bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting CD28 Superagonist TGN1412 as Potential Therapeutic for Pediatric B Cell Leukemia: A Review
Authors: Brown Katelyn E.
Published: May 2018

Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell. This drug was intended as a solution to T cell deficient diseases such as B cell leukemia and autoimmune diseases such as rheumatoid arthritis. When phase I clinical trials were conducted, all volunteers that received the drug experienced severe cytokine release syndrome (CRS) and faced multiple-organ failure within hours. TGN1412 was reassessed and re-entered clinical trials as a therapeutic for rheumatoid arthritis. A new assay was developed to better quantify T cell response, and volunteers in this trial experienced no pro-inflammatory cytokine release. This essay analyzes how misinformation contributed to the failure of TGN1412 in clinical trials and how revisiting this therapeutic could yield a novel treatment for pediatric B cell leukemia.
Oral and Dental Health Status among Adolescents with Limited Access to Dental Care Services in Jeddah
Authors: Bahannan Salma A. , Eltelety Somaya M. , Hassan Mona H. , Ibrahim Suzan S. , Amer Hala A. , El Meligy Omar A. , Al-Johani Khalid A. , Kayal Rayyan A. , Mokeem Abeer A. , Qutob Akram F. , Mira Abdulghani I.
Published: May 2018

The purpose of this study was to assess the prevalence and associated factors of dental caries and periodontal diseases among 14–19-year-old schoolchildren with limited access to dental care services. A cross sectional study design was conducted during field visits to seven governmental schools in Al-Khomrah district, South Jeddah, over the period from September 2015 to May 2016. Clinical examinations and administered questionnaires were carried out in mobile dental clinics. The dentists carried out oral examinations using the dental caries index (DMFT), the simplified oral hygiene index (OHI-S), and the community periodontal index for treatment needs (CPITN). Statistical analyses were performed using SPSS 20. A total of 734 schoolchildren were examined. The prevalence of decayed teeth was 79.7% and was significantly higher among boys (88.9%) than girls (69.0%). About 11% of students had missing teeth, with a significantly higher figure among females than males (15.9% versus 7.3%); 19.8% of students had filled teeth. Moreover, a DMFT of seven or more was significantly more prevalent among males (43.3%) than females (26.8%), while the percentage of females with sound teeth was significantly higher than for males (20.4% and 9.6% respectively). The CPITN revealed 0, 1 and 2 scores among 14.6%, 78.2%, and 41.6% respectively. Males had a significantly higher percentage of healthy periodontal condition (23.8%) than females (3.8%). Dental caries prevalence was moderate to high, calculus and gingival bleeding were widespread among schoolchildren, and were more prevalent among students with low socioeconomic status.
On f-Divergences: Integral Representations, Local Behavior, and Inequalities
Authors: Sason Igal
Published: May 2018

This paper is focused on f-divergences, consisting of three main contributions. The first one introduces integral representations of a general f-divergence by means of the relative information spectrum. The second part provides a new approach for the derivation of f-divergence inequalities, and it exemplifies their utility in the setup of Bayesian binary hypothesis testing. The last part of this paper further studies the local behavior of f-divergences.
Johansen’s Reduced Rank Estimator Is GMM
Authors: Hansen Bruce E.
Published: May 2018

The generalized method of moments (GMM) estimator of the reduced-rank regression model is derived under the assumption of conditional homoscedasticity. It is shown that this GMM estimator is algebraically identical to the maximum likelihood estimator under normality developed by Johansen (1988). This includes the vector error correction model (VECM) of Engle and Granger. It is also shown that GMM tests for reduced rank (cointegration) are algebraically similar to the Gaussian likelihood ratio tests. This shows that normality is not necessary to motivate these estimators and tests.
A Miniaturized Electromagnetic Bandgap Structure Using an Inductance-Enhanced Patch for Suppression of Parallel Plate Modes in Packages and PCBs
Authors: Kim Myunghoi
Published: May 2018

In the packages and printed circuit boards (PCBs) of high-speed and mixed-signal electronics, parallel plate waveguides (PPWs) are frequently used as the power/ground plane pair, resulting in a significant problem of electrical switching noise such as simultaneous switching noise and ground bounce noise. This noise inevitably deteriorates system performance. In this paper, we propose an electromagnetic bandgap (EBG) structure using an inductance-enhanced patch (IEP) to suppress PPW modes in high-speed and compact packages and PCBs. The noise suppression characteristics of the proposed IEP-EBG structure were thoroughly analyzed using a dispersion diagram based on a full-wave simulation as well as an equivalent circuit model of a unit cell structure with a Floquet boundary condition. The proposed IEP-EBG structure has the advantages of substantial reductions in the low cut-off frequency of the first stopband as well as unit cell size when compared to a conventional mushroom-type EBG structure without the inductance-enhanced technique. The suppression of the PPW modes of the proposed IEP-EBG structure was verified using measurements of scattering parameters. In the measurements, the low and high cut-off frequencies of the first stopband of the IEP-EBG structure were found to be 1.55 GHz and 2.48 GHz, respectively, while those of the conventional mushroom type EBG structure were 3.52 GHz and 5.3 GHz. For the low cut-off frequency, a 56% reduction was achieved, resulting in substantial miniaturization suitable for compact packages and PCBs.
Study on the Incentives Mechanism for the Development of Distributed Photovoltaic Systems from a Long-Term Perspective
Authors: Sun Chenjun , Mi Zengqiang , Ren Hui , Wang Fei , Chen Jing , Watts David , Lu Jinling
Published: May 2018

Sharing the benefits of distribution systems from the integration of distributed photovoltaic systems (DGPVs) with investors is vital to the coordinated development of DGPVs and active distribution systems (ADN). The investment and development of DGPVs, incentive policies, and the development of distribution system interact, and the interactions vary with the changes in the on-grid capacity of DGPVs. In this paper, an event-driven co-simulation platform is built to simulate the abovementioned interaction among DGPVs, ADN, and incentive policy under a long-term time frame. The platform includes an investment model of DGPV investors and an ADN model with consideration of the growth of the ADN. On this platform, we study how multiple factors, including incentive system, global horizontal radiance (GHR), and cost, affect the investment and integration of DGPVs in the future 10 years. Simulation and analysis showed that investors’ decisions are more sensitive to variation in GHR and cost, followed by variation in tariff system, subsidy, and self-use ratio. Distribution subsidies have certain impact on the development of DGPV and could partially replace the national and provincial capacity and generation subsidies. When the on-grid capacity reaches a certain level, the distribution subsidy reaches a dynamic equilibrium.
Wind–PV-Based Hybrid DC Microgrid (DCMG) Development: An Experimental Investigation and Comparative Economic Analysis
Authors: Shaikh Pervez Hameed , Leghari Zohaib Hussain , Mirjat Nayyar Hussain , Shaikh Faheemullah , Solangi Asif Raza , Jan Tariqullah , Uqaili Muhammad Aslam
Published: May 2018

The cyclical nature and high investment costs of the wind and photovoltaic renewable energy sources are the two critical issues seeking attention for the use of such systems in backup or isolated applications. This paper aims to present the experimental and economic analysis of a wind–photovoltaic-based hybrid direct current microgrid (DCMG) system for backup power and off-grid isolated power generation system for emergency purposes. The two distributed generating units comprising photovoltaic panels and wind generator were designed and developed for the experimental study. A lead-acid battery is also added as an energy storage system to enhance the system supply. The electric load of this system comprise of 42 DC light emitting diode (LED) lamps of 12 Watt each and a 25 Watt DC fan. The charge controller provides the control and protection features for the designed system. The complete system design and fabrication of this system have been undertaken at Mehran University of Engineering & Technology (MUET, Jamshoro, Pakistan). The compatibility of the designed system has been analysed by comparing the Levelized Cost of Energy (LCOE) with a conventional gasoline generator system of the same capacity. The capital, running and lifetime costs of DCMG are found to be 1.29, 0.15 and 0.29 times those of the gasoline generator, respectively. Moreover, it is found that per unit cost of gasoline generator is $0.3 (i.e., PKR 31.4) which is almost 3.4 times higher than that of the hybrid DCMG system. The performance and cost evaluation of the designed system indicate its broad potential to be adopted for commercialisation to meet backup power and off-grid power requirements. This study concludes that proposed DCMG system is a not only low cost, but also a pollution-free alternative option compared to the existing traditional small gasoline generator system.
An Overall Bubble Diameter Model for the Flow Boiling and Numerical Analysis through Global Information Searching
Authors: Xu Zhexuan , Zhang Junhong , Lin Jiewei , Xu Tianshu , Wang Jingchao , Lin Zefeng
Published: May 2018

Bubble diameter is important for the three-dimensional nucleate boiling two-phase flow simulation. However, the bubble diameter is rarely considered as a variable because it is difficult to estimate. In this paper, a novel bubble diameter model is proposed for the boiling flow. The heat transfer growth, the breakup or coalescence of collision and the liquid impacting separation are considered as the factors affecting the bubble diameter, and three bubble diameter sub-models are developed to calculate the overall bubble diameter based on a departure diameter. In the model, the heat transfer growth is calculated after estimating the bubble location. The collision variation is deduced from the interfacial area concentration equation. The liquid impacting variation is calculated through phase interaction force and gas viscous force. The proposed model is conducted through global information searching in the flow boiling simulation and validated using the void fraction and temperature data from the literature. The effects of the heat transfer growth, the collision, and the separating volume on the bubble diameter are discussed.
Decomposing Air Pollutant Emissions in Asia: Determinants and Projections
Authors: Rafaj Peter , Amann Markus
Published: May 2018

High levels of air pollution pose an urgent social and public health challenge in many Asian regions. This study evaluates the role of key factors that determined the changes in emission levels in China, India and Japan over the past 25 years. While emissions of air pollutants have been declining in Japan since the 1990s, China and India have experienced a rapid growth in pollution levels in recent years. Around 2005, control measures for sulfur emissions started to deliver expected reductions in China, followed by cuts in nitrogen oxides ten years later. Despite recent policy interventions, growing emission trends in India persist. A decomposition analysis of emission-driving factors indicates that emission levels would have been at least two-times higher without the improvements in energy intensity and efficiency, combined with end-of-pipe measures. Due to the continuous reliance on fossil fuels, the abatement effect of a cleaner fuel mix was in most cases significantly smaller than other factors. A reassessment of emission projections developed in the past suggests a decisive impact of energy and environmental policies. It is expected that targeted legislative instruments will play a dominant role in achieving future air-quality goals in Asia.
Gender Differences in the Response to Decision Power and Responsibility—Framing Effects in a Dictator Game
Authors: Bruttel Lisa , Stolley Florian
Published: May 2018

This paper studies the effects of two different frames on decisions in a dictator game. Before making their allocation decision, dictators read a short text. Depending on the treatment, the text either emphasizes their decision power and freedom of choice or it stresses their responsibility for the receiver’s payoff. Including a control treatment without such a text, three treatments are conducted with a total of 207 dictators. Our results show a different reaction to these texts depending on the dictator’s gender. We find that only men react positively to a text that stresses their responsibility for the receiver, while only women seem to react positively to a text that emphasizes their decision power and freedom of choice.
Irreversible Swelling Behavior and Reversible Hysteresis in Chemically Crosslinked Poly(vinyl alcohol) Gels
Authors: Kamemaru Keiichiro , Usui Shintaro , Hirashima Yumiko , Suzuki Atsushi
Published: May 2018

We report the swelling properties of chemically crosslinked poly(vinyl alcohol) (PVA) gels with high degrees of polymerization and hydrolysis. Physical crosslinking by microcrystallites was introduced in this chemical PVA gel by a simple dehydration process. The equilibrium swelling ratio was measured in several mixed solvents, which comprised two-components: a good solvent (water or dimethyl sulfoxide (DMSO)), and a poor organic solvent for PVA. In the case of aqueous/organic solvent mixtures subjected to a multiple-sample test, the swelling ratio decreased continuously when the concentration of the organic solvent increased, reaching a collapsed state in the respective pure organic solvents. In the case of DMSO, starting from a swollen state, the swelling ratio rapidly decreased by between 15 and 50 mol % when the concentration of the organic compound increased in a single-sample test. To understand the hysteresis phenomenon, the swelling ratio was measured in a DMSO/acetone mixed solvent, starting from a collapsed state in acetone. The reversibility of swelling in response to successive concentration cycles between DMSO and acetone was examined. As a result, an irreversible swelling behavior was observed in the first cycle, and the swelling ratio in acetone after the first cycle became larger than the initial ratio. Subsequently, the swelling ratio changed reversibly, with a large hysteresis near a specific molar ratio of DMSO/acetone of 60/40. The microstructures were confirmed by Fourier transform infrared spectroscopy during the cycles. The irreversible swelling behavior and hysteresis are discussed in terms of the destruction and re-formation of additional physical crosslinking in the chemical PVA gels.
Genomic Differentiation during Speciation-with-Gene-Flow: Comparing Geographic and Host-Related Variation in Divergent Life History Adaptation in Rhagoletis pomonella
Authors: Doellman Meredith M. , Ragland Gregory J. , Hood Glen R. , Meyers Peter J. , Egan Scott P. , Powell Thomas H. Q. , Lazorchak Peter , Glover Mary M. , Tait Cheyenne , Schuler Hannes , Hahn Daniel A. , Berlocher Stewart H. , Smith James J. , Nosil Patrik , Feder Jeffrey L.
Published: May 2018

A major goal of evolutionary biology is to understand how variation within populations gets partitioned into differences between reproductively isolated species. Here, we examine the degree to which diapause life history timing, a critical adaptation promoting population divergence, explains geographic and host-related genetic variation in ancestral hawthorn and recently derived apple-infesting races of Rhagoletis pomonella. Our strategy involved combining experiments on two different aspects of diapause (initial diapause intensity and adult eclosion time) with a geographic survey of genomic variation across four sites where apple and hawthorn flies co-occur from north to south in the Midwestern USA. The results demonstrated that the majority of the genome showing significant geographic and host-related variation can be accounted for by initial diapause intensity and eclosion time. Local genomic differences between sympatric apple and hawthorn flies were subsumed within broader geographic clines; allele frequency differences within the races across the Midwest were two to three-fold greater than those between the races in sympatry. As a result, sympatric apple and hawthorn populations displayed more limited genomic clustering compared to geographic populations within the races. The findings suggest that with reduced gene flow and increased selection on diapause equivalent to that seen between geographic sites, the host races may be recognized as different genotypic entities in sympatry, and perhaps species, a hypothesis requiring future genomic analysis of related sibling species to R. pomonella to test. Our findings concerning the way selection and geography interplay could be of broad significance for many cases of earlier stages of divergence-with-gene flow, including (1) where only modest increases in geographic isolation and the strength of selection may greatly impact genetic coupling and (2) the dynamics of how spatial and temporal standing variation is extracted by selection to generate differences between new and discrete units of biodiversity.
Regulation Mediated by N-Acyl Homoserine Lactone Quorum Sensing Signals in the Rhizobium-Legume Symbiosis
Authors: Calatrava-Morales Nieves , McIntosh Matthew , Soto María J.
Published: May 2018

Soil-dwelling bacteria collectively referred to as rhizobia synthesize and perceive N-acyl-homoserine lactone (AHL) signals to regulate gene expression in a population density-dependent manner. AHL-mediated signaling in these bacteria regulates several functions which are important for the establishment of nitrogen-fixing symbiosis with legume plants. Moreover, rhizobial AHL act as interkingdom signals triggering plant responses that impact the plant-bacteria interaction. Both the regulatory mechanisms that control AHL synthesis in rhizobia and the set of bacterial genes and associated traits under quorum sensing (QS) control vary greatly among the rhizobial species. In this article, we focus on the well-known QS system of the alfalfa symbiont Sinorhizobium (Ensifer) meliloti. Bacterial genes, environmental factors and transcriptional and posttranscriptional regulatory mechanisms that control AHL production in this Rhizobium, as well as the effects of the signaling molecule on bacterial phenotypes and plant responses will be reviewed. Current knowledge of S. meliloti QS will be compared with that of other rhizobia. Finally, participation of the legume host in QS by interfering with rhizobial AHL perception through the production of molecular mimics will also be addressed.
The Guppy Sex Chromosome System and the Sexually Antagonistic Polymorphism Hypothesis for Y Chromosome Recombination Suppression
Authors: Charlesworth Deborah
Published: May 2018

Sex chromosomes regularly evolve suppressed recombination, distinguishing them from other chromosomes, and the reason for this has been debated for many years. It is now clear that non-recombining sex-linked regions have arisen in different ways in different organisms. A major hypothesis is that a sex-determining gene arises on a chromosome and that sexually antagonistic (SA) selection (sometimes called intra-locus sexual conflict) acting at a linked gene has led to the evolution of recombination suppression in the region, to reduce the frequency of low fitness recombinant genotypes produced. The sex chromosome system of the guppy (Poecilia reticulata) is often cited as supporting this hypothesis because SA selection has been demonstrated to act on male coloration in natural populations of this fish, and probably contributes to maintaining polymorphisms for the genetic factors involved. I review classical genetic and new molecular genetic results from the guppy, and other fish, including approaches for identifying the genome regions carrying sex-determining loci, and suggest that the guppy may exemplify a recently proposed route to sex chromosome evolution.
Functional Genomics Approaches to Studying Symbioses between Legumes and Nitrogen-Fixing Rhizobia
Authors: Lardi Martina , Pessi Gabriella
Published: May 2018

Biological nitrogen fixation gives legumes a pronounced growth advantage in nitrogen-deprived soils and is of considerable ecological and economic interest. In exchange for reduced atmospheric nitrogen, typically given to the plant in the form of amides or ureides, the legume provides nitrogen-fixing rhizobia with nutrients and highly specialised root structures called nodules. To elucidate the molecular basis underlying physiological adaptations on a genome-wide scale, functional genomics approaches, such as transcriptomics, proteomics, and metabolomics, have been used. This review presents an overview of the different functional genomics approaches that have been performed on rhizobial symbiosis, with a focus on studies investigating the molecular mechanisms used by the bacterial partner to interact with the legume. While rhizobia belonging to the alpha-proteobacterial group (alpha-rhizobia) have been well studied, few studies to date have investigated this process in beta-proteobacteria (beta-rhizobia).
GEV Parameter Estimation and Stationary vs. Non-Stationary Analysis of Extreme Rainfall in African Test Cities
Authors: De Paola Francesco , Giugni Maurizio , Pugliese Francesco , Annis Antonio , Nardi Fernando
Published: May 2018

Nowadays, increased flood risk is recognized as one of the most significant threats in most parts of the world, with recurring severe flooding events causing significant property and human life losses. This has entailed public debates on both the apparent increased frequency of extreme events and the perceived increases in rainfall intensities within climate changing scenarios. In this work, a stationary vs. Non-Stationary Analysis of annual extreme rainfall was performed with reference to the case studies of the African cities of Dar Es Salaam (TZ) and Addis Ababa (ET). For Dar Es Salaam (TZ) a dataset of 53 years (1958–2010) of maximum daily rainfall records (24 h) was analysed, whereas a 47-year time series (1964–2010) was taken into account for Addis Ababa (ET). Both gauge stations rainfall data were suitably fitted by Extreme Value Distribution (EVD) models. Inference models using the Maximum Likelihood Estimation (MLE) and the Bayesian approach were applied on EVD considering their impact on the shape parameter and the confidence interval width. A comparison between a Non-Stationary regression and a Stationary model was also performed. On this matter, the two time series did not show any Non-Stationary effect. The results achieved under the CLUVA (Climatic Change and Urban Vulnerability in Africa) EU project by the Euro-Mediterranean Centre for Climate Change (CMCC) (with 1 km downscaling) for the IPCC RCP8.5 climatological scenario were also applied to forecast the analysis until 2050 (93 years for Dar Es Salaam TZ and 86 years for Addis Ababa ET). Over the long term, the process seemed to be Non-Stationary for both series. Moreover, with reference to a 100-year return period, the IDF (Intensity-Duration-Frequency) curves of the two case-studies were estimated by applying the Maximum Likelihood Estimation (MLE) approach, as a function of confidence intervals of 2.5% and 97.5% quantiles. The results showed the dependence of Non-Stationary effects of climate change to be conveniently accounted for engineering design and management.
A Simple Alternative Method for Preservation of 2-Methylisoborneol in Water Samples
Authors: Fan Chun-Cheng , Chiu Yi-Ting , Lin Tsair-Fuh
Published: May 2018

2-Methylisoborneol (2-MIB) is one of the most commonly observed taste and odor (T&O) compounds present in drinking water sources. As it is biodegradable, a preservation agent, typically mercury chloride, is needed if the water is not analyzed right after sampling. Since mercury is a toxic metal, an alternative chemical that is cheaper and less toxic is desirable. In this study, two chemicals commonly used in water treatment processes, chlorine (as sodium hypochlorite) and KMnO4 (potassium permanganate), are studied to determine their feasibility as preservation agents for 2-MIB in water. Preservation experiments were first conducted in deionized water spiked with 2-MIB and with chlorine or permanganate at 4 and 25 °C. The results indicate that 2-MIB concentrations in the water samples spiked with both chemicals remained almost constant within 14 days for all the tested conditions, suggesting that oxidation and volatilization did not cause the loss of 2-MIB in the system. The experiments were further conducted for three different reservoir water samples with 30–60 ng/L of indulgent 2-MIB. The experimental results demonstrated that preservation with permanganate may have underestimated the 2-MIB concentration in the samples as a result of the formation of manganese dioxide particles in natural water and adsorption of 2-MIB onto the particles. Chlorine was demonstrated to be a good preservation agent for all three tested natural waters since oxidation of 2-MIB was negligible and biodegradation was inhibited. When the residual chlorine concentrations were controlled to be higher than 0.5 mg/L on the final day (day 14) of the experiments, the concentration reduction of 2-MIB became lower than 13% at both of the tested temperatures. The results demonstrated that sodium hypochlorite can be used as an alternative preservation agent for 2-MIB in water before analysis.
Quorum Sensing versus Quenching Bacterial Isolates Obtained from MBR Plants Treating Leachates from Municipal Solid Waste
Authors: Soler Albert , Arregui Lucía , Arroyo Miguel , Mendoza José Antonio , Muras Andrea , Álvarez Cristina , García-Vera Cristina , Marquina Domingo , Santos Antonio , Serrano Susana
Published: May 2018

Quorum sensing (QS) is a mechanism dependent on bacterial density. This coordinated process is mediated by the synthesis and the secretion of signal molecules, called autoinducers (AIs). N-acyl-homoserine lactones (AHLs) are the most common AIs that are used by Gram-negative bacteria and are involved in biofilm formation. Quorum Quenching (QQ) is the interference of QS by producing hydrolyzing enzymes, among other strategies. The main objective of the present study was to identify QS and QQ strains from MBR wastewater treatment plants. A total of 99 strains were isolated from two Spanish plants that were intended to treat leachate from municipal solid waste. Five AHL producers were detected using AHL biosensor strains (Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NT1). Fifteen strains of seventy-one Gram-positive were capable of eliminating or reducing at least one AHL activity. The analysis of 16S rRNA gene sequence showed the importance of the Pseudomonas genus in the production of biofilms and the relevance of the genus Bacillus in the disruption of the QS mechanism, in which the potential activity of lactonase or acylase enzymes was investigated with the aim to contribute to solve biofouling problems and to increase the useful lifespan of membranes.
Smoking Topography among Korean Smokers: Intensive Smoking Behavior with Larger Puff Volume and Shorter Interpuff Interval
Authors: Kim Sungroul , Yu Sol
Published: May 2018

The difference of smoker’s topography has been found to be a function many factors, including sex, personality, nicotine yield, cigarette type (i.e., flavored versus non-flavored) and ethnicity. We evaluated the puffing behaviors of Korean smokers and its association with smoking-related biomarker levels. A sample of 300 participants was randomly recruited from metropolitan areas in South Korea. Topography measures during a 24-hour period were obtained using a CReSS pocket device. Korean male smokers smoked two puffs less per cigarette compared to female smokers (15.0 (13.0–19.0) vs. 17.5 (15.0–21.0) as the median (Interquartile range)), but had a significantly larger puff volume (62.7 (52.7–75.5) mL vs. 53.5 (42.0–64.2) mL); p = 0.012). The interpuff interval was similar between men and women (8.9 (6.5–11.2) s vs. 8.3 (6.2–11.0) s; p = 0.122) but much shorter than other study results. A dose-response association (p = 0.0011) was observed between daily total puff volumes and urinary cotinine concentrations, after controlling for sex, age, household income level and nicotine addiction level. An understanding of the difference of topography measures, particularly the larger puff volume and shorter interpuff interval of Korean smokers, may help to overcome a potential underestimation of internal doses of hazardous byproducts of smoking.
Measuring Cortisol in the Classroom with School-Aged Children—A Systematic Review and Recommendations
Authors: Dimolareva Mirena , Gee Nancy R. , Pfeffer Karen , Maréchal Laëtitia , Pennington Kyla , Meints Kerstin
Published: May 2018

The collection of salivary cortisol has been chosen as one of the least intrusive, easiest to collect, analyze, and store methods of obtaining information on physiological changes. It is, however, not clear what the best practice is when collecting salivary cortisol from children within the school setting. The aim of this systematic review is to evaluate the feasibility of cortisol collection in schools for future research and to make recommendations for best practice. The review included 25 peer-reviewed articles from seven databases. The hypotheses of the included studies vary, but they all use cortisol as a diurnal, baseline, or acute measure, or to measure the effect of an intervention. Two methods of salivary cortisol collection were preferred by most of the research, i.e., passive drool or cotton Salivettes. The review has concluded that cortisol is a physiological marker that can be successfully measured in school-based research. However, there are discrepancies across studies when evaluating the collection guidelines, protocols, and instructions to participants as well as transparency of the success rate of obtaining all samples. Recommendations are made for future research to address and avoid such discrepancies and improve cross-study comparisons by implementing standard protocol guidelines.
Profitability Determinants of Financial Institutions: Evidence from Banks in Pakistan
Authors: Yao Hongxing , Haris Muhammad , Tariq Gulzara
Published: May 2018

The aim of this study was to analyze the impact of bank-specific, industry-specific and macroeconomic variables on the profitability of banks in Pakistan. This study applied the two-step generalized method of momentum (GMM) system estimator on an unbalanced dynamic panel of 28 banks over the latest period 2007–2016. The robust results reveal that the bank’s profitability in Pakistan is explained by size, higher solvency, financial structure, operating cost, labor productivity, market power, and economic growth. We also found an inverted U-shape relationship between banks size and profitability. Herfindahl–Hirschman Index (HHI) was applied to evaluate the impact of market power and found results in support of Structure Conduct Hypothesis. On the other hand, credit quality, operational efficiency, banking sector development, inflation, and industry concentration are found to be negatively and significantly related to the profitability of banks. Further, this study found lower profitability of banks during the government transition. The Mean comparison of profitability indicates that specialized banks (SB) in Pakistan are generating higher net interest margin (NIM) than all commercial banks (ACB). However, the empirical results of this study are robust and consistent with previous literature.
Multi-Factor Asset-Pricing Models under Markov Regime Switches: Evidence from the Chinese Stock Market
Authors: Chen Jieting , Kawaguchi Yuichiro
Published: May 2018

This paper proposes a Markov regime-switching asset-pricing model and investigates the asymmetric risk-return relationship under different regimes for the Chinese stock market. It was found that the Chinese stock market has two significant regimes: a persistent bear market and a bull market. In regime 1, the risk premiums on common risk factors were relatively higher and consistent with the hypothesis that investors require more compensation for taking the same amount of risks in a bear regime when there is a higher risk-aversion level. Moreover, return dispersions among the Fama–French 25 portfolios were captured by the beta patterns from our proposed Markov regime-switching Fama–French three-factor model, implying that a positive risk-return relationship holds in regime 1. On the contrary, in regime 2, when lower risk premiums could be observed, portfolios with a big size or low book-to-market ratio undertook higher risk loadings, implying that the stocks that used to be known as “good” stocks were much riskier in a bull market. Thus, a risk-return relationship followed other patterns in this period.
A Formalized 3D Geovisualization Illustrated to Selectivity Purpose of Virtual 3D City Model
Authors: Neuville Romain , Pouliot Jacynthe , Poux Florent , De Rudder Laurent , Billen Roland
Published: May 2018

Virtual 3D city models act as valuable central information hubs supporting many aspects of cities, from management to planning and simulation. However, we noted that 3D city models are still underexploited and believe that this is partly due to inefficient visual communication channels across 3D model producers and the end-user. With the development of a formalized 3D geovisualization approach, this paper aims to support and make the visual identification and recognition of specific objects in the 3D models more efficient and useful. The foundation of the proposed solution is a knowledge network of the visualization of 3D geospatial data that gathers and links mapping and rendering techniques. To formalize this knowledge base and make it usable as a decision-making system for the selection of styles, second-order logic is used. It provides a first set of efficient graphic design guidelines, avoiding the creation of graphical conflicts and thus improving visual communication. An interactive tool is implemented and lays the foundation for a suitable solution for assisting the visualization process of 3D geospatial models within CAD and GIS-oriented software. Ultimately, we propose an extension to OGC Symbology Encoding in order to provide suitable graphic design guidelines to web mapping services.
Melatonin Analogue Antiproliferative and Cytotoxic Effects on Human Prostate Cancer Cells
Authors: Calastretti Angela , Gatti Giuliana , Lucini Valeria , Dugnani Silvana , Canti Gianfranco , Scaglione Francesco , Bevilacqua Annamaria
Published: May 2018

Melatonin has been indicated as a possible oncostatic agent in different types of cancer, its antiproliferative role being demonstrated in several in vitro and in vivo experimental models of tumors. Specifically, melatonin was proven to inhibit cell growth of both androgen-dependent and independent prostate cancer cells, through various mechanisms. A number of melatonin derivatives have been developed and tested for their role in the prevention and treatment of neoplastic diseases. We recently proved the in vitro and in vivo anticancer activity of UCM 1037, a newly-synthetized melatonin analogue, on melanoma and breast cancer cells. In this study we evaluated UCM 1037 effects on cell proliferation, cell cycle distribution, and cytotoxicity in LNCaP, PC3, DU145, and 22Rv1 prostate cancer cells. We demonstrated significant dose- and time-dependent UCM 1037 antiproliferative effects in androgen-sensitive LNCaP and 22Rv1 cells. Data from flow cytometric studies suggest that UCM 1037 is highly cytotoxic in androgen-sensitive prostate cancer cells, although no substantial increase in the apoptotic cell fraction has been observed. UCM 1037 cytotoxic effects were much less evident in androgen-insensitive PC3 and DU145 cells. Experiments performed to gain insights into the possible mechanism of action of the melatonin derivative revealed that UCM 1037 down-regulates androgen receptor levels and Akt activation in LNCaP and 22Rv1 cells.
Pharmacological Strategies for Manipulating Plant Ca2+ Signalling
Authors: De Vriese Kjell , Costa Alex , Beeckman Tom , Vanneste Steffen
Published: May 2018

Calcium is one of the most pleiotropic second messengers in all living organisms. However, signalling specificity is encoded via spatio-temporally regulated signatures that act with surgical precision to elicit highly specific cellular responses. How this is brought about remains a big challenge in the plant field, in part due to a lack of specific tools to manipulate/interrogate the plant Ca2+ toolkit. In many cases, researchers resort to tools that were optimized in animal cells. However, the obviously large evolutionary distance between plants and animals implies that there is a good chance observed effects may not be specific to the intended plant target. Here, we provide an overview of pharmacological strategies that are commonly used to activate or inhibit plant Ca2+ signalling. We focus on highlighting modes of action where possible, and warn for potential pitfalls. Together, this review aims at guiding plant researchers through the Ca2+ pharmacology swamp.
GDF11 Modulates Ca2+-Dependent Smad2/3 Signaling to Prevent Cardiomyocyte Hypertrophy
Authors: Duran Javier , Troncoso Mayarling Francisca , Lagos Daniel , Ramos Sebastian , Marin Gabriel , Estrada Manuel
Published: May 2018

Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β family, has been shown to act as a negative regulator in cardiac hypertrophy. Ca2+ signaling modulates cardiomyocyte growth; however, the role of Ca2+-dependent mechanisms in mediating the effects of GDF11 remains elusive. Here, we found that GDF11 induced intracellular Ca2+ increases in neonatal rat cardiomyocytes and that this response was blocked by chelating the intracellular Ca2+ with BAPTA-AM or by pretreatment with inhibitors of the inositol 1,4,5-trisphosphate (IP3) pathway. Moreover, GDF11 increased the phosphorylation levels and luciferase activity of Smad2/3 in a concentration-dependent manner, and the inhibition of IP3-dependent Ca2+ release abolished GDF11-induced Smad2/3 activity. To assess whether GDF11 exerted antihypertrophic effects by modulating Ca2+ signaling, cardiomyocytes were exposed to hypertrophic agents (100 nM testosterone or 50 μM phenylephrine) for 24 h. Both treatments increased cardiomyocyte size and [3H]-leucine incorporation, and these responses were significantly blunted by pretreatment with GDF11 over 24 h. Moreover, downregulation of Smad2 and Smad3 with siRNA was accompanied by inhibition of the antihypertrophic effects of GDF11. These results suggest that GDF11 modulates Ca2+ signaling and the Smad2/3 pathway to prevent cardiomyocyte hypertrophy.
Clinical and Molecular Aspects of Vitiligo Treatments
Authors: Bishnoi Anuradha , Parsad Davinder
Published: May 2018

Vitiligo is an asymptomatic but cosmetically disfiguring disorder that results in the formation of depigmented patches on skin and/or mucosae. Vitiligo can be segmental or non-segmental depending upon the morphology of the clinical involvement. It can also be classified as progressing or stable based on the activity of the disease. Further, the extent of involvement can be limited (localized disease) or extensive (generalized disease). The treatment of vitiligo therefore depends on the clinical classification/characteristics of the disease and usually comprises of 2 strategies. The first involves arresting the progression of active disease (to provide stability) in order to limit the area involved by depigmentation. The second strategy aims at repigmentation of the depigmented area. It is also important to maintain the disease in a stable phase and to prevent relapse. Accordingly, a holistic treatment approach for vitiligo should be individualistic and should take care of all these considerations. In this review, we shall discuss the vitiligo treatments and their important clinical and molecular aspects.
Identification of Novel Somatic TP53 Mutations in Patients with High-Grade Serous Ovarian Cancer (HGSOC) Using Next-Generation Sequencing (NGS)
Authors: Garziera Marica , Cecchin Erika , Canzonieri Vincenzo , Sorio Roberto , Giorda Giorgio , Scalone Simona , De Mattia Elena , Roncato Rossana , Gagno Sara , Poletto Elena , Romanato Loredana , Sartor Franca , Polesel Jerry , Toffoli Giuseppe
Published: May 2018

Somatic mutations in TP53 are a hallmark of high-grade serous ovarian cancer (HGSOC), although their prognostic and predictive value as markers is not well defined. Next-generation sequencing (NGS) can identify novel mutations with high sensitivity, that may be repurposed as potential druggable anti-cancer targets and aid in therapeutic decisions. Here, a commercial NGS cancer panel comprising 26 genes, including TP53, was used to identify new genetic markers of platinum resistance and patient prognosis in a retrospective set of patients diagnosed with epithelial ovarian cancer. Six novel TP53 somatic mutations in untreated tumors from six distinct patients diagnosed with HGSOC were identified: TP53 c.728_739delTGGGCGGCATGA (p.Met243_Met247del, in-frame insertion or deletion (INDEL); TP53 c.795_809delGGGACGGAACAGCTT (p.Gly266_Phe270del, in-frame INDEL); TP53 c.826_827GC>AT (p.Ala276Ile, missense); TP53 c.1022insT (p.Arg342Profs*5, frameshift INDEL); TP53 c.1180delT (p.Ter394Aspfs*28, frameshift INDEL); and TP53 c.573insT (p.Gln192Serfs*17, frameshift INDEL). Novel TP53 variants were validated by classical sequencing methods and their impact on protein expression in tumors explored by immunohistochemistry. Further insights into the potential functional effect of the mutations were obtained by different in silico approaches, bioinformatics tools, and structural modeling. This discovery of previously unreported TP53 somatic mutations provides an opportunity to translate NGS technology into personalized medicine and identify new potential targets for therapeutic applications.
Application of a Novel Anti-Adhesive Membrane, E8002, in a Rat Laminectomy Model
Authors: Kikuchi Kiyoshi , Setoyama Kentaro , Terashi Takuto , Sumizono Megumi , Tancharoen Salunya , Otsuka Shotaro , Takada Seiya , Nakanishi Kazuki , Ueda Koki , Sakakima Harutoshi , Kawahara Ko-ichi , Maruyama Ikuro , Hattori Gohsuke , Morioka Motohiro , Tanaka Eiichiro , Uchikado Hisaaki
Published: May 2018

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin–eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.
Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-like β-Sandwich Proteins
Authors: Sun Yunxiang , Ding Feng , Ming Dengming
Published: May 2018

Nonnative interactions cause energetic frustrations in protein folding and were found to dominate key events in folding intermediates. However, systematically characterizing energetic frustrations that are caused by nonnative intra-residue interactions at residual resolution is still lacking. Recently, we studied the folding of a set of homologous all-α proteins and found that nonnative-contact-based energetic frustrations are highly correlated to topology of the protein native-contact network. Here, we studied the folding of nine homologous immunoglobulin-like (Ig-like) β-sandwich proteins, and examined nonnative-contact-based energetic frustrations Gō-like model. Our calculations showed that nonnative-interaction-based energetic frustrations in β-sandwich proteins are much more complicated than those in all- α proteins, and they exhibit highly heterogeneous effects on the folding of secondary structures. Further, the nonnative interactions introduced distinct correlations in the folding of different folding-patches of β-sandwich proteins. Taken together, a strong interplay might exist between nonnative-interaction energetic frustrations and the protein native-contact networks, which ensures that β-sandwich domains adopt a common folding mechanism.
Serine Protease Inhibitor SERPINE2 Reversibly Modulates Murine Sperm Capacitation
Authors: Li Sheng-Hsiang , Hwu Yuh-Ming , Lu Chung-Hao , Lin Ming-Huei , Yeh Ling-Yu , Lee Robert Kuo-Kuang
Published: May 2018

SERPINE2 (serpin peptidase inhibitor, clade E, member 2), predominantly expressed in the seminal vesicle, can inhibit murine sperm capacitation, suggesting its role as a sperm decapacitation factor (DF). A characteristic of DF is its ability to reverse the capacitation process. Here, we investigated whether SERPINE2 can reversibly modulate sperm capacitation. Immunocytochemical staining revealed that SERPINE2 was bound onto both capacitated and uncapacitated sperm. It reversed the increase in BSA-induced sperm protein tyrosine phosphorylation levels. The effective dose and incubation time were found to be >0.1 mg/mL and >60 min, respectively. Calcium ion levels in the capacitated sperm were reduced to a level similar to that in uncapacitated sperm after 90 min of incubation with SERPINE2. In addition, the acrosome reaction of capacitated sperm was inhibited after 90 min of incubation with SERPINE2. Oviductal sperm was readily induced to undergo the acrosome reaction using the A23187 ionophore; however, the acrosome reaction was significantly reduced after incubation with SERPINE2 for 60 and 120 min. These findings suggested that SERPINE2 prevented as well as reversed sperm capacitation in vitro. It also prevented the acrosome reaction in in vivo-capacitated sperm isolated from the oviduct. Thus, SERPINE2 could reversibly modulate murine sperm capacitation.