bluuebunny/crossref_metadata_2025 huggingface dataset:
Proton Exchange Membrane Fuel Cell Stack Design Optimization Using an Improved Jaya Algorithm
Authors: Chakraborty Uday K.
Published: August 2019

Fuel cell stack configuration optimization is known to be a problem that, in addition to presenting engineering challenges, is computationally hard. This paper presents an improved computational heuristic for solving the problem. The problem addressed in this paper is one of constrained optimization, where the goal is to seek optimal (or near-optimal) values of (i) the number of proton exchange membrane fuel cells (PEMFCs) to be connected in series to form a group, (ii) the number of such groups to be connected in parallel, and (iii) the cell area, such that the PEMFC assembly delivers the rated voltage at the rated power while the cost of building the assembly is as low as possible. Simulation results show that the proposed method outperforms four of the best-known methods in the literature. The improvement in performance afforded by the proposed algorithm is validated with statistical tests of significance.
Impact of Longitudinal Acceleration and Deceleration on Bluff Body Wakes
Authors: Peters Brett , Uddin Mesbah
Published: August 2019

This study investigated the unsteady acceleration aerodynamics of bluff bodies through the study of a channel mounted square cylinder undergoing free-stream acceleration of ±20 ms−2 with Reynolds numbers spanning 3.2 × 104 to 3.6 × 105. To achieve this, a numerical simulation was created with a commercial finite volume unstructured computational fluid dynamics code, which was first validated using Improved Delayed Detached Eddy Simulation against experimental and direct numerical simulated results. Then, the free stream conditions were subjected to a periodic velocity signal where data were recorded and ensemble averaged over at least 30 distinct acceleration and deceleration data points. This enabled the comparison of body forces and flow field variations among accelerating, steady and decelerating free-stream conditions. Body force analysis determined that decelerating and accelerating drag forces varied −47% and 44%, respectively, in comparison to steady free-stream conditions. In addition, several differences were also observed and explored such as near-body flow structures, wake dynamics, Kármán vortices and vorticity production during the aforementioned conditions. The primary interest of this study was for the future application towards road vehicles for predictive dynamic modeling and aerodynamic development.
The “Grass-Fed” Milk Story: Understanding the Impact of Pasture Feeding on the Composition and Quality of Bovine Milk
Authors: Alothman Mohammad , Hogan Sean A. , Hennessy Deirdre , Dillon Pat , Kilcawley Kieran N. , O’Donovan Michael , Tobin John , Fenelon Mark A. , O’Callaghan Tom F.
Published: August 2019

Milk is a highly nutritious food that contains an array of macro and micro components, scientifically proven to be beneficial to human health. While the composition of milk is influenced by a variety of factors, such as genetics, health, lactation stage etc., the animal’s diet remains a key mechanism by which its nutrition and processing characteristics can be altered. Pasture feeding has been demonstrated to have a positive impact on the nutrient profile of milk, increasing the content of some beneficial nutrients such as Omega-3 polyunsaturated fatty acids, vaccenic acid, and conjugated linoleic acid (CLA), while reducing the levels of Omega-6 fatty acids and palmitic acid. These resultant alterations to the nutritional profile of “Grass-Fed” milk resonate with consumers that desire healthy, “natural”, and sustainable dairy products. This review provides a comprehensive comparison of the impact that pasture and non-pasture feeding systems have on bovine milk composition from a nutritional and functional (processability) perspective, highlighting factors that will be of interest to dairy farmers, processors, and consumers.
PKS 2155-304: A Case Study of Blazar Variability Power Spectrum at the Highest Energies and on the Longest Timescales
Authors: Goyal Arti
Published: August 2019

We present the results of our Power Spectral Density (PSD) analysis for the BL Lac object PKS 2155-304, utilizing the nightly-binned long-term light curve from the decade-long monitoring, as well as the minute-binned intra-night light curve from the High Energy Stereoscopic Survey (H.E.S.S.; >200 GeV). The source is unique for exhibiting the shortest flux-doubling timescale at Very High Energy (VHE) among its class and thus provides a rare opportunity to study the particle acceleration on the smallest spatial scales in blazar jets. The light curves are modeled in terms of the Continuous-Time Auto-Regressive Moving Average (CARMA) process. The combined long-term and intra-night PSD extends up to ∼6 decades in the temporal frequency range; unprecedented at the TeV energies for a blazar source. Our systematic approach reveals that PKS 2155-304 shows, on average, a complex shape of variability power spectrum, with more variability power on longer timescales. The long-term variability is best modeled by the CARMA(2,1) process, while the intra-night variability is modeled by a CARMA(1,0) process. We note that the CARMA(1,0) process refers to an Ornstein–Uhlenbeck process where the power-law PSD slope (PSD varies as a function of variability frequency to the power of the negative slope) changes from two to zero, above a certain “characteristic/relaxation” timescale. Even though the derived power spectrum of the intra-night light curve did not reveal a flattening, we speculate such relaxation must occur on timescales longer than a few hours for the source.
Mobile Self-Monitoring ECG Devices to Diagnose Arrhythmia that Coincide with Palpitations: A Scoping Review
Authors: Marston Hannah Ramsden , Hadley Robin , Banks Duncan , Duro María Del Carmen Miranda
Published: August 2019

The use and deployment of mobile devices across society is phenomenal with an increasing number of individuals using mobile devices to track their everyday health. However, there is a paucity of academic material examining this recent trend. Specifically, little is known about the use and deployment of mobile heart monitoring devices for measuring palpitations and arrhythmia. In this scoping literature review, we identify the contemporary evidence that reports the use of mobile heart monitoring to assess palpitations and arrhythmia across populations. The review was conducted between February and March 2018. Five electronic databases were searched: Association for Computing Machinery (ACM), CINHAL, Google Scholar, PubMed, and Scopus. A total of 981 records were identified and, following the inclusion and exclusion criteria, nine papers formed the final stage of the review. The results identified a total of six primary themes: purpose, environment, population, wearable devices, assessment, and study design. A further 24 secondary themes were identified across the primary themes. These included detection, cost effectiveness, recruitment, type of setting, type of assessment, and commercial or purpose-built mobile device. This scoping review highlights that further work is required to understand the impact of mobile heart monitoring devices on how arrhythmias and palpitations are assessed and measured across all populations and ages of society. A positive trend revealed by this review demonstrates how mobile heart monitoring devices can support primary care providers to deliver high levels of care at a low cost to the service provider. This has several benefits: alleviation of patient anxiety, lowering the risk of morbidity and mortality, while progressively influencing national and international care pathway guidelines. Limitations of this work include the paucity of knowledge and insight from primary care providers and lack of qualitative material. We argue that future studies consider qualitative and mixed methods approaches to complement quantitative methodologies and to ensure all actors’ experiences are recorded.
Associations between Self-Determined Motivation, Accelerometer-Determined Physical Activity, and Quality of Life in Chinese College Students
Authors: Tao Kun , Liu Wenxi , Xiong Shanying , Ken Lodewyk , Zeng Nan , Peng Qingwen , Yan Xiaoni , Wang Junli , Wu Yizhong , Lei Mingzhi , Li Xianxiong , Gao Zan
Published: August 2019

Purpose: To better promote college students’ physical activity (PA) and quality of life (QoL), it is imperative to understand this population’s PA correlates, such as self-determined motivation and perceived competence. However, few studies existed in this area of inquiry among Chinese college students. Thus, the purpose of this study was to examine the relationships among Chinese college students’ self-determined motivation, PA, and QoL. Method: A total of 220 college students (115 females; Mage = 20.29 years, SD = 2.37; MBMI = 20.67) were recruited from one university in south-central China. Participants were instructed to wear the ActiGraph GT9X Link (ActiGraph, Pensacola, FL, USA) accelerometers for 7 days. A minute-by-minute stepping rate methodology was used to determine participants sedentary behaviors, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Participants’ self-determined motivation (autonomous, controlled, and amotivation), perceived competence, and QoL (physical function, stress, depression, fatigue, sleep, and social issues) were assessed by a battery of validated surveys in June 2017. Results: Participants reported moderate–high levels of PA correlates and QoL as the means ranged from 5.5 to 6 (out of 7) for PA correlates and 2.75 to 4 (out of 4) for QoL. The minute-by-minute stepping rate revealed participants had average 580.51 min/day in sedentary, 134.77 min/day in LPA, and 1.57 min/day in MVPA. Regression analyses for physical function, stress, depression, and social issues suggested that the models explained 4%–8% of the variances. Specifically, perceived competence was the negative predictor of the problems with physical function (β = −0.17, p < 0.05) and depression (β = −0.18, p < 0.01), amotivation was positively associated with depression and stress (p < 0.05). Additionally, controlled motivation predicted the ability to participate in social roles and activities (β = 0.22, p < 0.05). No significant predictors emerged for fatigue or for sleep. Conclusions: Findings suggest Chinese college students’ perceived competence and social support are critical for improving PA and QoL. In addition, strategies are needed to motivate Chinese college students to engage in PA participation and improve overall well-being.
Elderly Health Inequality in China and its Determinants: A Geographical Perspective
Authors: Fan Chenjing , Ouyang Wei , Tian Li , Song Yan , Miao Wensheng
Published: August 2019

Inter-regional health differences and apparent inequalities in China have recently received significant attention. By collecting health status data and individual socio-economic information from the 2015 fourth sampling survey of the elderly population in China (4th SSEP), this paper uses the geographical differentiation index to reveal the spatial differentiation of health inequality among Chinese provinces. We test the determinants of inequalities by multilevel regression models at the provincial and individual levels, and find three main conclusions: 1) There were significant health differences on an inter-provincial level. For example, provinces with a very good or good health rating formed a good health hot-spot region in the Yangtze River Delta, versus elderly people living in Gansu and Hainan provinces, who had a poor health status. 2) Nearly 2.4% of the health differences in the elderly population were caused by inter-provincial inequalities; access (or lack of access) to economic, medical and educational resources was the main reason for health inequalities. 3) At the individual level, inequalities in annual income served to deepen elderly health differences, and elderly living in less developed areas were more vulnerable to urban vs. rural-related health inequalities.
The Effect of Plyometric Training in Volleyball Players: A Systematic Review
Authors: Silva Ana Filipa , Clemente Filipe Manuel , Lima Ricardo , Nikolaidis Pantelis T. , Rosemann Thomas , Knechtle Beat
Published: August 2019

Volleyball is considered a very explosive and fast-paced sport in which plyometric training is widely used. Our purpose was to review the effects of plyometric training on volleyball players’ performance. A systematic search was conducted according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using PubMed, SciELO, SPORTDiscus, Medline, Scopus, Academic Search Complete, CINAHL and Web Science for articles published no later than December 2018. Any criteria were imposed for the included sample. The search focus was on interventional studies in which athletes underwent a plyometric program. To the 1831 articles found, another five were added, identified through other sources. Duplicated files were removed, titles and abstracts were screened, which left 21 remaining studies for extensive analysis. Results showed that the vertical jump (15 studies) was the major ability studied in plyometric training interventions, followed by strength (four studies), horizontal jump (four studies), flexibility (four studies) and agility/speed (three studies). In addition, it was observed that young (under 18 years old) female athletes were the most studied. The included studies indicated that plyometric training seems to increase vertical jump performance, strength, horizontal jump performance, flexibility and agility/speed in volleyball players. However, more studies are needed to better understand the benefits of plyometric training in volleyball players’ performance.
Development of a Computational Model to Predict Excess Body Fat in Adolescents through Low Cost Variables
Authors: Sousa Carlos Magno , Santana Ewaldo , Lopes Marcus Vinicius , Lima Guilherme , Azoubel Luana , Carneiro Érika , Barros Allan Kardec , Pires Nilviane
Published: August 2019

Background: Excess body fat has been growing alarmingly among adolescents, especially in low income and middle income countries where access to health services is scarce. Currently, the main method for assessing overweight in adolescents is the body mass index, but its use is criticized for its low sensitivity and high specificity, which may lead to a late diagnosis of comorbidities associated with excess body fat, such as cardiovascular diseases. Thus, the aim of this study was to develop a computational model using linear regression to predict obesity in adolescents and compare it with commonly used anthropometric methods. To improve the performance of our model, we estimated the percentage of fat and then classified the nutritional status of these adolescents. Methods: The model was developed using easily measurable socio-demographic and clinical variables from a database of 772 adolescents of both genders, aged 10–19 years. The predictive performance was evaluated by the following metrics: accuracy, sensitivity, specificity, and area under ROC curve. The performance of the method was compared to the anthropometric parameters: body mass index and waist-to-height ratio. Results: Our model showed a high correlation (R = 0.80) with the body fat percentage value obtained through bioimpedance. In addition, regarding discrimination, our model obtained better results compared to BMI and WHtR: AUROC = 0.80, 0.64, and 0.55, respectively. It also presented a high sensitivity of 92% and low false negative rate (6%), while BMI and WHtR showed low sensitivity (27% and 9.9%) and a high false negative rate (65% and 53%), respectively. Conclusions: The computational model of this study obtained a better performance in the evaluation of excess body fat in adolescents, compared to the usual anthropometric indicators presenting itself as a low cost alternative for screening obesity in adolescents living in Brazilian regions where financial resources are scarce.
Breaking Through Barriers and Building Disaster Mental Resilience: A Case Study in the Aftermath of the 2015 Nepal Earthquakes
Authors: KC Alisha , Gan Connie Cai Ru , Dwirahmadi Febi
Published: August 2019

Introduction: Nepal was hit by two devastating earthquakes in 2015 that disrupted its socio-economic system and shattered many lives, resulting in increased mental health issues during the post-earthquake phase. Disasters can have severe mental health impacts on the affected population, making it necessary to enhance resilience within communities and to help them to adapt well in the face of adversities. From these earthquakes, this study looks to identify measures needed to develop community mental resilience for disaster preparedness in Nepal. Method: We conducted this research using the qualitative case study method and thematic analysis (TA). Result: Several activities were carried out by organizations to support the psycho-social aspects of communities, but were challenged by existing barriers. After considering the present context, this study presents five recommendations for mental resilience and also suggests the utilization of existing resources, such as faith-based organizations and teachers in the communities. Despite the considerable impact, communities demonstrate their own resilience, to some extent, through the culture of sharing and helping each other. Conclusions: A firm commitment is required from the government to enhance resilience by mainstreaming mental health in all areas of disaster management and planning.
Health-Related Participatory Research in American Indian and Alaska Native Communities: A Scoping Review
Authors: Woodbury R. Brian , Ketchum Scott , Hiratsuka Vanessa Y. , Spicer Paul
Published: August 2019

A scoping review was conducted to assess the state of the literature on health-related participatory research involving American Indian and Alaska Native communities. Online databases were searched for relevant articles published between 1/1/2000 and 5/31/2017. 10,000+ data points relevant to community-level engagement in and regulation of research, community research capacity and cultural adaptation were extracted from 178 articles. Community engagement varied across study components: 136 (76%) articles reported community participation in research-related meetings and other events and 49 (27%) articles reported community involvement in initiation of research. 156 (88%) articles reported use of community-level tools to guide or regulate research. 93 (52%) articles reported that community members received research-related training. 147 (82%) articles described some type of cultural adaptation. Across all articles, data points on community engagement were not reported in 3061 (40%) out of 7740 cases. Findings suggest a need for increased community engagement in early stages of the research process and for reporting guidelines for participatory research involving American Indian and Alaska Native communities. There is also need to further existing research on the impact of different components of participatory research on process and outcome measures and to develop funding mechanisms that account for the time and resource intensive nature of participatory research.
Exosomal L1CAM Stimulates Glioblastoma Cell Motility, Proliferation, and Invasiveness
Authors: Pace Karma R. , Dutt Reetika , Galileo Deni S.
Published: August 2019

Immunoglobulin superfamily protein L1CAM (L1, CD171) normally facilitates neuronal migration, differentiation, and axon guidance during development. Many types of cancers, including glioblastoma (GBM), also abnormally express L1, and this has been associated with poor prognosis due to increased cell proliferation, invasiveness, or metastasis. We showed previously that the soluble L1 ectodomain, which is proteolyzed from the transmembrane form, can stimulate proliferation and motility of GBM cells in vitro by acting through integrins and fibroblast growth factor receptors (FGFRs). Minute L1-decorated exosomal vesicles also are released by GBM cells and potentially could stimulate cell motility, proliferation, and invasiveness, but this needed to be demonstrated. In the present study, we aimed to determine if minute L1-decorated extracellular vesicles (exosomes) were capable of stimulating GBM cell motility, proliferation, and invasiveness. L1-decorated exosomes were isolated from the conditioned media of the human T98G GBM cell line and were evaluated for their effects on the behavior of glioma cell lines and primary tumor cells. L1-decorated exosomes significantly increased cell velocity in the three human glioma cells tested (T98G/shL1, U-118 MG, and primary GBM cells) in a highly quantitative SuperScratch assay compared to L1-reduced exosomes from L1-attenuated T98G/shL1 cells. They also caused a marked increase in cell proliferation as determined by DNA cell cycle analysis and cell counting. In addition, L1-decorated exosomes facilitated initial GBM cell invasion when mixed with non-invasive T98G/shL1 cells in our chick embryo brain tumor model, whereas mixing with L1-reduced exosomes did not. Chemical inhibitors against focal adhesion kinase (FAK) and fibroblast growth factor receptor (FGFR) decreased L1-mediated motility and proliferation to varying degrees. These novel data show that L1-decoratred exosomes stimulate motility, proliferation and invasion to influence GBM cell behavior, which adds to the complexity of how L1 stimulates cancer cells through not only soluble ectodomain but also through exosomes.
Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease
Authors: Fontes Adriana , Alemany-Pagès Mireia , Oliveira Paulo J. , Ramalho-Santos João , Zischka Hans , Azul Anabela Marisa
Published: August 2019

Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria.
Durum Wheat Stress Tolerance Induced by Endophyte Pantoea agglomerans with Genes Contributing to Plant Functions and Secondary Metabolite Arsenal
Authors: Cherif-Silini Hafsa , Thissera Bathini , Bouket Ali Chenari , Saadaoui Nora , Silini Allaoua , Eshelli Manal , Alenezi Faizah N. , Vallat Armelle , Luptakova Lenka , Yahiaoui Bilal , Cherrad Semcheddine , Vacher Sebastien , Rateb Mostafa E. , Belbahri Lassaad
Published: August 2019

In the arid region Bou-Saâda at the South of Algeria, durum wheat Triticum durum L. cv Waha production is severely threatened by abiotic stresses, mainly drought and salinity. Plant growth-promoting rhizobacteria (PGPR) hold promising prospects towards sustainable and environmentally-friendly agriculture. Using habitat-adapted symbiosis strategy, the PGPR Pantoea agglomerans strain Pa was recovered from wheat roots sampled in Bou-Saâda, conferred alleviation of salt stress in durum wheat plants and allowed considerable growth in this unhostile environment. Strain Pa showed growth up to 35 °C temperature, 5–10 pH range, and up to 30% polyethylene glycol (PEG), as well as 1 M salt concentration tolerance. Pa strain displayed pertinent plant growth promotion (PGP) features (direct and indirect) such as hormone auxin biosynthesis, production of 1-aminocyclopropane-1-carboxylate (ACC) deaminase, and ammonia and phosphate solubilization. PGPR features were stable over wide salt concentrations (0–400 mM). Pa strain was also able to survive in seeds, in the non-sterile and sterile wheat rhizosphere, and was shown to have an endophytic life style. Phylogenomic analysis of strain Pa indicated that Pantoea genus suffers taxonomic imprecision which blurs species delimitation and may have impacted their practical use as biofertilizers. When applied to plants, strain Pa promoted considerable growth of wheat seedlings, high chlorophyll content, lower accumulation of proline, and favored K+ accumulation in the inoculated plants when compared to Na+ in control non-inoculated plants. Metabolomic profiling of strain Pa under one strain many compounds (OSMAC) conditions revealed a wide diversity of secondary metabolites (SM) with interesting salt stress alleviation and PGP activities. All these findings strongly promote the implementation of Pantoea agglomerans strain Pa as an efficient biofertilizer in wheat plants culture in arid and salinity-impacted regions.
Cytoplasmic Inter-Subunit Interface Controls Use-Dependence of Thermal Activation of TRPV3 Channel
Authors: Macikova Lucie , Vyklicka Lenka , Barvik Ivan , Sobolevsky Alexander I. , Vlachova Viktorie
Published: August 2019

The vanilloid transient receptor potential channel TRPV3 is a putative molecular thermosensor widely considered to be involved in cutaneous sensation, skin homeostasis, nociception, and pruritus. Repeated stimulation of TRPV3 by high temperatures above 50 °C progressively increases its responses and shifts the activation threshold to physiological temperatures. This use-dependence does not occur in the related heat-sensitive TRPV1 channel in which responses decrease, and the activation threshold is retained above 40 °C during activations. By combining structure-based mutagenesis, electrophysiology, and molecular modeling, we showed that chimeric replacement of the residues from the TRPV3 cytoplasmic inter-subunit interface (N251–E257) with the homologous residues of TRPV1 resulted in channels that, similarly to TRPV1, exhibited a lowered thermal threshold, were sensitized, and failed to close completely after intense stimulation. Crosslinking of this interface by the engineered disulfide bridge between substituted cysteines F259C and V385C (or, to a lesser extent, Y382C) locked the channel in an open state. On the other hand, mutation of a single residue within this region (E736) resulted in heat resistant channels. We propose that alterations in the cytoplasmic inter-subunit interface produce shifts in the channel gating equilibrium and that this domain is critical for the use-dependence of the heat sensitivity of TRPV3.
Discovery of Novel TASK-3 Channel Blockers Using a Pharmacophore-Based Virtual Screening
Authors: Ramírez David , Concha Guierdy , Arévalo Bárbara , Prent-Peñaloza Luis , Zúñiga Leandro , Kiper Aytug K. , Rinné Susanne , Reyes-Parada Miguel , Decher Niels , González Wendy , Caballero Julio
Published: August 2019

TASK-3 is a two-pore domain potassium (K2P) channel highly expressed in the hippocampus, cerebellum, and cortex. TASK-3 has been identified as an oncogenic potassium channel and it is overexpressed in different cancer types. For this reason, the development of new TASK-3 blockers could influence the pharmacological treatment of cancer and several neurological conditions. In the present work, we searched for novel TASK-3 blockers by using a virtual screening protocol that includes pharmacophore modeling, molecular docking, and free energy calculations. With this protocol, 19 potential TASK-3 blockers were identified. These molecules were tested in TASK-3 using patch clamp, and one blocker (DR16) was identified with an IC50 = 56.8 ± 3.9 μM. Using DR16 as a scaffold, we designed DR16.1, a novel TASK-3 inhibitor, with an IC50 = 14.2 ± 3.4 μM. Our finding takes on greater relevance considering that not many inhibitory TASK-3 modulators have been reported in the scientific literature until today. These two novel TASK-3 channel inhibitors (DR16 and DR16.1) are the first compounds found using a pharmacophore-based virtual screening and rational drug design protocol.
Dynamic Changes in Metabolite Accumulation and the Transcriptome during Leaf Growth and Development in Eucommia ulmoides
Authors: Li Long , Liu Minhao , Shi Kan , Yu Zhijing , Zhou Ying , Fan Ruishen , Shi Qianqian
Published: August 2019

Eucommia ulmoides Oliver is widely distributed in China. This species has been used mainly in medicine due to the high concentration of chlorogenic acid (CGA), flavonoids, lignans, and other compounds in the leaves and barks. However, the categories of metabolites, dynamic changes in metabolite accumulation and overall molecular mechanisms involved in metabolite biosynthesis during E. ulmoides leaf growth and development remain unknown. Here, a total of 515 analytes, including 127 flavonoids, 46 organic acids, 44 amino acid derivatives, 9 phenolamides, and 16 vitamins, were identified from four E. ulmoides samples using ultraperformance liquid chromatography–mass spectrometry (UPLC-MS) (for widely targeted metabolites). The accumulation of most flavonoids peaked in growing leaves, followed by old leaves. UPLC-MS analysis indicated that CGA accumulation increased steadily to a high concentration during leaf growth and development, and rutin showed a high accumulation level in leaf buds and growing leaves. Based on single-molecule long-read sequencing technology, 69,020 transcripts and 2880 novel loci were identified in E. ulmoides. Expression analysis indicated that isoforms in the flavonoid biosynthetic pathway and flavonoid metabolic pathway were highly expressed in growing leaves and old leaves. Co-expression network analysis suggested a potential direct link between the flavonoid and phenylpropanoid biosynthetic pathways via the regulation of transcription factors, including MYB (v-myb avian myeloblastosis viral oncogene homolog) and bHLH (basic/helix-loop-helix). Our study predicts dynamic metabolic models during leaf growth and development and will support further molecular biological studies of metabolite biosynthesis in E. ulmoides. In addition, our results significantly improve the annotation of the E. ulmoides genome.
A Concise Review on the Molecular Structure and Function Relationship of β-Glucan
Authors: Du Bin , Meenu Maninder , Liu Hongzhi , Xu Baojun
Published: August 2019

β-glucan is a non-starch soluble polysaccharide widely present in yeast, mushrooms, bacteria, algae, barley, and oat. β-Glucan is regarded as a functional food ingredient due to its various health benefits. The high molecular weight (Mw) and high viscosity of β-glucan are responsible for its hypocholesterolemic and hypoglycemic properties. Thus, β-glucan is also used in the food industry for the production of functional food products. The inherent gel-forming property and high viscosity of β-glucan lead to the production of low-fat foods with improved textural properties. Various studies have reported the relationship between the molecular structure of β-glucan and its functionality. The structural characteristics of β-glucan, including specific glycosidic linkages, monosaccharide compositions, Mw, and chain conformation, were reported to affect its physiochemical and biological properties. Researchers have also reported some chemical, physical, and enzymatic treatments can successfully alter the molecular structure and functionalities of β-glucan. This review article attempts to review the available literature on the relationship of the molecular structure of β-glucan with its functionalities, and future perspectives in this area.
Novel Insights into Regulation of Human Teeth Biomineralization: Deciphering the Role of Post-Translational Modifications in a Tooth Protein Extract
Authors: Sharma Vaibhav , Rani Komal , Roychoudhury Ajoy , Chawla Amita , Nikolajeff Fredrik , Kumar Saroj
Published: August 2019

The importance of whole protein extracts from different types of human teeth in modulating the process of teeth biomineralization is reported. There are two crucial features in protein molecules that result in efficient teeth biomineralization. Firstly, the unique secondary structure characteristics within these proteins i.e. the exclusive presence of a large amount of intrinsic disorder and secondly, the presence of post-translational modifications (PTM) like phosphorylation and glycosylation within these protein molecules. The present study accesses the structural implications of PTMs in the tooth proteins through scanning electron microscopy and transmission electron microscopy. The deglycosylated/dephosphorylated protein extracts failed to form higher-order mineralization assemblies. Furthermore, through nanoparticle tracking analysis (NTA) we have shown that dephosphorylation and deglycosylation significantly impact the biomineralization abilities of the protein extract and resulted in smaller sized clusters. Hence, we propose these post-translational modifications are indispensable for the process of teeth biomineralization. In addition to basic science, this study would be worth consideration while designing of biomimetics architecture for an efficient peptide-based teeth remineralization strategy.
Tetracycline Analogs Inhibit Osteoclast Differentiation by Suppressing MMP-9-Mediated Histone H3 Cleavage
Authors: Kim Yeojin , Kim Jinman , Lee Hyerim , Shin Woo-Ri , Lee Sheunghun , Lee Jisu , Park Jae-Il , Jhun Byung Hak , Kim Yang-Hoon , Yi Sun-Ju , Kim Kyunghwan
Published: August 2019

Osteoporosis is a common disorder of bone remodeling, caused by the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Recently, we reported that matrix metalloproteinase-9 (MMP-9)-dependent histone H3 proteolysis is a key event for proficient osteoclast formation. Although it has been reported that several MMP-9 inhibitors, such as tetracycline and its derivatives, show an inhibitory effect on osteoclastogenesis, the molecular mechanisms for this are not fully understood. Here we show that tetracycline analogs, especially tigecycline and minocycline, inhibit osteoclast formation by blocking MMP-9-mediated histone H3 tail cleavage. Our molecular docking approach found that tigecycline and minocycline are the most potent inhibitors of MMP-9. We also observed that both inhibitors significantly inhibited H3 tail cleavage by MMP-9 in vitro. These compounds inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by blocking the NFATc1 signaling pathway. Furthermore, MMP-9-mediated H3 tail cleavage during osteoclast differentiation was selectively blocked by these compounds. Treatment with both tigecycline and minocycline rescued the osteoporotic phenotype induced by prednisolone in a zebrafish osteoporosis model. Our findings demonstrate that the tetracycline analogs suppress osteoclastogenesis via MMP-9-mediated H3 tail cleavage, and suggest that MMP-9 inhibition could offer a new strategy for the treatment of glucocorticoid-induced osteoporosis.
Galectin-9 Is a Possible Promoter of Immunopathology in Rheumatoid Arthritis by Activation of Peptidyl Arginine Deiminase 4 (PAD-4) in Granulocytes
Authors: Wiersma Valerie R. , Clarke Alex , Pouwels Simon D. , Perry Elizabeth , Abdullah Trefa M. , Kelly Clive , Soyza Anthony De , Hutchinson David , Eggleton Paul , Bremer Edwin
Published: August 2019

The aetiology of rheumatoid arthritis (RA) is unknown, but citrullination of proteins is thought to be an initiating event. In addition, it is increasingly evident that the lung can be a potential site for the generation of autoimmune triggers before the development of joint disease. Here, we identified that serum levels of galectin-9 (Gal-9), a pleiotropic immunomodulatory protein, are elevated in RA patients, and are even further increased in patients with comorbid bronchiectasis, a lung disease caused by chronic inflammation. The serum concentrations of Gal-9 correlate with C-reactive protein levels and DAS-28 score. Gal-9 activated polymorphonuclear leukocytes (granulocytes) in vitro, which was characterized by increased cytokine secretion, migration, and survival. Further, granulocytes treated with Gal-9 upregulated expression of peptidyl arginine deiminase 4 (PAD-4), a key enzyme required for RA-associated citrullination of proteins. Correspondingly, treatment with Gal-9 triggered citrullination of intracellular granulocyte proteins that are known contributors to RA pathogenesis (i.e., myeloperoxidase, alpha-enolase, MMP-9, lactoferrin). In conclusion, this study identifies for the first time an immunomodulatory protein, Gal-9, that triggers activation of granulocytes leading to increased PAD-4 expression and generation of citrullinated autoantigens. This pathway may represent a potentially important mechanism for development of RA.
Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Is Reversed by SIRT1
Authors: Garten Antje , Grohmann Theresa , Kluckova Katarina , Lavery Gareth G. , Kiess Wieland , Penke Melanie
Published: August 2019

Sorafenib is a multi-kinase inhibitor and one of the few systemic treatment options for patients with advanced hepatocellular carcinomas (HCCs). Resistance to sorafenib develops frequently and could be mediated by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin (SIRT)1. We aimed to test whether sorafenib efficacy is influenced by cellular NAD levels and NAD-dependent SIRT1 function. We analyzed sorafenib effects on apoptosis induction, NAD salvage, mitochondrial function, and related signaling pathways in HCC cell lines (HepG2, Hep3B, und HUH7) overexpressing SIRT1 or supplemented with the NAD metabolite nicotinamide mononucleotide (NMN) compared to controls. Treatment of HCC cell lines with sorafenib dose-dependently induced apoptosis and a significant decrease in cellular NAD concentrations. The SIRT1 protein was downregulated in HUH7 cells but not in Hep3B cells. After sorafenib treatment, mitochondrial respiration in permeabilized cells was lower, citrate synthase activity was attenuated, and cellular adenosine triphosphate (ATP) levels were decreased. Concomitant to increased phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), sorafenib treatment led to decreased activity of the mechanistic target of rapamycin (mTOR), indicative of energy deprivation. Transient overexpression of SIRT1, as well as NAD repletion by NMN, decreased sorafenib-induced apoptosis. We can, therefore, conclude that sorafenib influences the NAD/SIRT1/AMPK axis. Overexpression of SIRT1 could be an underlying mechanism of resistance to sorafenib treatment in HCC.
A Casing Treatment with Axial Grooves for Centrifugal Compressors
Authors: Leichtfuß Sebastian , Bühler Johannes , Schiffer Heinz-Peter , Peters Patrick , Hanna Michael
Published: August 2019

This paper provides an investigation of a casing treatment (CT) approach for pressure ratio improvements of centrifugal compressors between peak efficiency and surge. Results were experimentally verified for a variety of automotive turbocharger compressors and analyzed with 3D CFD. The CT design is an adaptation from an axial high-pressure compressor, which was successfully applied and intensively investigated in recent years. The aerodynamic working principle of the applied CT design and the achievable improvements are shown and described. The demand of operating range for automotive applications typically dictates high inlet shroud to outlet radius ratio (high trim) and past experiences indicate that a recirculation zone is formed in the inducer for those centrifugal compressors. This recirculation at the inlet shroud causes losses, a massive blockage and induces a co-rotating swirl at the inlet of the impeller. The result is a reduced pressure ratio, often leading to flat speed lines between the onset of recirculation and surge. This paper provides an understanding of inducer recirculation, its impacts and suggests countermeasures. The CT design for centrifugal compressors only influences flow locally at the inducer and prevents recirculation. It differs substantially in design and functionality from the classical bleed slot system commonly used to increase operating range. An experimental and CFD comparison between these designs is presented. While the classical bleed slot system often provides a massive increase in operating range, it often fails to increase the pressure ratio between onset of inducer recirculation and surge. In contrast, the CT design achieves a gain in pressure ratio near surge.
Deep Reinforcement Learning Algorithms in Intelligent Infrastructure
Authors: Serrano Will
Published: August 2019

Intelligent infrastructure, including smart cities and intelligent buildings, must learn and adapt to the variable needs and requirements of users, owners and operators in order to be future proof and to provide a return on investment based on Operational Expenditure (OPEX) and Capital Expenditure (CAPEX). To address this challenge, this article presents a biological algorithm based on neural networks and deep reinforcement learning that enables infrastructure to be intelligent by making predictions about its different variables. In addition, the proposed method makes decisions based on real time data. Intelligent infrastructure must be able to proactively monitor, protect and repair itself: this includes independent components and assets working the same way any autonomous biological organisms would. Neurons of artificial neural networks are associated with a prediction or decision layer based on a deep reinforcement learning algorithm that takes into consideration all of its previous learning. The proposed method was validated against an intelligent infrastructure dataset with outstanding results: the intelligent infrastructure was able to learn, predict and adapt to its variables, and components could make relevant decisions autonomously, emulating a living biological organism in which data flow exhaustively.
Blast Loading Response of Reinforced Concrete Panels Externally Reinforced with Steel Strips
Authors: Khan Rizwan , Farooq Syed Hassan , Usman Muhammad
Published: August 2019

Frequent terrorist activities, the use of vehicle bomb blasts and improvised explosive devices (IEDs) have brought forth the task of protection against blasts as a priority issue for engineers. Terrorists mostly target the areas where human and economic losses are significantly higher. It is really challenging to study the effects of blast loading on structures due to numerous variables. For instance, the type of detonation charge, explosive material, placement of charge and standoff distance, etc., are a few of the variables which make the system more complicated. Reinforced cement concrete (RCC) wall panels are commonly used for protecting important installations and buildings. In this research, the response of RCC wall panels has been investigated due to the blast effect caused by two TNT charge weights of 50 kg and 100 kg. These two charge weights have been selected after a detailed study of terrorist activities in the recent past. For this purpose, an existing arrangement at an important military installation, i.e., NESCOM Hospital Islamabad in Pakistan, has been selected. To reduce computational efforts, three RCC wall panels, placed side by side producing a continuous front along with a corresponding boundary and structural wall, have been considered. RCC wall panels are placed at a distance of 3 ft from the perimeter of the boundary wall and 23 ft from the structural wall. The displacement on the front face of RCC wall panels and the structural wall is measured at three levels of top, middle and bottom. ANSYS AUTODYN software has been used to simulate the model. Analysis has been carried out to identify and study the weakness of existing arrangements. Literature was reviewed for suggesting an appropriate strengthening technique for existing structures against blast loading. It was found that in addition to existing strengthening techniques, use of steel strips is amongst the most feasible technique for strengthening existing structures. It not only significantly enhanced the blast performance of structures, but it also significantly reduced z-direction displacements and pressures. The results show that the use of steel strips as the improvement technique for already placed RCC wall panels can be effective against a blast loading of up to 100 kg TNT.
Human Acireductone Dioxygenase (HsARD), Cancer and Human Health: Black Hat, White Hat or Gray?
Authors: Liu Xinyue , Pochapsky Thomas C.
Published: August 2019

Multiple factors involving the methionine salvage pathway (MSP) and polyamine biosynthesis have been found to be involved in cancer cell proliferation, migration, invasion and metastasis. This review summarizes the relationships of the MSP enzyme acireductone dioxygenase (ARD), the ADI1 gene encoding ARD and other gene products (ADI1GP) with carcinomas and carcinogenesis. ARD exhibits structural and functional differences depending upon the metal bound in the active site. In the penultimate step of the MSP, the Fe2+ bound form of ARD catalyzes the on-pathway oxidation of acireductone leading to methionine, whereas Ni2+ bound ARD catalyzes an off-pathway reaction producing methylthiopropionate and carbon monoxide, a biological signaling molecule and anti-apoptotic. The relationship between ADI1GP, MSP and polyamine synthesis are discussed, along with possible role(s) of metal in modulating the cellular behavior of ADI1GP and its interactions with other cellular components.
Effect of Coordinating Solvents on the Structure of Cu(II)-4,4′-bipyridine Coordination Polymers
Authors: Rancan Marzio , Carlotto Alice , Bottaro Gregorio , Armelao Lidia
Published: August 2019

Solvent can play a crucial role in the synthesis of coordination polymers (CPs). Here, this study reports how the coordinating solvent approach (CSA) can be used as an effective tool to control the nature of the final CP. This study exploited the system Cu(II)-4,4′-bipyridine coupled to different coordinating solvents, such as DMA, DMF and DMSO. This allowed the isolation and structurally characterization of four new CPs: three 2D layered networks and one 1D chain. Moreover, it was evidenced that even adventitious water can play the role of the coordinating solvent in the final CP.