes obtain ZVS or ZCS for the whole power range and all switches—independent of the input-to-output voltage ratio. Therefore, the most interesting cases, switching mode and modulation for using the DAB are identified. Additionally, experimental validation has been carried out with a 250 W prototype. This analysis is a proper tool to design the DAB in the optimum switching mode, reducing the RMS current and achieving to increase efficiency and the power density.
Evaluation of the Vertical Producing Degree of Commingled Production via Waterflooding for Multilayer Offshore Heavy Oil Reservoirs
Authors: Shen Fei , Cheng Linsong , Sun Qiang , Huang Shijun
Published: September 2018

Recently, commingling production has been widely used for the development of offshore heavy oil reservoirs with multilayers. However, the differences between layers in terms of reservoir physical properties, oil properties and pressure have always resulted in interlayer interference, which makes it more difficult to evaluate the producing degree of commingled production. Based on the Buckley–Leverett theory, this paper presents two theoretical models, a one-dimensional linear flow model and a planar radial flow model, for water-flooded multilayer reservoirs. Through the models, this paper establishes a dynamic method to evaluate seepage resistance, sweep efficiency and recovery percent and then conducts an analysis with field data. The result indicates the following: (1) the dynamic difference in seepage resistance is an important form of interlayer interference during the commingled production of an offshore multilayer reservoir; (2) the difference between commingled production and separated production is small within a certain range of permeability ratio or viscosity ratio, but separated production should be adopted when the ratio exceeds a certain value.
Transmission Expansion Planning under Uncertainty for Investment Options with Various Lead-Times
Authors: Kim Wook-Won , Park Jong-Keun , Yoon Yong-Tae , Kim Mun-Kyeom
Published: September 2018

Investment options of transmission expansion planning (TEP) involve different lead times according to their length, technology, and environmental and social impacts. TEP planners can utilize the various lead times to deal with the risk of uncertainty. This paper proposes a novel framework for TEP under an uncertain environment, which includes investment options with various lead times. A multi-stage model is developed to reflect the different lead times in the planning method. The level of demand uncertainty is represented using a relative standard deviation. Demand uncertainty in the presented multi-stage model and its influence on the optimal decision are studied. The problem is formulated as a mixed integer linear problem to which stochastic programming is applied, and the proposed framework is illustrated from case studies on a modified Garver’s six-bus system. The case studies verify the effectiveness of the framework for TEP problems with a mathematically tractable model and demonstrates that the proposed method achieves better performance than other methods when the problems involve investment candidates with various lead times under uncertain conditions.
Fine-Root Responses of Populus tomentosa Forests to Stand Density
Authors: Bo Huijuan , Wen Chunyan , Song Lianjun , Yue Yatao , Nie Lishui
Published: September 2018

Stand density directly affects the distribution of ecological factors such as light, heat, and water in forest communities and changes the diversity and structure of undergrowth species, thereby affecting soil health. Fine roots can provide water and nutrients to plants rapidly in the fierce competition of soil resources, so as to get rid of environmental factors. This study examined the fine-root responses of the Populus tomentosa clone S86 to three stand densities (plant × row spacing: 2 × 2 m, 4 × 3 m, 4 × 5 m). We measured the biomass, morphology, and nitrogen content of lower- (1–3 order) and higher-order (>3 order) fine roots, and analyzed soil chemical properties in 10–30 cm. The soil from the density (2 × 2 m) stands showed lower soil organic matter content, available nitrogen, available phosphorous, and available potassium than others. Obviously, lower and higher-order fine roots were different: biomass of the >3 order accounted for 77–87% of the total biomass, 1–3-order fine-root diameter around 0.28–0.38 mm, while >3-order fine root were 1.28–1.69 mm; the length of 1–3-order fine root was longer than the >3 order, and root length density, specific root length, and nutrient content between the 1–3 and >3 orders were different. At 2 × 2 m, 1–3-order fine-root biomass was the highest, 132.5 g/m3, and the 1–3-order fine-root length, diameter, surface, root length density was also the highest; at the same time, the 1–3-order fine-root total nitrogen and organic matter content was also the highest, while the >3 order was highest under 4 × 3 m or 4 × 5 m. The findings of this study show that stand density affected the available nutrient content of the soil. When soil resources were poor, the biomass, morphology, and chemical content of fine roots were adjusted to increase the nutrient absorption rate, particularly in the lower-order roots.
Distribution Changes of Phosphorus in Soil–Plant Systems of Larch Plantations across the Chronosequence
Authors: Zeng Fanpeng , Chen Xin , Huang Bin , Chi Guangyu
Published: September 2018

Phosphorus (P) is one of the most important factors influencing the growth and quality of larch plantations. A systematic knowledge of the dynamic changes of P in soil–plant systems can provide a theoretical basis for the sustainable development of larch plantations. We determined the concentration, biomass, and accumulation of P in five tree components (i.e., leaf, branch, bark, stem, and root), and the concentrations of various soil P fractions of larch plantations in 10-, 25-, and 50-year-old stands in northeast China. Our results showed that the N:P ratio and P concentration in leaves increased with stand age, indicating that the growth of larch plantations might be limited by P in the development of stands. The N:P ratio and P concentration in roots, and P resorption efficiency, increased with stand age, indicating the use efficiency of P could be enhanced in older stands. The concentrations of soil-labile P fractions (Resin-P, NaHCO3-Pi, and NaHCO3-Po) in 25- and 50-year-old stands were significantly lower than those in 10-year-old stands, indicating the availability of soil P decreases with the development of larch plantations.
Drought-Affected Populus simonii Carr. Show Lower Growth and Long-Term Increases in Intrinsic Water-Use Efficiency Prior to Tree Mortality
Authors: Sun Shoujia , Qiu Lanfen , He Chunxia , Li Chunyou , Zhang Jinsong , Meng Ping
Published: September 2018

The Three-North Shelter Forest (TNSF) is a critical ecological barrier against sandstorms in northern China, but has shown extensive decline and death in Populus simonii Carr. in the last decade. We investigated the characteristics—tree-ring width, basal area increment (BAI), carbon isotope signature (13Ccor), and intrinsic water-use efficiency (iWUE)—of now-dead, dieback, and non-dieback trees in TNSF shelterbelts of Zhangbei County. Results from the three groups were compared to understand the long-term process of preceding drought-induced death and to identify potential early-warning proxies of drought-triggered damage. The diameter at breast height (DBH) was found to decrease with the severity of dieback, showing an inverse relationship. In all three groups, both tree-ring width and BAI showed quadratic relationships with age, and peaks earlier in the now-dead and dieback groups than in the non-dieback group. The tree-ring width and BAI became significantly lower in the now-dead and dieback groups than in the non-dieback group from 17 to 26 years before death, thus, these parameters can serve as early-warning signals for future drought-induced death. The now-dead and dieback groups had significantly higher δ13Ccor and iWUEs than the non-dieback group at 7–16 years prior to the mortality, indicating a more conservative water-use strategy under drought stress compared with non-dieback trees, possibly at the cost of canopy defoliation and long-term shoot dieback. The iWUE became significantly higher in the now-dead group than in the dieback group at 0–7 years before death, about 10 years later than the divergence of BAI. After the iWUE became significantly different among the groups, the now-dead trees showed lower growth and died over the next few years. This indicates that, for the TNSF shelterbelts studied, an abrupt iWUE increase can be used as a warning signal for acceleration of impending drought-induced tree death. In general, we found that long-term drought decreased growth and increased iWUE of poplar tree. Successive droughts could drive dieback and now-dead trees to their physiological limits of drought tolerance, potentially leading to decline and mortality episodes.
“Seeing What’s Left”: The Effect of Position of Transparent Windows on Product Evaluation
Authors: Simmonds Gregory , Woods Andy , Spence Charles
Published: September 2018

The position of design elements on product packaging has been shown to exert a measurable impact on consumer perception across a number of different studies and product categories. Design elements previously found to influence the consumer through their positioning on the front of pack include product imagery, brand logos, text-based claims, and basic shapes. However, as yet, no empirical research has focused specifically on the relative position of transparent windows; despite the latter being an increasingly prevalent element of many modern packaging designs. This exploratory online study details an experimental investigation of how manipulating the position of a transparent window on a range of visually-presented, novel packaging designs influences consumer evaluations and judgements of the product seen within. Specifically, 110 participants rated 24 different packaging designs (across four product categories: granola, boxed chocolates, pasta, and lemon mousse; each with six window positions: in one of the four quadrants, the top half, or the bottom half) in a within-participants experimental design. Analyses were conducted using Friedman’s tests and Hochberg procedure-adjusted Wilcoxon Signed-Rank Tests. Window position was found to be a non-trivial element of design, with a general preference for windows on the right-hand side being evidenced. Significantly higher scores for expected product tastiness and design attractiveness were consistently identified across all product categories when windows were positioned on the right- vs. left-hand side of the packaging. Effects on the perception of powerfulness, overall liking, quality, and willingness to purchase were identified, but were inconsistent across the different product categories. Very few effects of window verticality were identified, with expected weight of the product not being significantly influenced by window position. The implications of these findings for academics, designers, and brand managers are discussed, with future research directions highlighted.
How a Communication Intervention in Zambia Re-Oriented Health Services to the Needs of the Least-Supported
Authors: Klouda Tony , Green Cathy , Soyoola Miniratu , Quigley Paula , Kureya Tendayi , Barber Caroline , Mubuyaeta Kenneth
Published: September 2018

Despite decades of training health workers in communication, complaints from clients and communities about poor health worker attitudes abound. This was found to be so in Zambia where the More Mobilizing Access to Maternal Health Services in Zambia (MORE MAMaZ) program was trying to ensure the inclusion of under-supported women in a community-based maternal and newborn health program in five intervention districts. Under-supported women suffer a disproportionate burden of child mortality and are poor users of health services. An exploratory small-scale qualitative survey involving nurses from training schools and health facilities found that nurses knew how to communicate well, but were selective with whom and in what circumstances they did this. In general, those who received the worst communication were under-supported and had low confidence—the very people who needed the best communication. An experiential training program was started to help health workers reflect on the reasons for their poor communication. The training was evaluated after 14 months using semi-structured interviews and focus group discussions with staff at participating health facilities. The results showed improved inclusion of under-supported women but also increased attendance generally for ante-natal clinics, deliveries and under-five clinics. Another outcome was improved communication between, and a sense of job satisfaction among, the health workers themselves. The program demonstrated an effective way to improve the inclusion and involvement of the least-supported women and girls. There are important lessons for other health programs that aim to operationalize the goals of the Global Strategy for Women’s, Children’s and Adolescent’s Health, which include an emphasis on reaching every woman.
Use of Radiocarbon Ages to Narrow Groundwater Recharge Estimates in the Southeastern Mojave Desert, USA
Authors: Love Adam H. , Zdon Andy
Published: September 2018

Estimating groundwater recharge in arid or semiarid regions can be a difficult and complex task, since it is dependent on a highly variable set of spatial and temporal hydrologic parameters and processes that are dependent on the local climate, the land surface properties, and subsurface characteristics. As a result, traditional methods for estimating the recharge can result in a wide range of derived values. This is evident in the southeastern Mojave Desert, where calculated recharge estimates by previous investigators that range over an order of magnitude (from ~2500 to ~37,000 acre feet per year) are reported. To narrow down this large span of recharge estimates to narrower and more plausible values, this study evaluates the previous recharge estimates in this region, to examine the sources of variability in the reported results and to constrain the recharge estimates based on the hydrologic conditions and the radiocarbon age-dating of spring flows—even without knowledge of the precise subsurface hydrology. The groundwater age and perennial flow characteristics of springs in this study could not be derived from waters sourced solely from local recharge. Therefore, the springs in this study require a significant groundwater contribution to their overall discharge. A previously described conceptual site model in the region established that Bonanza Spring is similarly hydrologically connected to the regional basin-fill aquifer, based on geologic and geochemical/isotopic analyses, and this conceptual site model for where perennial spring water is sourced should readily be extended to these other perennial springs in this region.
Growth and Development of Children with Microcephaly Associated with Congenital Zika Virus Syndrome in Brazil
Authors: França Thaís Lorena Barbosa de , Medeiros Wilton Rodrigues , Souza Nilba Lima de , Longo Egmar , Pereira Silvana Alves , França Thamyris Barbosa de Oliveira , Sousa Klayton Galante
Published: September 2018

The outbreak of Zika virus in Latin America in the period 2015–2016 has caused a sudden increase in the number of severe manifestations and reports of congenital changes in newborns in Brazil. This is the first study that evaluated and compared the growth and cognitive and motor development of children with microcephaly due to Congenital Zika Virus Syndrome (CZS) in relation to typical children. It was an observational, analytical, cross-sectional study with 8 children with CZS and 16 typical children, with a mean age of 20.5 months (±2.1), in a region of northeastern Brazil. Considering the mean, children with CZS presented extremely low performance in the motor domain and in the cognitive development domain, whereas typical children presented average performance in the cognitive and motor development domains. Children with CZS presented a mean growth rate (head circumference and weight) lower than typical children. Therefore, children with CZS are at risk for growth retardation and development compared to typical children.
Associations of Physical Activity and Sedentary Time in Primary School Children with Their Parental Behaviors and Supports
Authors: Tanaka Chiaki , Okuda Masayuki , Tanaka Maki , Inoue Shigeru , Tanaka Shigeho
Published: September 2018

Background: The associations of objectively evaluated moderate-to-vigorous physical activity (MVPA) and sedentary time between primary school children and their fathers or mothers have not been fully understood. Therefore, we tested the associations in children. Methods: The participants were first to sixth grade boys (n = 166, 9.4 ± 1.6 years) and girls (n = 202, 9.4 ± 1.6 years) and their parents (fathers, n = 123 and mothers, n = 321). MVPA and sedentary time were measured using triaxial accelerometry. The relationship between parental support which was assessed by self-reported questionnaire and children’s MVPA was also examined. Results: MVPA in the children was positively correlated with maternal MVPA after adjustment for the children’s gender, grade, body mass index z-score, paternal or maternal age, and school (p < 0.001). However, paternal or maternal sedentary time and paternal MVPA showed no significant association with sedentary time or MVPA in children. On the other hand, the percentage of MVPA in children who spent more time with their mothers on weekends was significantly lower than those who spent less time (p = 0.034). Children whose mothers watched their sports events had a significantly higher percentage of MVPA than those whose mothers did not watch these events (p = 0.008). There were no associations between children’s MVPA and paternal support. Conclusions: The findings of this study demonstrate the significance of maternal MVPA and support.
Determinants of Health Care-Seeking Delay among Tuberculosis Patients in Rural Area of Central China
Authors: Tong Yeqing , Guan Xuhua , Hou Shuangyi , Cai Li , Huang Yadong , Wang Lei , Zhan Faxian , Shi Yuqin , Liu Jiafa
Published: September 2018

Background The prevalence of tuberculosis (TB) in low and middle-income countries is a significant public health and social concern. TB is a common infectious disease caused by the Mycobacterium tuberculosis infection, which has a widespread infection rate. Health care-seeking delay maybe one of the most important neglected risk factors for the spread of TB. Objectives The aim of this study was to understand the situation of health care-seeking delay among rural tuberculosis patients in Hubei Province, and explore its risk factors. Methods A total of 1408 rural tuberculosis patients were surveyed using a standard structured questionnaire in three cities of Hubei Province during the past two years. Results For the 1408cases of pulmonary tuberculosis, 39.70% of them were health care-seeking delayed. Logistic regressions indicate that the Han nationality, farming careers, the over 45 min walk to the township’s hospital, and awareness of the national TB free treatment policy, were significantly associated with higher odds of a delay in care seeking. Conclusions The prevalence of health care-seeking delay among tuberculosis patients was high in rural areas. It is essential to take comprehensive targeted interventions to reduce care-seeking delay.
Inequities in Childhood Vaccination Coverage in Zhejiang, Province: Evidence from a Decomposition Analysis on Two-Round Surveys
Authors: Hu Yu , Liang Hui , Wang Ying , Chen Yaping
Published: September 2018

Objective: The objectives of this study were to determine the degree and risk factors of the inequity in the childhood coverage of full primary immunization (FPI) in Zhejiang province. Method: We used data from two rounds of vaccination coverage surveys among children aged 24–35 months conducted in 2014 and 2017, respectively. The household income per month was used as an index of socioeconomic status for the inequality analysis. The concentration index (CI) was used to quantify the degree of inequality, and the decomposition approach was applied to quantify the contributions from demographic factors to inequality in the coverage of FPI. Results: The coverage rates of FPI were 80.6%, with a CI value of 0.12028 for the 2014 survey, while the coverage rates of FPI were 85.2%, with a CI value of 0.10129 for the 2017 survey. The results of decomposition analysis suggested that 68.2% and 67.1% of the socioeconomic inequality in the coverage of FPI could be explained by the mother’s education level for the 2014 and 2017 survey, respectively. Other risk factors including birth order, ethnic group, mother’s age, maternal employment status, residence, immigration status, GDP per-capita, and the percentage of the total health spending allocated to public health could also explain this inequality. Conclusion: The socioeconomic inequity in the coverage of FPI still remained, although this gap was reduced between 2014 and 2017. Policy recommendations for health interventions on reducing the inequality in the coverage of FPI should be focused on eliminating poverty and women’s illiteracy.
Wearable Monitoring Devices for Biomechanical Risk Assessment at Work: Current Status and Future Challenges—A Systematic Review
Authors: Ranavolo Alberto , Draicchio Francesco , Varrecchia Tiwana , Silvetti Alessio , Iavicoli Sergio
Published: September 2018

Background: In order to reduce the risk of work-related musculoskeletal disorders (WMSDs) several methods have been developed, accepted by the international literature and used in the workplace. The purpose of this systematic review was to describe recent implementations of wearable sensors for quantitative instrumental-based biomechanical risk assessments in prevention of WMSDs. Methods: Articles written until 7 May 2018 were selected from PubMed, Scopus, Google Scholar and Web of Science using specific keywords. Results: Instrumental approaches based on inertial measurement units and sEMG sensors have been used for direct evaluations to classify lifting tasks into low and high risk categories. Wearable sensors have also been used for direct instrumental evaluations in handling of low loads at high frequency activities by using the local myoelectric manifestation of muscle fatigue estimation. In the field of the rating of standard methods, on-body wireless sensors network-based approaches for real-time ergonomic assessment in industrial manufacturing have been proposed. Conclusions: Few studies foresee the use of wearable technologies for biomechanical risk assessment although the requirement to obtain increasingly quantitative evaluations, the recent miniaturization process and the need to follow a constantly evolving manual handling scenario is prompting their use.
Correction: Brázda, V. and Coufal, J. Recognition of Local DNA Structures by p53 Protein. Int. J. Mol. Sci. 2017, 18, 375
Authors: Brázda Václav , Coufal Jan
Published: September 2018

The authors wish to make the following corrections to their paper [1] [...]
Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway
Authors: Kim Sang-A , Kang Ok-Hwa , Kwon Dong-Yeul
Published: September 2018

Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3β pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug.
A New Synthetic Histone Deacetylase Inhibitor, MHY2256, Induces Apoptosis and Autophagy Cell Death in Endometrial Cancer Cells via p53 Acetylation
Authors: De Umasankar , Son Ji Yeon , Sachan Richa , Park Yu Jin , Kang Dongwan , Yoon Kyungsil , Lee Byung Mu , Kim In Su , Moon Hyung Ryong , Kim Hyung Sik
Published: September 2018

We previously discovered a novel sirtuin (SIRT) inhibitor, MHY2256, that exerts anticancer activity through p53 acetylation in MCF-7 human breast cancer cells. We investigated the anticancer activity of MHY2256 against hormone-related cancer, an endometrial cancer with a poor prognosis. The IC50 values of MHY2256 were shown to be much lower than those of salermide, a well-known SIRT inhibitor. Furthermore, MHY2256 significantly reduced the protein expression and activities of SIRT1, 2, and 3, with similar effects to salermide. Particularly, MHY2256 markedly inhibited tumor growth in a tumor xenograft mouse model of Ishikawa cancer cells. During the experimental period, there was no significant change in the body weight of mice treated with MHY2256. A detailed analysis of the sensitization mechanisms of Ishikawa cells revealed that late apoptosis was largely increased by MHY2256. Additionally, MHY2256 increased G1 arrest and reduced the number of cell cyclic-related proteins, suggesting that apoptosis by MHY2256 was achieved by cellular arrest. Particularly, p21 was greatly increased by MHY225656, suggesting that cell cycle arrest by p21 is a major factor in MHY2256 sensitization in Ishikawa cells. We also detected a significant increase in acetylated p53, a target protein of SIRT1, in Ishikawa cells after MHY2256 treatment. In a mouse xenograft model, MHY2256 significantly reduced tumor growth and weight without apparent side effects. These results suggest that MHY2256 exerts its anticancer activity through p53 acetylation in endometrial cancer and can be used for targeting hormone-related cancers.
Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study
Authors: Zhang Cheng , Wang Ning , Xu Yu , Tan Hor-Yue , Li Sha , Feng Yibin
Published: September 2018

Oxidative stress, defined as a disequilibrium between pro-oxidants and antioxidants, can result in histopathological lesions with a broad spectrum, ranging from asymptomatic hepatitis to hepatocellular carcinoma in an orchestrated manner. Although cells are equipped with sophisticated strategies to maintain the redox biology under normal conditions, the abundance of redox-sensitive xenobiotics, such as medicinal ingredients originated from herbs or animals, can dramatically invoke oxidative stress. Growing evidence has documented that the hepatotoxicity can be triggered by traditional Chinese medicine (TCM) during treating various diseases. Meanwhile, TCM-dependent hepatic disorder represents a strong correlation with oxidative stress, especially the persistent accumulation of intracellular reactive oxygen species. Of note, since TCM-derived compounds with their modulated targets are greatly diversified among themselves, it is complicated to elaborate the potential pathological mechanism. In this regard, data mining approaches, including network pharmacology and bioinformatics enrichment analysis have been utilized to scientifically disclose the underlying pathogenesis. Herein, top 10 principal TCM-modulated targets for oxidative hepatotoxicity including superoxide dismutases (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), glutathione peroxidase (GPx), Bax, caspase-3, Bcl-2, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nitric oxide (NO) have been identified. Furthermore, hepatic metabolic dysregulation may be the predominant pathological mechanism involved in TCM-induced hepatotoxic impairment.
The Beneficial Effect of Proanthocyanidins and Icariin on Biochemical Markers of Bone Turnover in Rats
Authors: Oršolić Nada , Nemrava Johann , Jeleč Željko , Kukolj Marina , Odeh Dyana , Terzić Svjetlana , Fureš Rajko , Bagatin Tomica , Bagatin Dinko
Published: September 2018

Nutrition is an important factor that influences bone metabolism, the endocrine and/or paracrine system, and bone-active mineral elements homeostasis. We studied antiosteoporotic effects of grape seed proanthocyanidins extract, icariin or alendronate (ALN) in retinoic acid-induced (13cRA) bone loss in rats. Proanthocyanidins and icariin have beneficial effects on bone health; they have improved the bone weight reduction, the length and the diameter of the bone, calcium, and phosphorus content in bone ash, bone mineral density (BMD), the biochemical markers of bone turnover and uterus atrophy induced by 13cRA. All results suggest that proanthocyanidins and icariin reverse osteoporosis in 13cRA rats by stimulating bone formation or regulating bone resorption by their antioxidative and estrogenic-like activity without toxic side-effects observed in ALN treatment.
Whole Body Vibration Therapy after Ischemia Reduces Brain Damage in Reproductively Senescent Female Rats
Authors: Raval Ami P. , Schatz Marc , Bhattacharya Pallab , D’Adesky Nathan , Rundek Tatjana , Dietrich W. Dalton , Bramlett Helen M.
Published: September 2018

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV improves cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and were randomly assigned to either WBV or no-WBV groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of the treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the no-WBV group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.
Hyperglycemia-Associated Dysregulation of O-GlcNAcylation and HIF1A Reduces Anticancer Action of Metformin in Ovarian Cancer Cells (SKOV-3)
Authors: Rogalska Aneta , Forma Ewa , Bryś Magdalena , Śliwińska Agnieszka , Marczak Agnieszka
Published: September 2018

Although cancer cells need more glucose than normal cells to maintain energy demand, chronic hyperglycemia induces metabolic alteration that may dysregulate signaling pathways, including the O-GlcNAcylation and HIF1A (Hypoxia-inducible factor 1-alpha) pathways. Metformin was demonstrated to evoke metabolic stress and induce cancer cell death. The aim of this study was to determine the cytotoxic efficiency of metformin on SKOV-3 cells cultured in hyperglycemia and normoglycemia. To identify the potential mechanism, we assessed the expression of O-linked β-N-acetlyglucosamine transferase (OGT) and glycoside hydrolase O-GlcNAcase (OGA), as well as hypoxia-inducible factor 1-alpha (HIF1A) and glucose transporters (GLUT1, GLUT3). SKOV-3 cells were cultured in normoglycaemia (NG, 5 mM) and hyperglycemia (HG, 25 mM) with and without 10 mM metformin for 24, 48, and 72 h. The proliferation rate, apoptotic and necrotic SKOV-3 cell death were evaluated. Real-Time qPCR was employed to determine mRNA expression of OGT, OGA, GLUT1, GLUT3, and HIF1A. Metformin significantly reduced the proliferation of SKOV-3 cells under normal glucose conditions. Whereas, the efficacy of metformin to induce SKOV-3 cell death was reduced in hyperglycemia. Both hyperglycemia and metformin induced changes in the expression of genes involved in the O-GlcNAcylation status and HIF1A pathway. The obtained results suggest that dysregulation of O-GlcNAcylation, and the related HIF1A pathway, via hyperglycemia, is responsible for the decreased cytotoxic efficiency of metformin in human ovarian cancer cells.
Protective Actions of Anserine Under Diabetic Conditions
Authors: Peters Verena , Calabrese Vittorio , Forsberg Elisabete , Volk Nadine , Fleming Thomas , Baelde Hans , Weigand Tim , Thiel Christian , Trovato Angela , Scuto Maria , Modafferi Sergio , Schmitt Claus
Published: September 2018

Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Methods: Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Results: Anserine has a higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20–100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05). Conclusion: Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy.
Ascorbic Acid in Colon Cancer: From the Basic to the Clinical Applications
Authors: El Halabi Ibrahim , Bejjany Rachelle , Nasr Rihab , Mukherji Deborah , Temraz Sally , Nassar Farah J. , El Darsa Haidar , Shamseddine Ali
Published: September 2018

Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. Based on these findings, we conclude that further clinical trials are needed on a larger scale to examine the therapeutic benefits of AA in colon cancer.
Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation
Authors: Zippel Nina , Loot Annemarieke E. , Stingl Heike , Randriamboavonjy Voahanginirina , Fleming Ingrid , Fisslthaler Beate
Published: September 2018

AMP-activated protein kinase (AMPK) is frequently reported to phosphorylate Ser1177 of the endothelial nitric-oxide synthase (eNOS), and therefore, is linked with a relaxing effect. However, previous studies failed to consistently demonstrate a major role for AMPK on eNOS-dependent relaxation. As AMPK also phosphorylates eNOS on the inhibitory Thr495 site, this study aimed to determine the role of AMPKα1 and α2 subunits in the regulation of NO-mediated vascular relaxation. Vascular reactivity to phenylephrine and acetylcholine was assessed in aortic and carotid artery segments from mice with global (AMPKα−/−) or endothelial-specific deletion (AMPKαΔEC) of the AMPKα subunits. In control and AMPKα1-depleted human umbilical vein endothelial cells, eNOS phosphorylation on Ser1177 and Thr495 was assessed after AMPK activation with thiopental or ionomycin. Global deletion of the AMPKα1 or α2 subunit in mice did not affect vascular reactivity. The endothelial-specific deletion of the AMPKα1 subunit attenuated phenylephrine-mediated contraction in an eNOS- and endothelium-dependent manner. In in vitro studies, activation of AMPK did not alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation on Thr495. Depletion of AMPKα1 in cultured human endothelial cells decreased Thr495 phosphorylation without affecting Ser1177 phosphorylation. The results of this study indicate that AMPKα1 targets the inhibitory phosphorylation Thr495 site in the calmodulin-binding domain of eNOS to attenuate basal NO production and phenylephrine-induced vasoconstriction.
An Integrated Graph Model for Document Summarization
Authors: Yang Kang , Al-Sabahi Kamal , Xiang Yanmin , Zhang Zuping
Published: September 2018

Extractive summarization aims to produce a concise version of a document by extracting information-rich sentences from the original texts. The graph-based model is an effective and efficient approach to rank sentences since it is simple and easy to use. However, its performance depends heavily on good text representation. In this paper, an integrated graph model (iGraph) for extractive text summarization is proposed. An enhanced embedding model is used to detect the inherent semantic properties at the word level, bigram level and trigram level. Words with part-of-speech (POS) tags, bigrams and trigrams were extracted to train the embedding models. Based on the enhanced embedding vectors, the similarity values between the sentences were calculated in three perspectives. The sentences in the document were treated as vertexes and the similarity between them as edges. As a result, three different types of semantic graphs were obtained for every document, with the same nodes and different edges. These three graphs were integrated into one enriched semantic graph in a naive Bayesian fashion. After that, TextRank, which is a graph-based ranking algorithm, was applied to rank the sentences, before the top scored sentences were selected for the summary according to the compression rate. Evaluated on the DUC 2002 and DUC 2004 datasets, our proposed method shows competitive performance compared to the state-of-the-art methods.
Spotted Wing Drosophila in Sweet Cherry Orchards in Relation to Forest Characteristics, Bycatch, and Resource Availability
Authors: Hennig Ernest Ireneusz , Mazzi Dominique
Published: September 2018

Forest vegetation is essential for the population development of the spotted wing drosophila (SWD). Yet, little is known of how the structure of surrounding forest areas influence the abundance of SWD within orchards. In this work, we use data from a field trial at five sites in Switzerland to analyse the relationship between the extent of forest area, its edge density, and its distance from the orchard with the occurrence of SWD in sweet cherry orchards in a Bayesian hierarchical model. Availability of cherries and bycatch were also included in the model to account for effects of resource availability and trap attractiveness, respectively. For all main effects and their interactions, we accounted for potential temporal changes by adding interactions with time. We found that the closer an orchard was to a forest, the more SWD were trapped within the orchard. However, the interaction of forest proximity with forest area caused a disproportionate decrease of SWD catches. Also, the within orchard variables, trap catches of other drosophilid flies and resource availability affected SWD trap catches, but their relation changed in the course of the experiment. The findings imply that reducing SWD occurrence in orchards and other crop fields requires not only the consideration of processes outside and within the host crop field, but also of temporally changing relationships between SWD and other factors.