bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Optical Properties of Tapered Optical Fibers with Liquid Crystal Cladding Doped with Gold Nanoparticles
Authors: Moś Joanna E. , Korec Joanna , Stasiewicz Karol A. , Jankiewicz Bartłomiej , Bartosewicz Bartosz , Jaroszewicz Leszek R.
Published: June 2019

This paper presents results obtained for biconical tapered fibers surrounded/immersed in liquid crystal mixtures. The phenomenon of light propagating in the whole structure of a tapered fiber allows the creation of a sensor where the tapered region represents a core whereas the surrounding medium becomes a cladding. Created devices are very sensitive to changing refractive index value in a surrounding medium caused by modifying external environmental parameters like temperature, electric or magnetic field. For this reason, the properties of materials used as cladding should be easily modified. In this investigation, cells have been filled with two different nematic liquid crystals given as 1550* and 6CHBT (4-(trans-4-n-hexylcyclohexyl) isothiocyanatobenzoate), as well as with the same mixtures doped with 0.1 wt% gold nanoparticles (AuNPs). Optical spectrum analysis for the wavelength range of 550–1150 nm and time-courses performed for a wavelength of 846 nm at the temperature range of T = 25–40 °C were provided. For all investigations, a steering voltage in the range of 0–200 V which allows establishing the dopes’ influence on transmitted power and time response at different temperatures was applied.
A Suggestion of Converting Protein Intrinsic Disorder to Structural Entropy Using Shannon’s Information Theory
Authors: Guo Hao-Bo , Ma Yue , Tuskan Gerald , Qin Hong , Yang Xiaohan , Guo Hong
Published: June 2019

We propose a framework to convert the protein intrinsic disorder content to structural entropy (H) using Shannon’s information theory (IT). The structural capacity (C), which is the sum of H and structural information (I), is equal to the amino acid sequence length of the protein. The structural entropy of the residues expands a continuous spectrum, ranging from 0 (fully ordered) to 1 (fully disordered), consistent with Shannon’s IT, which scores the fully-determined state 0 and the fully-uncertain state 1. The intrinsically disordered proteins (IDPs) in a living cell may participate in maintaining the high-energy-low-entropy state. In addition, under this framework, the biological functions performed by proteins and associated with the order or disorder of their 3D structures could be explained in terms of information-gains or entropy-losses, or the reverse processes.
MHD Casson Fluid Flow over a Stretching Sheet with Entropy Generation Analysis and Hall Influence
Authors: Abd El-Aziz Mohamed , Afify Ahmed A.
Published: June 2019

The impacts of entropy generation and Hall current on MHD Casson fluid over a stretching surface with velocity slip factor have been numerically analyzed. Numerical work for the governing equations is established by using a shooting method with a fourth-order Runge–Kutta integration scheme. The outcomes show that the entropy generation is enhanced with a magnetic parameter, Reynolds number and group parameter. Further, the reverse behavior is observed with the Hall parameter, Eckert number, Casson parameter and slip factor. Also, it is viewed that Bejan number reduces with a group parameter.
Gearbox Fault Diagnosis Based on Hierarchical Instantaneous Energy Density Dispersion Entropy and Dynamic Time Warping
Authors: Tang Guiji , Pang Bin , He Yuling , Tian Tian
Published: June 2019

The accurate fault diagnosis of gearboxes is of great significance for ensuring safe and efficient operation of rotating machinery. This paper develops a novel fault diagnosis method based on hierarchical instantaneous energy density dispersion entropy (HIEDDE) and dynamic time warping (DTW). Specifically, the instantaneous energy density (IED) analysis based on singular spectrum decomposition (SSD) and Hilbert transform (HT) is first applied to the vibration signal of gearbox to acquire the IED signal, which is designed to reinforce the fault feature of the signal. Then, the hierarchical dispersion entropy (HDE) algorithm developed in this paper is used to quantify the complexity of the IED signal to obtain the HIEDDE as fault features. Finally, the DTW algorithm is employed to recognize the fault types automatically. The validity of the two parts that make up the HIEDDE algorithm, i.e., the IED analysis for fault features enhancement and the HDE algorithm for quantifying the information of signals, is numerically verified. The proposed method recognizes the fault patterns of the experimental data of gearbox accurately and exhibits advantages over the existing methods such as multi-scale dispersion entropy (MDE) and refined composite MDE (RCMDE).
Recruitment and Retention of International School Teachers in Remote Archipelagic Countries: The Fiji Experience
Authors: Dos Santos Luis Miguel
Published: June 2019

In current school environments, teacher recruitment, turnover, and retention present significant problems, particularly for rural and remote international schools in archipelagic countries. Employing the Social Cognitive Career Theory (SCCT), this study analyzed international school teachers with teaching experience at a Fijian international school about their career development, retention ideas, and the decision of teaching service. As there is not a large population of international school teachers in archipelagic countries due to the unique environment of the school and country, the researcher employed the Interpretative Phenomenological Analysis (IPA) to better understand six international school teachers who have taught and are teaching at one of the Fijian international schools. The study categorized two directions for leaving and staying at a remote location. Participants indicated that the managerial styles, negative leadership, and limited social networking were the most significant challenges while respectfulness and simple living style were the most significant advantages of their Fijian teaching experience. As this study mainly focused on the issues for rural, remote, and archipelagic countries, the result of this study serves as one of the first blueprints for organizational leaders in those regions to improve their management styles in order to recruit and retain their skillful professionals.
Wind Power Economic Feasibility under Uncertainty and the Application of ANN in Sensitivity Analysis
Authors: Rotela Junior Paulo , Fischetti Eugenio , Araújo Victor G. , Peruchi Rogério S. , Aquila Giancarlo , Rocha Luiz Célio S. , Lacerda Liviam S.
Published: June 2019

Wind power has grown popular in past recent years due to environmental issues and the search for alternative energy sources. Thus, the viability for wind power generation projects must be studied in order to attend to the environmental concerns and still be attractive and profitable. Therefore, this article aims to perform a sensitive analysis in order to identify the variables that influence most in the viability of a wind power investment for small size companies in the Brazilian northeast. For this, a stochastic analysis of viability through Monte Carlo Simulation (MCS) will be made and afterwards, Artificial Neural Networks (ANN) models will be applied for the most relevant variables identification. Through the sensitivity, it appears that the most relevant factors in the analysis are the speed of wind, energy tariff and the investment amount. Thus, the viability of the investment is straightly tied to the region where the wind turbine is installed, and the government incentives may allow decreasing in the investment amount for wind power. Based on this, incentives programs for the production of clean energy include cheaper purchase of wind turbines, lower taxing and financing rates, can make wind power more profitable and attractive.
Study on Selecting the Optimal Algorithm and the Effective Methodology to ANN-Based Short-Term Load Forecasting Model for the Southern Power Company in Vietnam
Authors: Pham Manh-Hai , Vu T-A-Tho , Nguyen Duc-Quang , Dang Viet-Hung , Nguyen Ngoc-Trung , Dang Thu-Huyen , Nguyen The Vinh
Published: June 2019

Recently, power companies apply optimal algorithms for short-term load forecasting, especially the daily load. However, in Vietnam, the load forecasting of the power system has not focused on this solution. Optimal algorithms and can help experts improve forecasting results including accuracy and the time required for forecasting. To achieve both goals, the combinations of different algorithms are still being studied. This article describes research using a new combination of two optimal algorithms: Genetic Algorithm (GA) and Particle Swarm Optimization (PSO). This combination limits the weakness of the convergence speed of GA as well as the weakness of PSO that it easily falls into local optima (thereby reducing accuracy). This new hybrid algorithm was applied to the Southern Power Corporation’s (SPC—a large Power company in Vietnam) daily load forecasting. The results show the algorithm’s potential to provide a solution. The most accurate result was for the forecasting of a normal working day with an average error of 1.15% while the largest error was 3.74% and the smallest was 0.02%. For holidays and weekends, the average error always approximated the allowable limit of 3%. On the other hand, some poor results also provide an opportunity to re-check the real data provided by SPC.
Modeling Dynamics of Structural Components of Forest Stands Based on Trivariate Stochastic Differential Equation
Authors: Rupšys Petras
Published: June 2019

Research Highlights: Today’s approaches to modeling of forest stands are in most cases based on that the regression models and they are constructed as static sub-models describing individual stands variables. The disadvantages of this method; it is laborious because too many different equations need to be assessed and empirical choices of candidate equations make the results subjective; it does not relate to the stand variables dynamics against the age dimension (time); and does not consider the underlying covariance structure driving changes in the stand variables. In this study, the dynamical model defined by a fixed-and mixed effect parameters trivariate stochastic differential equation (SDE) is introduced and described how such a model can be used to model quadratic mean diameter, mean height, number of trees per hectare, self-thinning line, stand basal area, stand volume per hectare and much more. Background and Objectives: New developed marginal and conditional trivariate probability density functions, combining information generated from an age-dependent variance-covariance matrix of quadratic mean diameter, mean height and number of trees per hectare, improve stand growth prediction, and forecast (in forecast the future is completely unavailable and must only be estimated from historical patterns) accuracies. Materials and Methods: Fixed-and mixed effect parameters SDE models were harmonized to predict and forecast the dynamics of quadratic mean diameter, mean height, number of trees per hectare, basal area, stand volume per hectare, and their current and mean increments. The results and experience from applying the SDE concepts and techniques in an extensive whole stand growth and yield analysis are described using a Scots pine (Pinus sylvestris L.) experimental dataset in Lithuania. Results: The mixed effects scenario SDE model showed high accuracy, the percentage root mean square error values for quadratic mean diameter, mean height, number of trees per hectare, stand basal area and stand volume per hectare predictions (forecasts) were 3.37% (10.44%), 1.82% (2.07%), 1.76% (2.93%), 6.65% (10.41%) and 6.50% (8.93%), respectively. In the same way, the quadratic mean diameter, mean height, number of trees per hectare, stand basal area and stand volume per hectare prediction (forecast) relationships had high values of the coefficient of determination, R2, 0.998 (0.987), 0.997 (0.992), 0.997 (0.988), 0.968 (0.984) and 0.966 (0.980), respectively. Conclusions: The approach presented in this paper can be used for developing a new generation stand growth and yield models.
Effects of Climate Change at Treeline: Lessons from Space-for-Time Studies, Manipulative Experiments, and Long-Term Observational Records in the Central Austrian Alps
Authors: Wieser Gerhard , Oberhuber Walter , Gruber Andreas
Published: June 2019

This review summarizes the present knowledge about effects of climate change on conifers within the treeline ecotone of the Central Austrian Alps. After examining the treeline environment and the tree growth with respect to elevation, possible effects of climate change on carbon gain and water relations derived from space-for-time studies and manipulative experiments are outlined. Finally, long-term observational records are discussed, working towards conclusions on tree growth in a future, warmer environment. Increases in CO2 levels along with climate warming interact in complex ways on trees at the treeline. Because treeline trees are not carbon limited, climate warming (rather than the rising atmospheric CO2 level) causes alterations in the ecological functioning of the treeline ecotone in the Central Austrian Alps. Although the water uptake from soils is improved by further climate warming due to an increased permeability of root membranes and aquaporin-mediated changes in root conductivity, tree survival at the treeline also depends on competitiveness for belowground resources. The currently observed seedling re-establishment at the treeline in the Central European Alps is an invasion into potential habitats due to decreasing grazing pressure rather than an upward-migration due to climate warming, suggesting that the treeline in the Central Austrian Alps behaves in a conservative way. Nevertheless, to understand the altitude of the treeline, one must also consider seedling establishment. As there is a lack of knowledge on this particular topic within the treeline ecotone in the Central Austrian Alps, we conclude further research has to focus on the importance of this life stage for evaluating treeline shifts and limits in a changing environment.
The cGMP Pathway and Inherited Photoreceptor Degeneration: Targets, Compounds, and Biomarkers
Authors: Tolone Arianna , Belhadj Soumaya , Rentsch Andreas , Schwede Frank , Paquet-Durand François
Published: June 2019

Photoreceptor physiology and pathophysiology is intricately linked to guanosine-3’,5’-cyclic monophosphate (cGMP)-signaling. Here, we discuss the importance of cGMP-signaling for the pathogenesis of hereditary retinal degeneration. Excessive accumulation of cGMP in photoreceptors is a common denominator in cell death caused by a variety of different gene mutations. The cGMP-dependent cell death pathway may be targeted for the treatment of inherited photoreceptor degeneration, using specifically designed and formulated inhibitory cGMP analogues. Moreover, cGMP-signaling and its down-stream targets may be exploited for the development of novel biomarkers that could facilitate monitoring of disease progression and reveal the response to treatment in future clinical trials. We then briefly present the importance of appropriate formulations for delivery to the retina, both for drug and biomarker applications. Finally, the review touches on important aspects of future clinical translation, highlighting the need for interdisciplinary cooperation of researchers from a diverse range of fields.
A SIX6 Nonsense Variant in Golden Retrievers with Congenital Eye Malformations
Authors: Hug Petra , Anderegg Linda , Dürig Nicole , Lepori Vincent , Jagannathan Vidhya , Spiess Bernhard , Richter Marianne , Leeb Tosso
Published: June 2019

Causative genetic variants for more than 30 heritable eye disorders in dogs have been reported. For other clinically described eye disorders, the genetic cause is still unclear. We investigated four Golden Retriever litters segregating for highly variable congenital eye malformations. Several affected puppies had unilateral or bilateral retina dysplasia and/or optic nerve hypoplasia. The four litters shared the same father or grandfather suggesting a heritable condition with an autosomal dominant mode of inheritance. The genome of one affected dog was sequenced and compared to 601 control genomes. A heterozygous private nonsense variant, c.487C>T, was found in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*). We genotyped all available family members and 464 unrelated Golden Retrievers. All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases. The SIX6 protein is a homeobox transcription factor with a known role in eye development. In humans and other species, SIX6 loss of function variants were reported to cause congenital eye malformations. This strongly suggests that the c.487C>T variant detected contributed to the observed eye malformations. We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs.
Hospitalization Rates for Respiratory Diseases After L’Aquila Earthquake
Authors: D’Aloisio Francesco , Vittorini Pierpaolo , Giuliani Anna Rita , Scatigna Maria , Del Papa Jacopo , Muselli Mario , Baccari Giorgio , Fabiani Leila
Published: June 2019

The study aims to investigate the impact of the earthquake on public health, in terms of hospitalizations for respiratory diseases in the Abruzzo region, focusing on the area damaged by the earthquake “Crater”. We collected data of hospitalizations of residents in Abruzzo between 2009 and 2015. Hospital Discharge Records (HDRs) with a primary diagnosis of respiratory disease were included and divided into pneumonia, Chronic Obstructive Pulmonary Disease (COPD), and respiratory insufficiency. Absolute frequencies and standardized hospitalization rates were calculated to perform both a short-term and a medium-long term analysis. A linear regression was performed using standardized hospitalization rates and the time. A total of 108.669 respiratory-related records were collected and the most frequent subgroup was respiratory insufficiency. Standardized Hospitalization Rates (SHRs) for respiratory diseases resulted higher in the non-Crater than Crater area, but the short-term analysis showed a significant increase in hospitalizations for pneumonia and respiratory insufficiency in the Crater area. The medium-long term analysis reported a significant difference on the slope decrease of hospitalizations for acute and chronic respiratory diseases in the Crater versus the non-Crater area. The earthquake may have played a triggering role in the increased detection of respiratory diseases. A temporal relationship between the quake and an increase in admissions was found although it is not yet possible to detect a direct cause-effect relationship.
When and How Do Emotional Intelligence and Flourishing Protect against Suicide Risk in Adolescent Bullying Victims?
Authors: Rey Lourdes , Mérida-López Sergio , Sánchez-Álvarez Nicolás , Extremera Natalio
Published: June 2019

This study contributes to current knowledge on the protective role of emotional intelligence and flourishing in cases of suicide risk (namely depressive symptoms and suicidal ideation) in a sample of adolescent victims of traditional bullying. The proposed model tested the mediator role of flourishing in the relationship between emotional intelligence (EI) and suicide risk together with the moderating effect of EI in the relationship between low flourishing and increased suicide risk. Considering an initial sample of 1847 adolescents (52.5% female), a subsample of 494 pure bullying victims (61.3% female) took part in this research. The main results showed EI to be linked to decreased suicide risk through levels of flourishing. Moreover, EI buffered the relationship between low flourishing and the associated suicide risk. Victimized adolescents with both low levels of EI and of flourishing reported higher levels of suicide risk than their counterparts with high EI levels. This suggests the protective role of EI of both predicting higher flourishing and reducing the likelihood of suicide risk among victimized adolescents with low levels of flourishing. Finally, the practical implications of these novel findings regarding the role of EI and flourishing in the prevention of suicide risk among victimized adolescents are discussed.
Impact of Extremely Hot Days on Emergency Department Visits for Cardiovascular Disease among Older Adults in New York State
Authors: Li Mengxuan , Shaw Benjamin A. , Zhang Wangjian , Vásquez Elizabeth , Lin Shao
Published: June 2019

Prior studies have reported the impact of ambient heat exposure on heat-related illnesses and mortality in summer, but few have assessed its effect on cardiovascular diseases (CVD) morbidity, and the association difference by demographics and season. This study examined how extremely hot days affected CVD-related emergency department (ED) visits among older adults from 2005–2013 in New York State. A time-stratified case-crossover design was used to assess the heat–CVD association in summer and transitional months (April–May and September–October). Daily mean temperature >95th percentile of regional monthly mean temperature was defined as an extremely hot day. Extremely hot days were found to be significantly associated with increased risk of CVD-related ED visits at lag day 5 (OR: 1.02, 95% CI: 1.01–1.04) and lag day 6 (OR: 1.01, 95% CI: 1.00–1.03) among older adults in summer after controlling for PM2.5 concentration, relative humidity, and barometric pressure. Specifically, there was a 7% increased risk of ischemic heart disease on the day of extreme heat, and increased risks of hypertension (4%) and cardiac dysrhythmias (6%) occurred on lag days 5 and 6, respectively. We also observed large geographic variations in the heat–CVD associations.
Temporal Trends in Fecal Occult Blood Test: Associated Factors (2009–2017)
Authors: Cobo-Cuenca Ana Isabel , Laredo-Aguilera José Alberto , Rodríguez-Borrego María-Aurora , Santacruz-Salas Esmeralda , Carmona-Torres Juan Manuel
Published: June 2019

A cross-sectional study with 27,821 records of non-institutionalized people in Spain aged between 50–69 years old (59.94 ± 5.8 years), who participated in the European Health Survey in Spain (2009, 2014) and National Health Survey (2011/12, 2017). Fecal occult testing, the reason for performing the test, age, sex, nationality, social status, marital status, education level, body mass index (BMI), and place of residence. Overall, 54% were women, 93.9% were Spanish, 47.8% had a secondary study, and 66.4% were married. Across the years, the rate of the fecal occult blood test (FOBT) increased significantly (p < 0.001). This increase can be accounted for a letter campaign advising testing (45%, p < 0.001). FOBT was associated with more age (odds ratio—OR 1.04, 95% confidence interval—CI 1.04–1.05, p < 0.001), Spanish nationality (OR 1.91, 95% CI 1.25–2.93, p = 0.003), being married (OR 1.13, 95% CI 1.02–1.25, p = 0.025), having a higher level of education (OR 2.46, 95% CI 2.17–2.81, p < 0.001), belonging to high social classes (OR 1.35, 95% CI 1.12–1.64, p = 0.001), and BMI <25 (OR 1.72, 95% CI 1.25–2.37). Frequency of FOBT has increased in recent years. Performing FOBT is associated with age, nationality, marital status, higher education level, and social class.
Cellular Effects of Butyrate on Vascular Smooth Muscle Cells are Mediated through Disparate Actions on Dual Targets, Histone Deacetylase (HDAC) Activity and PI3K/Akt Signaling Network
Authors: Mathew Omana P. , Ranganna Kasturi , Mathew Joseph , Zhu Meiling , Yousefipour Zivar , Selvam Chelliah , Milton Shirlette G.
Published: June 2019

Vascular remodeling is a characteristic feature of cardiovascular diseases. Altered cellular processes of vascular smooth muscle cells (VSMCs) is a crucial component in vascular remodeling. Histone deacetylase inhibitor (HDACI), butyrate, arrests VSMC proliferation and promotes cell growth. The objective of the study is to determine the mechanism of butyrate-induced VSMC growth. Using proliferating VSMCs exposed to 5 mM butyrate, immunoblotting studies are performed to determine whether PI3K/Akt pathway that regulates different cellular effects is a target of butyrate-induced VSMC growth. Butyrate inhibits phosphorylation-dependent activation of PI3K, PDK1, and Akt, eliciting differential effects on downstream targets of Akt. Along with previously reported Ser9 phosphorylation-mediated GSK3 inactivation leading to stability, increased expression and accumulation of cyclin D1, and epigenetic histone modifications, inactivation of Akt by butyrate results in: transcriptional activation of FOXO1 and FOXO3 promoting G1 arrest through p21Cip1/Waf1 and p15INK4B upregulation; inactivation of mTOR inhibiting activation of its targets p70S6K and 4E-BP1 impeding protein synthesis; inhibition of caspase 3 cleavage and downregulation of PARP preventing apoptosis. Our findings imply butyrate abrogates Akt activation, causing differential effects on Akt targets promoting convergence of cross-talk between their complimentary actions leading to VSMC growth by arresting proliferation and inhibiting apoptosis through its effect on dual targets, HDAC activity and PI3K/Akt pathway network.
Transcriptomic Studies Reveal that the Rhizobium leguminosarum Serine/Threonine Protein Phosphatase PssZ has a Role in the Synthesis of Cell-Surface Components, Nutrient Utilization, and Other Cellular Processes
Authors: Lipa Paulina , Vinardell José-María , Janczarek Monika
Published: June 2019

Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing symbiotic associations with clover plants (Trifolium spp.). Surface polysaccharides, transport systems, and extracellular components synthesized by this bacterium are required for both the adaptation to changing environmental conditions and successful infection of host plant roots. The pssZ gene located in the Pss-I region, which is involved in the synthesis of extracellular polysaccharide, encodes a protein belonging to the group of serine/threonine protein phosphatases. In this study, a comparative transcriptomic analysis of R. leguminosarum bv. trifolii wild-type strain Rt24.2 and its derivative Rt297 carrying a pssZ mutation was performed. RNA-Seq data identified a large number of genes differentially expressed in these two backgrounds. Transcriptome profiling of the pssZ mutant revealed a role of the PssZ protein in several cellular processes, including cell signalling, transcription regulation, synthesis of cell-surface polysaccharides and components, and bacterial metabolism. In addition, we show that inactivation of pssZ affects the rhizobial ability to grow in the presence of different sugars and at various temperatures, as well as the production of different surface polysaccharides. In conclusion, our results identified a set of genes whose expression was affected by PssZ and confirmed the important role of this protein in the rhizobial regulatory network.
Fine Mapping of Glutamate Decarboxylase 65 Epitopes Reveals Dependency on Hydrophobic Amino Acids for Specific Interactions
Authors: Valdarnini Niccolò , Holm Bettina , Hansen Paul , Rovero Paolo , Houen Gunnar , Trier Nicole
Published: June 2019

Characterization of multiple antibody epitopes has revealed the necessity of specific groups of amino acid residues for reactivity. This applies to the majority of antibody–antigen interactions, where especially charged and hydrophilic amino acids have been reported to be essential for antibody reactivity. This study describes thorough characterization of glutamic acid decarboxylase (GAD) 65 antigenic epitopes, an immunodominant autoantigen in type 1 diabetes (T1D). As linear epitopes are sparsely described for GAD65 in T1D, we aimed to identify and thoroughly characterize two GAD65 antibodies using immunoassays. A monoclonal antibody recognized an epitope in the N-terminal domain of GAD65, 8FWSFGSE14, whereas a polyclonal antibody recognized two continuous epitopes in the C-terminal domain, corresponding to amino acids 514RTLED518 and 549PLGDKVNF556. Hydrophobic amino acids were essential for antibody reactivity, which was verified by competitive inhibition assays. Moreover, the epitopes were located in flexible linker regions and turn structures. These findings confirm the versatile nature of antibody–antigen interactions and describe potential continuous epitopes related to T1D, which predominantly have been proposed to be of discontinuous nature.
Curcumin-Loaded Mesoporous Silica Nanoparticles Markedly Enhanced Cytotoxicity in Hepatocellular Carcinoma Cells
Authors: Kong Zwe-Ling , Kuo Hsiang-Ping , Johnson Athira , Wu Li-Cyuan , Chang Ke Liang B.
Published: June 2019

Curcumin, a natural polyphenol extracted from a perennial herb Curcuma longa has been verified for many physiological activities such as anti-oxidant, anti-inflammatory, and anti-tumor properties. The direct use of curcumin cytotoxicity studies are limited due to its unstable chemical structure, low bioavailability, easy oxidation, and degradation by ultraviolet (UV) light etc. Trying to overcome this problem, silica-encapsulated curcumin nanoparticles (SCNP) and chitosan with silica co-encapsulated curcumin nanoparticles (CSCNP) were prepared by silicification and biosilicification methods, respectively, and encapsulated curcumin within it. We investigated the antitumor properties of SCNP and CSCNP on different tumor cell lines. Scanning electron microscopy (SEM) analysis revealed that both SCNP and CSCNP were almost spherical in shape and the average particle size of CSCNP was 75.0 ± 14.62 nm, and SCNP was 61.7 ± 23.04 nm. The results show that CSCNP has more anti-oxidant activity as compared to curcumin and SCNP. The higher cytotoxicity towards different cancerous cell lines was also observed in CSCNP treated tumor cells. It was noted that the SCNP and CSCNP has a high percentage of IC50 values in Hep G2 cells. The encapsulation of curcumin improved instability, antioxidant activity, and antitumor activity. Our results demonstrated that nanoencapsulation of curcumin with silica and chitosan not only increase curcumin stability but also enhance its cytotoxic activity on hepatocellular carcinoma cells. On the basis of these primary studies, the curcumin-loaded nanoparticles appear to be promising as an innovative therapeutic material for the treatment of tumors.
Antimicrobial Gold Nanoclusters: Recent Developments and Future Perspectives
Authors: Yougbare Sibidou , Chang Ting-Kuang , Tan Shih-Hua , Kuo Jui-Chi , Hsu Po-Hsuan , Su Chen-Yen , Kuo Tsung-Rong
Published: June 2019

Bacterial infections have caused serious threats to public health due to the antimicrobial resistance in bacteria. Recently, gold nanoclusters (AuNCs) have been extensively investigated for biomedical applications because of their superior structural and optical properties. Great efforts have demonstrated that AuNCs conjugated with various surface ligands are promising antimicrobial agents owing to their high biocompatibility, polyvalent effect, easy modification and photothermal stability. In this review, we have highlighted the recent achievements for the utilizations of AuNCs as the antimicrobial agents. We have classified the antimicrobial AuNCs by their surface ligands including small molecules (<900 Daltons) and macromolecules (>900 Daltons). Moreover, the antimicrobial activities and mechanisms of AuNCs have been introduced into two main categories of small molecules and macromolecules, respectively. In accordance with the advancements of antimicrobial AuNCs, we further provided conclusions of current challenges and recommendations of future perspectives of antimicrobial AuNCs for fundamental researches and clinical applications.
Comparison of Functional Components and Antioxidant Activity of Lycium barbarum L. Fruits from Different Regions in China
Authors: Lu Youyuan , Guo Sheng , Zhang Fang , Yan Hui , Qian Da-Wei , Wang Han-Qing , Jin Ling , Duan Jin-Ao
Published: June 2019

The fruit of Lycium barbarum L. (FLB) has been used as medicines and functional foods for more than 2000 years in East Asia. In this study, carotenoid, phenolic, flavonoid, and polysaccharide contents as well as the antioxidant activities of FLB from 13 different regions in China from a total of 78 samples were analyzed. The results showed that total carotenoid contents ranged from 12.93 to 25.35 mg β-carotene equivalents/g DW. Zeaxanthin dipalmitate was the predominant carotenoid (4.260–10.07 mg/g DW) in FLB. The total phenolic, total flavonoid, and total polysaccharide contents ranged from 6.899 to 8.253 mg gallic acid equivalents/g DW, 3.177 to 6.144 mg rutin equivalents/g DW, and 23.62 to 42.45 mg/g DW, respectively. Rutin content ranged from 0.1812 to 0.4391 mg/g DW, and ferulic acid content ranged from 0.0994 to 0.1726 mg/g DW. All of these FLB could be divided into two clusters with PCA analysis, and both individual carotenoids and total carotenoid contents could be used as markers for regional characterization. The phenolic components were the main substance for the antioxidant activity of FLB. Considering the functional component and antioxidant activities, FLB produced in Guyuan of Ningxia was the closest to Daodi herbs (Zhongwei of Ningxia), which is commercially available high quality FLB. The results of this study could provide guidance for comprehensive applications of FLB production in different regions.
A Novel Cold-Adapted and Salt-Tolerant RNase R from Antarctic Sea-Ice Bacterium Psychrobacter sp. ANT206
Authors: Wang Yatong , Hou Yanhua , Nie Ping , Wang Yifan , Ren Xiulian , Wei Qifeng , Wang Quanfu
Published: June 2019

A novel RNase R, psrnr, was cloned from the Antarctic bacterium Psychrobacter sp. ANT206 and expressed in Escherichia coli (E. coli). A bioinformatics analysis of the psrnr gene revealed that it contained an open reading frame of 2313 bp and encoded a protein (PsRNR) of 770 amino acids. Homology modeling indicated that PsRNR had reduced hydrogen bonds and salt bridges, which might be the main reason for the catalytic efficiency at low temperatures. A site directed mutation exhibited that His 667 in the active site was absolutely crucial for the enzyme catalysis. The recombinant PsRNR (rPsRNR) showed maximum activity at 30 °C and had thermal instability, suggesting that rPsRNR was a cold-adapted enzyme. Interestingly, rPsRNR displayed remarkable salt tolerance, remaining stable at 0.5–3.0 M NaCl. Furthermore, rPsRNR had a higher kcat value, contributing to its efficient catalytic activity at a low temperature. Overall, cold-adapted RNase R in this study was an excellent candidate for antimicrobial treatment.
Therapeutic Potential and Biological Applications of Cordycepin and Metabolic Mechanisms in Cordycepin-Producing Fungi
Authors: Qin Peng , Li XiangKai , Yang Hui , Wang Zhi-Ye , Lu DengXue
Published: June 2019

Cordycepin (3′-deoxyadenosine), a cytotoxic nucleoside analogue found in Cordyceps militaris, has attracted much attention due to its therapeutic potential and biological value. Cordycepin interacts with multiple medicinal targets associated with cancer, tumor, inflammation, oxidant, polyadenylation of mRNA, etc. The investigation of the medicinal drug actions supports the discovery of novel targets and the development of new drugs to enhance the therapeutic potency and reduce toxicity. Cordycepin may be of great value owing to its medicinal potential as an external drug, such as in cosmeceutical, traumatic, antalgic and muscle strain applications. In addition, the biological application of cordycepin, for example, as a ligand, has been used to uncover molecular structures. Notably, studies that investigated the metabolic mechanisms of cordycepin-producing fungi have yielded significant information related to the biosynthesis of high levels of cordycepin. Here, we summarized the medicinal targets, biological applications, cytotoxicity, delivery carriers, stability, and pros/cons of cordycepin in clinical applications, as well as described the metabolic mechanisms of cordycepin in cordycepin-producing fungi. We posit that new approaches, including single-cell analysis, have the potential to enhance medicinal potency and unravel all facets of metabolic mechanisms of cordycepin in Cordyceps militaris.
Accelerating Drug Discovery by Early Protein Drug Target Prediction Based on a Multi-Fingerprint Similarity Search †
Authors: Montaruli Michele , Alberga Domenico , Ciriaco Fulvio , Trisciuzzi Daniela , Tondo Anna Rita , Mangiatordi Giuseppe Felice , Nicolotti Orazio
Published: June 2019

In this continuing work, we have updated our recently proposed Multi-fingerprint Similarity Search algorithm (MuSSel) by enabling the generation of dominant ionized species at a physiological pH and the exploration of a larger data domain, which included more than half a million high-quality small molecules extracted from the latest release of ChEMBL (version 24.1, at the time of writing). Provided with a high biological assay confidence score, these selected compounds explored up to 2822 protein drug targets. To improve the data accuracy, samples marked as prodrugs or with equivocal biological annotations were not considered. Notably, MuSSel performances were overall improved by using an object-relational database management system based on PostgreSQL. In order to challenge the real effectiveness of MuSSel in predicting relevant therapeutic drug targets, we analyzed a pool of 36 external bioactive compounds published in the Journal of Medicinal Chemistry from October to December 2018. This study demonstrates that the use of highly curated chemical and biological experimental data on one side, and a powerful multi-fingerprint search algorithm on the other, can be of the utmost importance in addressing the fate of newly conceived small molecules, by strongly reducing the attrition of early phases of drug discovery programs.
Parabiosis Incompletely Reverses Aging-Induced Metabolic Changes and Oxidant Stress in Mouse Red Blood Cells
Authors: Morrison Evan J. , Champagne Devin P. , Dzieciatkowska Monika , Nemkov Travis , Zimring James C. , Hansen Kirk C. , Guan Fangxia , Huffman Derek M. , Santambrogio Laura , D’Alessandro Angelo
Published: June 2019

Mature red blood cells (RBCs) not only account for ~83% of the total host cells in the human body, but they are also exposed to all body tissues during their circulation in the bloodstream. In addition, RBCs are devoid of de novo protein synthesis capacity and, as such, they represent a perfect model to investigate system-wide alterations of cellular metabolism in the context of aging and age-related oxidant stress without the confounding factor of gene expression. In the present study, we employed ultra-high-pressure liquid chromatography coupled with mass spectrometry (UHPLC–MS)-based metabolomics and proteomics to investigate RBC metabolism across age in male mice (6, 15, and 25 months old). We report that RBCs from aging mice face a progressive decline in the capacity to cope with oxidant stress through the glutathione/NADPH-dependent antioxidant systems. Oxidant stress to tryptophan and purines was accompanied by declines in late glycolysis and methyl-group donors, a potential compensatory mechanism to repair oxidatively damaged proteins. Moreover, heterochronic parabiosis experiments demonstrated that the young environment only partially rescued the alterations in one-carbon metabolism in old mice, although it had minimal to no impact on glutathione homeostasis, the pentose phosphate pathway, and oxidation of purines and tryptophan, which were instead aggravated in old heterochronic parabionts.
CK2 Pro-Survival Role in Prostate Cancer Is Mediated via Maintenance and Promotion of Androgen Receptor and NFκB p65 Expression
Authors: Trembley Janeen H. , Kren Betsy T. , Abedin Md. J. , Shaughnessy Daniel P. , Li Yingming , Dehm Scott M. , Ahmed Khalil
Published: June 2019

The prosurvival protein kinase CK2, androgen receptor (AR), and nuclear factor kappa B (NFκB) interact in the function of prostate cells, and there is evidence of crosstalk between these signals in the pathobiology of prostate cancer (PCa). As CK2 is elevated in PCa, and AR and NFκB are involved in the development and progression of prostate cancer, we investigated their interaction in benign and malignant prostate cells in the presence of altered CK2 expression. Our results show that elevation of CK2 levels caused increased levels of AR and NFκB p65 in prostate cells of different phenotypes. Analysis of TCGA PCa data indicated that AR and CK2α RNA expression are strongly correlated. Small molecule inhibition or molecular down-regulation of CK2 caused reduction in AR mRNA expression and protein levels in PCa cells and in orthotopic xenograft tumors by various pathways. Among these, regulation of AR protein stability plays a unifying role in CK2 maintenance of AR protein levels. Our results show induction of various endoplasmic reticulum stress signals after CK2 inhibition, which may play a role in the PCa cell death response. Of note, CK2 inhibition caused loss of cell viability in both parental and enzalutamide-resistant castrate-resistant PCa cells. The present work elucidates the specific link of CK2 to the pathogenesis of PCa in association with AR and NFκB expression; further, the observation that inhibition of CK2 can exert a growth inhibitory effect on therapy-resistant PCa cells emphasizes the potential utility of CK2 inhibition in patients who are on enzalutamide treatment for advanced cancer.
Epoprostenol Delivered via High Flow Nasal Cannula for ICU Subjects with Severe Hypoxemia Comorbid with Pulmonary Hypertension or Right Heart Dysfunction
Authors: Li Jie , Harnois Lauren J. , Markos Bethelhem , Roberts Keith M. , Homoud Salma Al , Liu Jing , Mirza Sara , Vines David
Published: June 2019

Inhaled epoprostenol (iEPO) has been utilized to improve oxygenation in mechanically ventilated subjects with severe hypoxemia, but the evidence for iEPO via high-flow nasal cannula (HFNC) is rare. Following approval by the institutional review board, this retrospective cohort study evaluated subjects who received iEPO via HFNC for more than 30 min to treat severe hypoxemia comorbid with pulmonary hypertension or right heart dysfunction between July 2015 and April 2018. A total of 11 subjects were enrolled in the study of whom 4 were male (36.4%), age 57.5 ± 22.1 years, and APACHE II score at ICU admission was 18.5 ± 5.7. Ten subjects had more than three chronic heart or lung comorbidities; seven of them used home oxygen. After inhaling epoprostenol, subjects’ SpO2/FIO2 ratio improved from 107.5 ± 26.3 to 125.5 ± 31.6 (p = 0.026) within 30–60 min. Five subjects (45.5%) had SpO2/FIO2 improvement >20%, which was considered as a positive response. Heart rate, blood pressure, and respiratory rate were not significantly different. Seven subjects did not require intubation, and seven subjects were discharged home. This retrospective study demonstrated the feasibility of iEPO via HFNC in improving oxygenation. Careful titration of flow while evaluating subjects’ response may help identify responders and avoid delaying other interventions. This study supports the need for a larger prospective randomized control trial to further evaluate the efficacy of iEPO via HFNC in improving outcomes.
Super-Higgs in Superspace
Authors: Tallarita Gianni , McGarrie Moritz
Published: June 2019

We determine the effective gravitational couplings in superspace whose components reproduce the supergravity Higgs effect for the constrained Goldstino multiplet. It reproduces the known Gravitino sector while constraining the off-shell completion. We show that these couplings arise by computing them as quantum corrections. This may be useful for phenomenological studies and model-building. We give an example of its application to multiple Goldstini.
One-Pot Method of Synthesizing TEMPO-Oxidized Bacterial Cellulose Nanofibers Using Immobilized TEMPO for Skincare Applications
Authors: Jun Seung-Hyun , Park Sun-Gyoo , Kang Nae-Gyu
Published: June 2019

In the skincare field, water-dispersed bacterial cellulose nanofibers synthesized via an oxidation reaction using 2,2,6,6–tetramethyl–1–piperidine–N–oxy radical (TEMPO) as a catalyst are promising bio-based polymers for engineered green materials because of their unique properties when applied to the surface of the skin, such as a high tensile strength, high water-holding capacity, and ability to block harmful substances. However, the conventional method of synthesizing TEMPO-oxidized bacterial cellulose nanofibers (TOCNs) is difficult to scale due to limitations in the centrifuge equipment when treating large amounts of reactant. To address this, we propose a one-pot TOCN synthesis method involving TEMPO immobilized on silica beads that employs simple filtration instead of centrifugation after the oxidation reaction. A comparison of the structural and physical properties of the TOCNs obtained via the proposed and conventional methods found similar properties in each. Therefore, it is anticipated that due to its simplicity, efficiency, and ease of use, the proposed one-pot synthesis method will be employed in production scenarios to prepare production quantities of bio-based polymer nanofibers in various potential industrial applications in the fields of skincare and biomedical research.
AGB Estimation in a Tropical Mountain Forest (TMF) by Means of RGB and Multispectral Images Using an Unmanned Aerial Vehicle (UAV)
Authors: González-Jaramillo Víctor , Fries Andreas , Bendix Jörg
Published: June 2019

The present investigation evaluates the accuracy of estimating above-ground biomass (AGB) by means of two different sensors installed onboard an unmanned aerial vehicle (UAV) platform (DJI Inspire I) because the high costs of very high-resolution imagery provided by satellites or light detection and ranging (LiDAR) sensors often impede AGB estimation and the determination of other vegetation parameters. The sensors utilized included an RGB camera (ZENMUSE X3) and a multispectral camera (Parrot Sequoia), whose images were used for AGB estimation in a natural tropical mountain forest (TMF) in Southern Ecuador. The total area covered by the sensors included 80 ha at lower elevations characterized by a fast-changing topography and different vegetation covers. From the total area, a core study site of 24 ha was selected for AGB calculation, applying two different methods. The first method used the RGB images and applied the structure for motion (SfM) process to generate point clouds for a subsequent individual tree classification. Per the classification at tree level, tree height (H) and diameter at breast height (DBH) could be determined, which are necessary input parameters to calculate AGB (Mg ha−1) by means of a specific allometric equation for wet forests. The second method used the multispectral images to calculate the normalized difference vegetation index (NDVI), which is the basis for AGB estimation applying an equation for tropical evergreen forests. The obtained results were validated against a previous AGB estimation for the same area using LiDAR data. The study found two major results: (i) The NDVI-based AGB estimates obtained by multispectral drone imagery were less accurate due to the saturation effect in dense tropical forests, (ii) the photogrammetric approach using RGB images provided reliable AGB estimates comparable to expensive LiDAR surveys (R2: 0.85). However, the latter is only possible if an auxiliary digital terrain model (DTM) in very high resolution is available because in dense natural forests the terrain surface (DTM) is hardly detectable by passive sensors due to the canopy layer, which impedes ground detection.