bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling and Design of Real-Time Energy Management Systems for Fuel Cell/Battery Electric Vehicles
Authors: Serpi Alessandro , Porru Mario
Published: November 2019

Modelling and design of real-time energy management systems for optimising the operating costs of a fuel cell/battery electric vehicle are presented in this paper. The proposed energy management system consists of optimally sharing the propulsion power demand between the fuel cell and battery by enabling them to support each other for operating cost minimisation. The optimisation is achieved through real-time minimisation of a cost function, which accounts for fuel cell and battery degradation, hydrogen consumption and charge sustaining costs. A detailed analysis of each term of the overall cost function is performed and presented, which enables the development of a real-time, advanced energy management system for improving a previously presented simplified version using more accurate modelling and by considering cost function minimisation over a given time horizon. The performance of the proposed advanced energy management system are verified through numerical simulations over different driving cycles; particularly, simulations were performed in MATLAB-Simulink by considering a hysteresis-based energy management system and both simplified and advanced versions of the proposed energy management system for comparison.
Long-Term Projection of Renewable Energy Technology Diffusion
Authors: Skoczkowski Tadeusz , Bielecki Sławomir , Wojtyńska Joanna
Published: November 2019

The EU aims at increasing the use of renewable energy sources (RES), mainly solar-photovoltaic (PV) and wind technologies. Projecting the future, in this respect, requires a long-term energy modeling which includes a rate of diffusion of novel technologies into the market and the prediction of their costs. The aim of this article has been to project the pace at which RES technologies diffused in the past or may diffuse in the future across the power sector. This analysis of the dynamics of technologies historically as well as in modeling, roadmaps and scenarios consists in a consistent analysis of the main parameters of the dynamics (pace of diffusion and extent of diffusion in particular markets). Some scenarios (REMIND, WITCH, WEO, PRIMES) of the development of the selected power generation technologies in the EU till 2050 are compared. Depending on the data available, the learning curves describing the expected development of PV and wind technologies till 2100 have been modeled. The learning curves have been presented as a unit cost of the power versus cumulative installed capacity (market size). As the production capacity increases, the cost per unit is reduced thanks to learning how to streamline the manufacturing process. Complimentary to these learning curves, logistic S-shape functions have been used to describe technology diffusion. PV and wind generation technologies for the EU have been estimated in time domain till 2100. The doubts whether learning curves are a proper method of representing technological change due to various uncertainties have been discussed. A critical analysis of effects of the commonly applied models for a long-term energy projection (REMIND, WITCH) use has been conducted. It has been observed that for the EU the analyzed models, despite differences in the target saturation levels, predict stagnation in the development of PV and wind technologies from around 2040. Key results of the analysis are new insights into the plausibility of future deployment scenarios in different sectors, informed by the analysis of historical dynamics of technology diffusion, using to the extent possible consistent metrics.
Development and Numerical Performance Analysis of a Pump Directly Driven by a Hydrokinetic Turbine
Authors: Zhou Daqing , Chen Huixiang , Zheng Yuan , Kan Kan , Yu An , Binama Maxime
Published: November 2019

Marine and hydrokinetics (MHK) represent an emerging industry with hundreds of potentially viable technologies, such as potential extractable energy from plain area rivers where the water level differences are very small and the traditional water turbine pump (WTP) cannot be used. A suitable WTP, composed of a tubular turbine directly driving a centrifugal pump, was designed and developed based on computational fluid dynamics (CFD) and model tests. Two general design schemes of such river-current (RC)-driven WTP are presented here, obtaining the desired operating parameters of discharge and pump head. A CFD analysis of Scheme B, which employs a radial outlet, allowing additional degrees of freedom for the dimensions of the centrifugal pump, was carried out and verified experimentally by model tests. The minimum deviation of pump head is within ±5%, and the trend of other working conditions is consistent, so the results of the numerical simulation and model tests show good agreement, demonstrating the feasibility of the CFD method for practical applications. Then, using the CFD method, the optimum rotational speed for the turbine was determined, and the turbine draft tube was improved further. With a turbine runner diameter of 0.5 m, the results show best performance at n = 350 r/min. The straight conical draft tube was changed to an elbow draft tube with multiple exits. Additionally, four different cross-sectional shapes were designed for the pump volute, and their effects on the performance of the WTP were analyzed. Finally, the round shape was selected, because of its best performance. The turbine unit has the highest efficiency of 81.2%, at an inlet velocity v = 2.4 m/s, while the pump exhibits the best efficiency of 90.2% at the design discharge and head of 30 l/s and 4.45 m respectively. Overall, the RC-driven WTP makes good use of the kinetic energy of the river current as a power source, solving the inapplicability of traditional WTP in plain areas.
Evaluation of the Mechanical Instability of Mining Roadway Overburden: Research and Applications
Authors: Jia Housheng , Pan Kun , Liu Shaowei , Peng Bo , Fan Kai
Published: November 2019

Under the superposed action of the primary rock stress and the mining stress, the compound roof of a roadway will have irregular plastic failure zone with greater depth, resulting in a wide range of non-uniform deformations and roof failures. Mastering the deformation and failure characteristics of this roof is essentially to recognize the development of the plastic zone of a compound roof. In this paper, the on-site roof detection method is mainly adopted to arrange a large number of boreholes for visualization and the deep displacement monitoring with the high-density points. Combined with numerical simulations, the rupture development characteristics and deformation mechanisms of the compound roof are revealed. The results show that the magnitude and direction of the principal stress of surrounding rock in a mining roadway are constantly changing, and the penetrating phenomenon will occur during the plastic zone expansion process. The order of the compound roof rupture as follows: shallow strata plastic failure, deep strata penetrating plastic failure and middle strata rupture. Severe roof deformation is mainly caused by plastic failure, and the strong deformation pressure caused by deep strata penetration plastic failure can easily lead to tensile failure and rupture in the middle strata. According to the plastic zone penetration development of the compound roof, the hierarchical support design led by the long-extension bolt is carried out on the test roadway. The monitoring results show that the roof is controlled well. The research results can provide a reference for the control of compound roofs in mining roadways.
Frequency Adaptive Current Control Scheme for Grid-connected Inverter without Grid Voltage Sensors Based on Gradient Steepest Descent Method
Authors: Tran Thuy Vi , Kim Myungbok , Kim Kyeong-Hwa
Published: November 2019

This paper presents a frequency adaptive grid voltage sensorless control scheme of a grid-connected inductive–capacitive–inductive (LCL)-filtered inverter, which is based on an adaptive current controller and a grid voltage observer. The frequency adaptive current controller is constructed by a full-state feedback regulator with the augmentation of multiple control terms to restrain not only the inherent resonance phenomenon that is caused by LCL filter, but also current harmonic distortions from an adverse grid environment. The number of required sensing devices is minimized in the proposed scheme by means of a discrete-time current-type observer, which estimates the system state variables, and gradient-method-based observers, which estimate the grid voltages and frequency simultaneously at different grid conditions. The estimated grid frequency is utilized in the current control loop to provide high-quality grid-injected currents, even under harmonic distortions and the frequency variation of grid voltages. As a result, the grid frequency adaptive control performance as well as the robustness against distorted grid voltages can be realized. Finally, an inverter synchronization task without using grid voltage sensors is accomplished by a fundamental grid voltage filter and a phase-locked loop to detect the actual grid phase angle. The stability and convergence performance of the proposed observers have been studied by means of the Lyapunov theory to ensure a high accuracy tracking performance of estimated variables. Simulation and experimental results are presented to validate the feasibility and the effectiveness of the proposed control approach.
Energy Performance Investigation of a Direct Expansion Ventilation Cooling System with a Heat Wheel
Authors: Kassai Miklos
Published: November 2019

Climate change is continuously bringing hotter summers and because of this fact, the use of air-conditioning systems is also extending in European countries. To reduce the energy demand and consumption of these systems, it is particularly significant to identify further technical solutions for direct cooling. In this research work, a field study is carried out on the cooling energy performance of an existing, operating ventilation system placed on the flat roof of a shopping center, located in the city of Eger in Hungary. The running system supplies cooled air to the back office and storage area of a shop and includes an air-to-air rotary heat wheel, a mixing box element, and a direct expansion cooling coil connected to a variable refrigerant volume outdoor unit. The objective of the study was to investigate the thermal behavior of each component separately, in order to make clear scientific conclusions from the point of view of energy consumption. Moreover, the carbon dioxide cross-contamination in the heat wheel was also analyzed, which is the major drawback of this type heat recovery unit. To achieve this, an electricity energy meter was installed in the outdoor unit and temperature, humidity, air velocity, and carbon dioxide sensors were placed in the inlet and outlet section of each element that has an effect on the cooling process. To provide continuous data recording and remote monitoring of air handling parameters and energy consumption of the system, a network monitor interface was developed by building management system-based software. The energy impact of the heat wheel resulted in a 624 kWh energy saving and 25.1% energy saving rate for the electric energy consumption of the outdoor unit during the whole cooling period, compared to the system without heat wheel operation. The scale of CO2 cross-contamination in the heat wheel was evaluated as an average value of 16.4%, considering the whole cooling season.
Experimental Study of Sand Production during Depressurization Exploitation in Hydrate Silty-Clay Sediments
Authors: Lu Jingsheng , Li Dongliang , He Yong , Shi Lingli , Liang Deqing , Xiong Youming
Published: November 2019

Silty-clay reservoirs are a weak point in sand production and sand control studies due to their low economy. However, China’s marine natural gas hydrates (NGH) mostly exist in silty-clay sediments, which restrict the sustainable and efficient development of NGH. In order to study the sand production of hydrate silty-clay sediments, hydrate production experiments in vertical wells and horizontal wells were carried out using a self-developed hydrate sand production and sand control simulation device. The results showed a great difference between the hydrate silty-clay sediments and hydrate sand sediments. The significant differences in production pressure and production temperature between the different layers indicated the low permeability and low heterogeneity of the hydrate silty-clay sediments. The sliding settlement of the overall depression in the horizontal well and overall subsidence in the vertical well of the hydrate silty-clay reservoir would easily lead to silty-clay flow and large-scale sand production. When water rates decreased, the property of “silty-clay sediment filtration and wall building” was found, which formed a “mud cake” around the wellbore. The good strength of adhesion and fracture permeability of the “mud cake” provided ideas for reservoir reformation. This study further discusses sand production and sediment reformation in hydrate silty-clay sediments.
A New Simplified Five-Parameter Estimation Method for Single-Diode Model of Photovoltaic Panels
Authors: Stornelli Vincenzo , Muttillo Mirco , de Rubeis Tullio , Nardi Iole
Published: November 2019

This work proposes a new simplified five-parameter estimation method for a single-diode model of photovoltaic panels. The method, based on an iterative algorithm, is able to estimate the parameter of the electrical single-diode model from the panel’s datasheet. Two iterative steps are used to estimate the five parameters starting from data provided by the manufacturer (nameplate values or I–V curves). The first step permits finding the optimal value of the diode ideality factor A, and the second step allows the calculation of the Rp value to improve the accuracy. A model that takes into account variations in temperature and solar irradiance has been used to validate the behavior of the output parameters. Compared to other estimation work, the proposed method shows the best result in the standard test condition (STC) and with a variable solar irradiance. Indeed, the optimization of the A, Rs, and Rp parameters allows guaranteeing the minimum error between I–V curves obtained from method and datasheet.
Optimization of a Cascaded H-Bridge Inverter for Electric Vehicle Applications Including Cost Consideration
Authors: Roemer Felix , Ahmad Massab , Chang Fengqi , Lienkamp Markus
Published: November 2019

This paper presents a method to find the optimal configuration for an electric vehicle energy storage system using a cascaded H-bridge (CHB) inverter. CHB multilevel inverters enable a better utilization of the battery pack, because cells/modules with manufacturing tolerances in terms of capacity can be selectively discharged instead of being passively balanced by discharging them over resistors. The balancing algorithms have been investigated in many studies for the CHB topology. However, it has not yet been investigated to which extend a conventional pack can be modularized in a CHB configuration. Therefore, this paper explores different configurations by simulating different switch models, switch configurations, and number of levels for a CHB inverter along with a reference load model to find the optimal design of the system. The configuration is also considered from an economically point of view, as the most efficient solution might not be cost-effective to be installed in a common production vehicle. It is found that four modules per phase give the best compromise between efficiency and costs. Paralleling smaller switches should be preferred over the usage of fewer, larger switches. Moreover, selecting specific existing components results in higher savings compared to theoretical optimal components.
Influencers on Thyroid Cancer Onset: Molecular Genetic Basis
Authors: Luzón-Toro Berta , Fernández Raquel , Villalba-Benito Leticia , Torroglosa Ana , Antiñolo Guillermo , Borrego Salud
Published: November 2019

Thyroid cancer, a cancerous tumor or growth located within the thyroid gland, is the most common endocrine cancer. It is one of the few cancers whereby incidence rates have increased in recent years. It occurs in all age groups, from children through to seniors. Most studies are focused on dissecting its genetic basis, since our current knowledge of the genetic background of the different forms of thyroid cancer is far from complete, which poses a challenge for diagnosis and prognosis of the disease. In this review, we describe prevailing advances and update our understanding of the molecular genetics of thyroid cancer, focusing on the main genes related with the pathology, including the different noncoding RNAs associated with the disease.
Oral Appliances in Obstructive Sleep Apnea
Authors: Dieltjens Marijke , Vanderveken Olivier M.
Published: November 2019

Oral appliance therapy is increasingly prescribed as a non-invasive treatment option for patients diagnosed with obstructive sleep apnea. The custom-made titratable mandibular advancement devices (MAD) are the recommended type of oral appliances. Mandibular advancement devices are efficacious in reducing the severity of obstructive sleep apnea, however, only to a lesser extent than standard therapy using continuous positive airway pressure (CPAP). Although oral appliance therapy is known to reduce the severity of obstructive sleep apnea in most of the patients, one out of three patients still show negligible improvement under MAD therapy. Therefore, the selection of the appropriate candidates for this therapy is imperative and several upfront prediction tools are described. Overall, the health outcome of mandibular advancement device therapy is similar to that of CPAP, probably due to the inferior compliance of CPAP compared to MAD therapy, resulting in similar clinical effectiveness.
Communication and Community Involvement to Support Risk Governance
Authors: Cori Liliana , Bianchi Fabrizio , Sprovieri Mario , Cuttitta Angela , Ruggieri Silvia , Alessi Anna Lisa , Biondo Girolama , Gorini Francesca
Published: November 2019

In past years, communication activities have become increasingly important in the environment and health domain, considering the concurrent developments of social media and scientific citizenship that contributed changes in legislation and culture. Communication is particularly crucial where an environmental hazard is present, as in the case of high risk environmental and health risk areas. The project “International Center of Advanced Study in Environment, Ecosystem and Human Health” (CISAS), carried out by the Italian National Research Council, covers multiple research activities, from ecology to biology and medical sciences, from epidemiology to social sciences and communication. Three different studies based on human biomonitoring and a birth cohort study are currently in progress in the project locations, together with studies on the environmental fate of pollutants. A clear, accurate and respectful communication of study protocols and results represents a priority to produce comprehensible information available for policy makers, citizens, and stakeholders. This paper describes the multiple external and internal communication activities planned in the framework of the CISAS project as an example of promotion of knowledge in the society at large and improvement of risk management in the environmental health domain.
The Nutritional Behaviour of Pregnant Women in Poland
Authors: Ługowska Katarzyna , Kolanowski Wojciech
Published: November 2019

A woman’s diet during pregnancy can significantly affect her health, as well as her child’s future development and well-being. Unfortunately, many pregnant women do not follow the recommended nutritional guidelines. The reason could be that they have insufficient knowledge about nutritional best practice. Accordingly, the purpose of this study is to investigate the nutritional behaviour of pregnant women in Poland. The research was conducted using a questionnaire to survey a sample of N = 815 pregnant women in first pregnancy. Among the findings were that the subjects ate an excessive amount of sweets, and white bread, and consumed insufficient quantities of fish, milk and fermented milk drinks. Subjects chose white bread more often than wholemeal bread, and fruit rather than vegetables. The study showed that the nutritional behaviour of pregnant women was characterised by many bad practices.
Intrapreneurial Self-Capital Mediates the Connectedness to Nature Effect on Well-Being at Work
Authors: Di Fabio Annamaria , Palazzeschi Letizia , Duradoni Mirko
Published: November 2019

Researchers are being called upon to find and explore viable solutions to protect the environment and promote health in the new digital era of the 21st century, since the rapid changes transpiring within our technological societies may be detrimental to workers but also offer opportunities for growth. The concept of connectedness to nature, on the one hand, is a proxy for important environmentally protective and responsible behaviors; on the other, it has been studied in relation to people’s well-being. To promote health, it is crucial to act from a primary prevention perspective, which is focused on finding variables that can be increased through specific training. In this framework, intrapreneurial self-capital (ISC) appears to be related both to people’s connectedness to nature and their well-being. This study analyzes exploratively the relationship between connectedness to nature, ISC, and well-being at work, since these variables have never been studied together. A mediation model is tested to assess whether ISC could mediate the relationship between connectedness to nature and workers’ well-being. The mediation analysis highlights that ISC, as a core of preventive resources, potentially sustains the effect of feeling connected to nature on well-being at work. Thus, interventions aimed at increasing and acquiring preventive resources, such as ISC, could be beneficial in protecting the environment and in promoting health among workers.
Comparison of Word Embeddings for Extraction from Medical Records
Authors: Dudchenko Aleksei , Kopanitsa Georgy
Published: November 2019

This paper is an extension of the work originally presented in the 16th International Conference on Wearable, Micro and Nano Technologies for Personalized Health. Despite using electronic medical records, free narrative text is still widely used for medical records. To make data from texts available for decision support systems, supervised machine learning algorithms might be successfully applied. In this work, we developed and compared a prototype of a medical data extraction system based on different artificial neural network architectures to process free medical texts in the Russian language. Three classifiers were applied to extract entities from snippets of text. Multi-layer perceptron (MLP) and convolutional neural network (CNN) classifiers showed similar results to all three embedding models. MLP exceeded convolutional network on pipelines that used the embedding model trained on medical records with preliminary lemmatization. Nevertheless, the highest F-score was achieved by CNN. CNN slightly exceeded MLP when the biggest word2vec model was applied (F-score 0.9763).
Persistent Organic Pollutants in Food: Contamination Sources, Health Effects and Detection Methods
Authors: Guo Wenjing , Pan Bohu , Sakkiah Sugunadevi , Yavas Gokhan , Ge Weigong , Zou Wen , Tong Weida , Hong Huixiao
Published: November 2019

Persistent organic pollutants (POPs) present in foods have been a major concern for food safety due to their persistence and toxic effects. To ensure food safety and protect human health from POPs, it is critical to achieve a better understanding of POP pathways into food and develop strategies to reduce human exposure. POPs could present in food in the raw stages, transferred from the environment or artificially introduced during food preparation steps. Exposure to these pollutants may cause various health problems such as endocrine disruption, cardiovascular diseases, cancers, diabetes, birth defects, and dysfunctional immune and reproductive systems. This review describes potential sources of POP food contamination, analytical approaches to measure POP levels in food and efforts to control food contamination with POPs.
Assessing the Impact of School-Based Greenness on Mental Health Among Adolescent Students in Ontario, Canada
Authors: Srugo Sebastian , de Groh Margaret , Jiang Ying , Morrison Howard , Hamilton Hayley , Villeneuve Paul
Published: November 2019

Neighbourhood greenness has been frequently associated with improved mental health in adulthood, yet its impact among youth is less clear. Additionally, though youth spend large portions of time at school, no study has investigated associations between school-based measures of greenness and students’ mental health in Canada. We addressed this gap by linking participant responses from the 2016–2017 Ontario Student Drug Use and Health Survey to school-based features of the built environment. Our analyses included 6313 students, ages 11–20. Measures of greenness were the mean and max of the annual mean Normalized Difference Vegetation Index within 500 m and 1000 m from the centroid of the school postal code. Measures of mental health included: serious psychological distress (Kessler 6-item Psychological Distress Scale), self-rated mental health (using a five-point Likert scale), suicide ideation, and suicide attempt. In our study population, the prevalence of serious psychological distress and low self-rated mental health was 16.7% and 20.3%, respectively. Suicide ideation was reported by 13.5% of participants, while 3.7% reported a suicide attempt. Quantity of greenness was similar between schools in the lower and upper quartiles. In logistic regressions, we found no association between objective school-based greenness and mental health, as assessed by multiple measures, both before and after adjustment. Null findings held true after stratification by season, as well. Whether other characteristics of school greenness (such as type, quality, or access and use) are more impactful to students’ mental health should be a focus of future analyses.
The Effects of Need Satisfaction and Dissatisfaction on Flourishing among Young Chinese Gamers: The Mediating Role of Internet Gaming Disorder
Authors: Hui Bryant Pui Hung , Wu Anise M. S. , Siu Nicolson Y. F. , Chung Ming-Lun , Pun Ngai
Published: November 2019

Given the increasing popularity of online game playing, the negative impacts of game addiction on both adolescents and adults attracted our attention. Previous studies based on the self-determination theory have examined the effects of the three basic psychological needs of autonomy, competence, and relatedness on problematic video game playing among Chinese young adults. Yet, as more evidence emerged pointing to the possible relation between need dissatisfaction and higher vulnerability for ill-being and psychopathology, the present study aimed to incorporate the impacts of both satisfaction and dissatisfaction for autonomy, competence, and relatedness in explaining Internet gaming disorder (IGD), a condition that may in turn impede eudaimonic well-being as indicated by flourishing. In a self-administered online survey with a valid sample of 1200 Chinese young adults aged 18–24 years (mean age = 19.48 years), the prevalence of probable IGD (for those who reported five or more symptoms in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) symptom list for IGD) was 7.5%. Our results showed that relatedness dissatisfaction positively predicted IGD symptoms after controlling for other need satisfaction and dissatisfaction. Also, flourishing was found to be negatively predicted by IGD. Finally, IGD was found to mediate the effect of relatedness dissatisfaction on flourishing. Our findings suggested a risk factor of relatedness dissatisfaction in predicting IGD, thereby significantly predicting flourishing.
Prohibited Grazing Policy Satisfaction and Life Satisfaction in Rural Northwest China—A Case Study in Yanchi County, Ningxia Hui Autonomous Region
Authors: Wang Weiwei , Zhou Lihua , Yang Guojing , Sun Yan , Chen Yong
Published: November 2019

In order to restore degraded grasslands, the Chinese central government initiated the Prohibited Grazing Policy (PGP) in areas of severe grassland degradation and ecologically fragile regions which is an important payment for ecosystem services (PES) program. Since the initiation of this policy in the early 2000s, the PGP has significantly influenced participants’ lives. Therefore, in order for the policy to be successful, it is necessary to understand what determines participants’ satisfaction in the policy. This paper presents an analysis of survey data from Yanchi County using ordered probit regression models to explore the factors influencing PGP satisfaction and life satisfaction. The empirical results suggest that farmers’ policy perception, environmental perception, and livelihood strategies of raising sheep had significant effects on PGP satisfaction. Additionally, PGP satisfaction, marital status, environmental satisfaction, self-reported influence of the PGP on income, self-reported income level, and self-reported income and expenditure had significantly positive effects on overall life satisfaction. These results are important for promoting better implementation of such programs as well as enhancing social stability and sustainable development in these regions.
Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels
Authors: Zhang Xiaopei , Wang Wei , Zhu Weidong , Dong Jie , Cheng Yingying , Yin Zujun , Shen Fafu
Published: November 2019

Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals. In this review, we summarize the functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels.
Establishing Computational Approaches Towards Identifying Malarial Allosteric Modulators: A Case Study of Plasmodium falciparum Hsp70s
Authors: Amusengeri Arnold , Astl Lindy , Lobb Kevin , Verkhivker Gennady M. , Tastan Bishop Özlem
Published: November 2019

Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malaria cases. To prevent catastrophic results, we need to find non-conventional approaches. Allosteric drug targeting sites and modulators might be a new hope for malarial treatments. Heat shock proteins (HSPs) are potential malarial drug targets and have complex allosteric control mechanisms. Yet, studies on designing allosteric modulators against them are limited. Here, we identified allosteric modulators (SANC190 and SANC651) against P. falciparum Hsp70-1 and Hsp70-x, affecting the conformational dynamics of the proteins, delicately balanced by the endogenous ligands. Previously, we established a pipeline to identify allosteric sites and modulators. This study also further investigated alternative approaches to speed up the process by comparing all atom molecular dynamics simulations and dynamic residue network analysis with the coarse-grained (CG) versions of the calculations. Betweenness centrality (BC) profiles for PfHsp70-1 and PfHsp70-x derived from CG simulations not only revealed similar trends but also pointed to the same functional regions and specific residues corresponding to BC profile peaks.
Tissue-Wide Gene Expression Analysis of Sodium/Phosphate Co-Transporters in Pigs
Authors: Wubuli Aisanjiang , Reyer Henry , Muráni Eduard , Ponsuksili Siriluck , Wolf Petra , Oster Michael , Wimmers Klaus
Published: November 2019

Sodium/phosphate co-transporters are considered to be important mediators of phosphorus (P) homeostasis. The expression of specific sodium/phosphate co-transporters is routinely used as an immediate response to dietary interventions in different species. However, a general understanding of their tissue-specificity is required to elucidate their particular contribution to P homeostasis. In this study, the tissue-wide gene expression status of all currently annotated sodium/phosphate co-transporters were investigated in two pig trials focusing on a standard commercial diet (trial 1) or divergent P-containing diets (trial 2). A wide range of tissues including the gastrointestinal tract (stomach, duodenum, jejunum, ileum, caecum, and colon), kidney, liver, bone, muscle, lung, and aorta were analyzed. Both trials showed consistent patterns in the overall tissue-specific expression of P transporters. While SLC34A2 was considered as the most important intestinal P transporter in other species including humans, SLC34A3 appeared to be the most prominent intestinal P transporter in pigs. In addition, the P transporters of the SLC17 family showed basal expression in the pig intestine and might have a contribution to P homeostasis. The expression patterns observed in the distal colon provide evidence that the large intestine may also be relevant for intestinal P absorption. A low dietary P supply induced higher expressions of SLC20A1, SLC20A2, SLC34A1, and SLC34A3 in the kidney cortex. The results suggest that the expression of genes encoding transcellular P transporters is tissue-specific and responsive to dietary P supply, while underlying regulatory mechanisms require further analyses.
Interspecies Outer Membrane Vesicles (OMVs) Modulate the Sensitivity of Pathogenic Bacteria and Pathogenic Yeasts to Cationic Peptides and Serum Complement
Authors: Roszkowiak Justyna , Jajor Paweł , Guła Grzegorz , Gubernator Jerzy , Żak Andrzej , Drulis-Kawa Zuzanna , Augustyniak Daria
Published: November 2019

The virulence of bacterial outer membrane vesicles (OMVs) contributes to innate microbial defense. Limited data report their role in interspecies reactions. There are no data about the relevance of OMVs in bacterial-yeast communication. We hypothesized that model Moraxella catarrhalis OMVs may orchestrate the susceptibility of pathogenic bacteria and yeasts to cationic peptides (polymyxin B) and serum complement. Using growth kinetic curve and time-kill assay we found that OMVs protect Candida albicans against polymyxin B-dependent fungicidal action in combination with fluconazole. We showed that OMVs preserve the virulent filamentous phenotype of yeasts in the presence of both antifungal drugs. We demonstrated that bacteria including Haemophilus influenza, Acinetobacter baumannii, and Pseudomonas aeruginosa coincubated with OMVs are protected against membrane targeting agents. The high susceptibility of OMV-associated bacteria to polymyxin B excluded the direct way of protection, suggesting rather the fusion mechanisms. High-performance liquid chromatography-ultraviolet spectroscopy (HPLC-UV) and zeta-potential measurement revealed a high sequestration capacity (up to 95%) of OMVs against model cationic peptide accompanied by an increase in surface electrical charge. We presented the first experimental evidence that bacterial OMVs by sequestering of cationic peptides may protect pathogenic yeast against combined action of antifungal drugs. Our findings identify OMVs as important inter-kingdom players.
Combination Radioimmunotherapy Strategies for Solid Tumors
Authors: Zaheer Javeria , Kim Hyeongi , Lee Yong-Jin , Kim Jin Su , Lim Sang Moo
Published: November 2019

Combination radioimmunotherapy is an emerging approach for the treatment of solid tumors where radio immunotherapy alone has proven to be reasonably ineffective. Radioimmunotherapy (RIT) using monoclonal antibodies (mAbs) labeled with radionuclides is an attractive approach for cancer treatment because tumor-associated mAbs with cytotoxic radionuclides can selectively bind to tumor antigens. However, due to various limitations, mAbs cannot reach solid tumors, consequently reducing RIT efficacy. Combination RIT is a pragmatic approach through which the addition of drugs or other agents not only help mAbs to reach the targeted site but also improves its efficacy. Thus, the combination of drugs or moieties with RIT can be applied to overcome the barriers that RIT faces for solid tumors. This review covers the RIT approach, along with the mechanism of action of mAb used in RIT, limitations of solid tumors, and strategies that can be used in combination RIT to enhance the treatment regimen for solid tumors.
Food Allergies and Ageing
Authors: De Martinis Massimo , Sirufo Maria Maddalena , Viscido Angelo , Ginaldi Lia
Published: November 2019

All over the world, there is an increase in the overall survival of the population and the number of elderly people. The incidence of allergic reactions is also rising worldwide. Until recently, allergies, and in particular food allergies (FAs), was regarded as a pediatric problem, since some of them start in early childhood and may spontaneously disappear in adulthood. It is being discovered that, on the contrary, these problems are increasingly affecting even the elderly. Along with other diseases that are considered characteristics of advanced age, such as cardiovascular, dysmetabolic, autoimmune, neurodegenerative, and oncological diseases, even FAs are increasingly frequent in the elderly. An FA is a pleiomorphic and multifactorial disease, characterized by an abnormal immune response and an impaired gut barrier function. The elderly exhibit distinct FA phenotypes, and diagnosis is difficult due to frequent co-morbidities and uncertainty in the interpretation of in vitro and in vivo tests. Several factors render the elderly susceptible to FAs, including the physiological changes of aging, a decline in gut barrier function, the skewing of adaptive immunity to a Th2 response, dysregulation of innate immune cells, and age-related changes of gut microbiota. Aging is accompanied by a progressive remodeling of immune system functions, leading to an increased pro-inflammatory status where type 1 cytokines are quantitatively dominant. However, serum Immunoglobulin E (IgE) levels and T helper type 2 (Th2 cytokine production have also been found to be increased in the elderly, suggesting that the type 2 cytokine pattern is not necessarily defective in older age. Dysfunctional dendritic cells in the gut, defects in secretory IgA, and decreased T regulatory function in the elderly also play important roles in FA development. We address herein the main immunologic aspects of aging according to the presence of FAs.
Designing Microparticle-Impregnated Polyelectrolyte Composite: The Combination of ATRP, Fast Azidation, and Click Reaction Using a Single-Catalyst, Single-Pot Strategy
Authors: De Ranjit , Jung Minhyuk , Lee Hohjai
Published: November 2019

Polystyrene microparticles were covalently impregnated into the networks of functional polyelectrolyte chains designed via a tandem run of three reactions: (i) synthesis of water-soluble polyelectrolyte, (ii) fast azidation and (iii) a ‘click’ reaction, using the single-catalyst, single-pot strategy at room temperature in mild aqueous media. The model polyelectrolyte sodium polystyrenesulfonate (NaPSS) was synthesized via the well-controlled atom transfer radical polymerization (ATRP) whose halogen living-end was transformed to azide and subsequently coupled with an alkyne carboxylic acid through a ‘click’ reaction using the same ATRP catalyst, throughout. Halogen to azide transformation was fast and followed the radical pathway, which was explained through a plausible mechanism. Finally, the success of microparticle impregnation into the NaPSS network was evaluated through Kaiser assay and imaging. This versatile synthetic procedure, having a reduced number of discrete reaction steps and eliminated intermediate work-ups, has established a fast and simple pathway to design functional polymers required to fabricate stable polymer-particle composites where the particles are impregnated covalently and controllably.
Computational Nanoscopy of Tight Junctions at the Blood–Brain Barrier Interface
Authors: Rajagopal Nandhini , Irudayanathan Flaviyan Jerome , Nangia Shikha
Published: November 2019

The selectivity of the blood–brain barrier (BBB) is primarily maintained by tight junctions (TJs), which act as gatekeepers of the paracellular space by blocking blood-borne toxins, drugs, and pathogens from entering the brain. The BBB presents a significant challenge in designing neurotherapeutics, so a comprehensive understanding of the TJ architecture can aid in the design of novel therapeutics. Unraveling the intricacies of TJs with conventional experimental techniques alone is challenging, but recently developed computational tools can provide a valuable molecular-level understanding of TJ architecture. We employed the computational methods toolkit to investigate claudin-5, a highly expressed TJ protein at the BBB interface. Our approach started with the prediction of claudin-5 structure, evaluation of stable dimer conformations and nanoscale assemblies, followed by the impact of lipid environments, and posttranslational modifications on these claudin-5 assemblies. These led to the study of TJ pores and barriers and finally understanding of ion and small molecule transport through the TJs. Some of these in silico, molecular-level findings, will need to be corroborated by future experiments. The resulting understanding can be advantageous towards the eventual goal of drug delivery across the BBB. This review provides key insights gleaned from a series of state-of-the-art nanoscale simulations (or computational nanoscopy studies) performed on the TJ architecture.
Suppression of Human Platelet Activation via Integrin αIIbβ3 Outside-In Independent Signal and Reduction of the Mortality in Pulmonary Thrombosis by Auraptene
Authors: Hsia Chih-Wei , Tsai Cheng-Lin , Sheu Joen-Rong , Lu Wan-Jung , Hsia Chih-Hsuan , Velusamy Marappan , Jayakumar Thanasekaran , Li Jiun-Yi
Published: November 2019

Auraptene is the most abundant coumarin derivative from plants. The pharmacological value of this compound has been well demonstrated, especially in the prevention of cancer and neurodegenerative diseases. Platelet activation is a major factor contributing to arterial thrombosis. Thus, this study evaluated the influence of auraptene in platelet aggregation and thrombotic formation. Auraptene inhibited platelet aggregation in human platelets stimulated with collagen only. However, auraptene was not effective in inhibiting platelet aggregation stimulated with thrombin, arachidonic acid, and U46619. Auraptene also repressed ATP release, [Ca2+]i mobilization, and P-selectin expression. Moreover, it markedly blocked PAC-1 binding to integrin αIIbβ3. However, it had no influence on properties related to integrin αIIbβ3-mediated outside-in signaling, such as the adhesion number, spreading area of platelets, and fibrin clot retraction. Auraptene inhibited the phosphorylation of Lyn-Fyn-Syk, phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), Akt, and mitogen-activated protein kinases (MAPKs; extracellular-signal-regulated kinase (ERK1/2), and c-Jun N-terminal kinase (JNK1/2), but not p38 MAPK). Neither SQ22536, an adenylate cyclase inhibitor, nor ODQ, a guanylate cyclase inhibitor, reversed the auraptene-mediated inhibition of platelet aggregation. Auraptene reduced mortality caused by adenosine diphosphate (ADP)-induced pulmonary thromboembolism. In conclusion, this study provides definite evidence that auraptene signifies a potential therapeutic agent for preventing thromboembolic disorders.
Enhanced Therapeutic Potential of the Secretome Released from Adipose-Derived Stem Cells by PGC-1α-Driven Upregulation of Mitochondrial Proliferation
Authors: Lee Jaeim , Kim Ok-Hee , Lee Sang Chul , Kim Kee-Hwan , Shin Jin Sun , Hong Ha-Eun , Choi Ho Joong , Kim Say-June
Published: November 2019

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.
Novel Crizotinib–GnRH Conjugates Revealed the Significance of Lysosomal Trapping in GnRH-Based Drug Delivery Systems
Authors: Murányi József , Varga Attila , Gyulavári Pál , Pénzes Kinga , Németh Csilla E. , Csala Miklós , Pethő Lilla , Csámpai Antal , Halmos Gábor , Peták István , Vályi-Nagy István
Published: November 2019

Several promising anti-cancer drug–GnRH (gonadotropin-releasing hormone) conjugates have been developed in the last two decades, although none of them have been approved for clinical use yet. Crizotinib is an effective multi-target kinase inhibitor, approved against anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1 (ROS-1)-positive non-small cell lung carcinoma (NSCLC); however, its application is accompanied by serious side effects. In order to deliver crizotinib selectively into the tumor cells, we synthesized novel crizotinib analogues and conjugated them to a [d-Lys6]–GnRH-I targeting peptide. Our most prominent crizotinib–GnRH conjugates, the amide-bond-containing [d-Lys6(crizotinib*)]–GnRH-I and the ester-bond-containing [d-Lys6(MJ55*)]–GnRH-I, were able to bind to GnRH-receptor (GnRHR) and exert a potent c-Met kinase inhibitory effect. The efficacy of compounds was tested on the MET-amplified and GnRHR-expressing EBC-1 NSCLC cells. In vitro pharmacological profiling led to the conclusion that that crizotinib–GnRH conjugates are transported directly into lysosomes, where the membrane permeability of crizotinib is diminished. As a consequence of GnRHR-mediated endocytosis, GnRH-conjugated crizotinib bypasses its molecular targets—the ATP-binding site of RTKs— and is sequestered in the lysosomes. These results explained the lower efficacy of crizotinib–GnRH conjugates in EBC-1 cells, and led to the conclusion that drug escape from the lysosomes is a major challenge in the development of clinically relevant anti-cancer drug–GnRH conjugates.