bluuebunny/crossref_metadata_2025 huggingface dataset:
An Overview of Modelling Techniques and Control Strategies for Modular Multilevel Matrix Converters
Authors: Diaz Matias , Cardenas Roberto , Ibaceta Efrain , Mora Andrés , Urrutia Matias , Espinoza Mauricio , Rojas Felix , Wheeler Patrick
Published: September 2020

The Modular Multilevel Matrix Converter is a relatively new power converter topology appropriate for high-power Alternating Current (AC) to AC purposes. Several publications in the literature have highlighted the converter capabilities such as modularity, control flexibility, the possibility to include redundancy, and power quality. Nevertheless, the topology and control of this converter are relatively complex to design and implement, considering that the converter has a large number of cells and floating capacitors. Therefore multilayer nested control systems are required to maintain the capacitor voltage of each cell regulated within an acceptable range. There are no other review papers where the modelling, control systems and applications of the Modular Multilevel Matrix Converter are discussed. Hence, this paper aims to facilitate further research by presenting the technology related to the Modular Multilevel Matrix Converter, focusing on a comprehensive revision of the modelling and control strategies.
On the Investigation of Microstructured Charcoal as an ANFO Blasting Enhancer
Authors: Atlagic Suzana Gotovac , Biessikirski Andrzej , Kuterasiński Łukasz , Dworzak Michał , Twardosz Michał , Sorogas Niki , Arvanitidis John
Published: September 2020

In this study, we examined the influence of microstructured charcoal (MC) when added to ammonium nitrate fuel oil (ANFO) samples. We performed a study that investigated ANFOs structure, crystallinity, and morphology by utilizing infrared spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscopy (SEM), respectively. MC characteristics were probed by Raman spectroscopy and SEM analysis. SEM analysis indicated how fuel oil (FO) covered ammonium nitrate prill. Moreover, the surface of the MC was covered by specific microfibers and microtubes. The disordered graphitic structure of the MC was also confirmed by Raman spectroscopy. Simulation of blasting properties revealed that the addition of MC should decrease blasting parameters like heat explosion, detonation pressure, and detonation temperature. However, the obtained differences are negligible in comparison with the regular ANFO. All analyses indicated that MC was a good candidate as an additive to ANFO.
Validation and Evaluation of an Estimation Method for Deep Thermal Structures Using an Activity Index in Major Geothermal Fields in Northeastern Japan
Authors: Suzuki Yota , Muraoka Hirofumi , Asanuma Hiroshi
Published: September 2020

A considerable number of rock bodies with varying percentages of supercritical fluid exist around the brittle–ductile transition (BDT) zone at a depth of several kilometers from the surface of the Earth, in northeastern Japan. As the BDT zone in the granitic basement of the continental crust is estimated to occur at about 380 °C, the identification of the depth corresponding to 380 °C is important to utilize the thermal energy inside the “supercritical geothermal systems”. In this study, we focused on an estimation method to determine the depth of the isothermal layer corresponding to 380 °C, using the activity index (AI) obtained from the maximum-temperature data of the geothermal wells and hot springs. The thermal profiles of deep and hot exploration boreholes and the hypocentral distribution of natural earthquakes were used to evaluate the characteristics and accuracy of the deep thermal structure, using the activity index. The estimated depth corresponding to 380 °C tended to be higher than the actual depth, with a maximum possible estimation error of approximately 9.7 km. Distribution maps showing the depth of the isothermal layer corresponding to 380 °C were created for six major geothermal fields in northeastern Japan, using the results from this study.
Cationic Dye Adsorption on Hydrochars of Winery and Citrus Juice Industries Residues: Performance, Mechanism, and Thermodynamics
Authors: Saha Nepu , Volpe Maurizio , Fiori Luca , Volpe Roberto , Messineo Antonio , Reza M. Toufiq
Published: September 2020

With the increasing needs of clean water supplies, the use of biomass wastes and residues for environmental remediation is essential for environmental sustainability. In this study, the residues from winery and citrus juice industries, namely grape skin and orange peel, respectively, were first converted to hydrochars by hydrothermal carbonization (HTC) and then a cationic dye (methylene blue) adsorption was studied on hydrochars. Hydrochars from both feedstocks were produced at three different temperatures (180, 220, and 250 °C) and a fixed residence time (1 h) to evaluate the hydrochar’s performance on the dye adsorption. The hydrochars were characterized in terms of their pH, pH at point of zero charge (pHPZC), surface functionalities, and surface area. A batch adsorption study of the dye was carried out with variable adsorbate concentration, pH, and temperature. Two adsorption isotherms namely Langmuir and Freundlich models were fitted at 4, 20, and 36 °C. The thermodynamic properties of adsorption (Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS)) were evaluated from the isotherms fittings. Results showed that the dye adsorption on both hydrochars was significant and followed Langmuir isotherm. The maximum adsorption capacity on citrus waste hydrochar was higher than the winery waste hydrochar at any corresponding HTC temperature. Although hydrochars showed the lowest surface area (46.16 ± 0.11 and 34.08 ± 1.23 m2/g for citrus and winery wastes, respectively) at 180 °C, their adsorption was the highest, owing to their maximum density of total oxygen functional groups (23.24 ± 0.22 and 32.69 ± 1.39 µmol/m2 for citrus and winery wastes, respectively), which decreased with the increase in HTC temperature. This research shows a sustainable route for the production of highly effective adsorbent materials at lower HTC temperatures from citrus and winery wastes.
Validating CFD Predictions of Flow over an Escarpment Using Ground-Based and Airborne Measurement Devices
Authors: El Bahlouli Asmae , Leukauf Daniel , Platis Andreas , zum Berge Kjell , Bange Jens , Knaus Hermann
Published: September 2020

Micrometeorological observations from a tower, an eddy-covariance (EC) station and an unmanned aircraft system (UAS) at the WINSENT test-site are used to validate a computational fluid dynamics (CFD) model, driven by a mesoscale model. The observation site is characterised by a forested escarpment in a complex terrain. A two-day measurement campaign with a flow almost perpendicular to the escarpment is analysed. The first day is dominated by high wind speeds, while, on the second one, calm wind conditions are present. Despite some minor differences, the flow structure, analysed in terms of horizontal wind speeds, wind direction and inclination angles shows similarities for both days. A real-time strategy is used for the CFD validation with the UAS measurement, where the model follows spatially and temporally the aircraft. This strategy has proved to be successful. Stability indices such as the potential temperature and the bulk Richardson number are calculated to diagnose atmospheric boundary layer (ABL) characteristics up to the highest flight level. The calculated bulk Richardson values indicate a dynamically unstable region behind the escarpment and near the ground for both days. At higher altitudes, the ABL is returning to a near neutral state. The same characteristics are found in the model but only for the first day. The second day, where shear instabilities are more dominant, is not well simulated. UAS proves its great value for sensing the flow over complex terrains at high altitudes and we demonstrate the usefulness of UAS for validating and improving models.
System Design and Modeling of a High Temperature PEM Fuel Cell Operated with Ammonia as a Fuel
Authors: Cinti Giovanni , Liso Vincenzo , Sahlin Simon Lennart , Araya Samuel Simon
Published: September 2020

Ammonia is a hydrogen-rich compound that can play an important role in the storage of green hydrogen and the deployment of fuel cell technologies. Nowadays used as a fertilizer, NH3 has the right peculiarities to be a successful sustainable fuel for the future of the energy sector. This study presents, for the first time in literature, an integration study of ammonia as a hydrogen carrier and a high temperature polymer electrolyte membrane fuel cell (HT-PEMFC) as an energy conversion device. A system design is presented, that integrates a reactor for the decomposition of ammonia with an HT-PEMFC, where hydrogen produced from NH3 is electrochemically converted into electricity and heat. The overall system based on the two technologies is designed integrating all balance of plant components. A zero-dimensional model was implemented to evaluate system efficiency and study the effects of parametric variations. Thermal equilibrium of the decomposition reactor was studied, and two different strategies were implemented in the model to guarantee thermal energy balance inside the system. The results show that the designed system can operate with an efficiency of 40.1% based on ammonia lower heating value (LHV) at the fuel cell operating point of 0.35 A/cm2 and 0.60 V.
Intensification of Short Chain Fatty Acid Production during the Alkaline Pretreatment of Fine-Sieving Fractions
Authors: Duan Yanqing , Zhou Aijuan , Yue Xiuping , Zhang Zhichun , Gao Yanjuan , Luo Yanhong
Published: September 2020

Maximizing the internal carbon sources in raw wastewater was found to be an alternative option to alleviate the financial burden in external carbon sources (ECS) addition to the biological nutrient removal (BNR) process. Based on previous studies on particulate recovery via fine-sieving technologies, alkali pretreatment was used to improve the short-chain fatty acid (SCFA) production from the fine-sieving fractions (FSF). Hydrolysis performance and methane production were monitored to evaluate the reasons for the SCFA boost. Besides, the microbial community structure was evaluated by high-throughput sequencing. Furthermore, mass balance and financial benefits were preliminarily estimated. The results showed that alkali pretreatment effectively promoted the generation of SCFAs with 234 mg/g volatile suspended solids (VSS), almost double that of the control test. This was partially attributed to the efficient hydrolysis, with soluble polysaccharides and protein increased by 2.1 and 1.2 times compared to that of the control, respectively. Inhibition of methanogens was also devoted to the accumulation of SCFAs, with no methane production until 150 h at high pH value. Finally, a preliminary evaluation revealed that 44.51 kg/d SCFAs could be supplied as the electron donor for denitrification, significantly reducing the cost in ECS addition for most wastewater treatment plants (WWTPs) with carbon insufficiency.
HV Transformer Protection and Stabilization under Geomagnetically Induced Currents
Authors: Bejmert Daniel , Boehme Klaus , Kereit Matthias , Rebizant Waldemar
Published: September 2020

This paper presents the results of research related to the issues arising from DC excitation of power transformers due to geomagnetically induced currents (GIC). First, the GIC phenomena and their influence on power system operation are discussed. Then, a recorded case of tripping of the transformer differential protection due to geomagnetic disturbances (GD), as well as simulation signals from a developed model of a transformer subjected to a GD are analyzed. Next, two algorithms for GIC detection utilizing the rate of change of transformer differential currents and the DC component in the neutral current are proposed, thoroughly tested, and recommended.
Experimental Study on the Solids Residence Time Distribution in Multiple Square-Based Spouted Beds
Authors: Marchelli Filippo , Curti Massimo , Tognin Mattia , Rovero Giorgio , Moliner Cristina , Arato Elisabetta , Bosio Barbara
Published: September 2020

The present work aims at investigating the residence time distribution (RTD) of a multiple spouted bed reactor, which will be applied for the pyrolysis and gasification of residual biomass. The unit is composed of square-based spouted beds, placed in series and at descending heights, and communicating with each other through an opening in the lateral wall. The gas is fed evenly in parallel. The experimental analysis is based on tracer experiments in cold-flow units, assessing the influence of the number of units and the bed height. The tests proved the good mixing properties of the spouted beds, which create a stable fluidization regime and do not feature dead zones. Each spouted bed can generally be well assimilated to an ideal continuous stirred tank reactor (CSTR). The RTD of the device seems adequate for the application, and also seems to be well tuneable through the selection of the bed height and number of units. Given the good similarity with ideal reactor networks, these represent a valid tool to estimate the final behavior in terms of RTD.
Systemic Evaluation of the Effects of Regional Self-Supply Targets on the German Electricity System Using Consistent Scenarios and System Optimization
Authors: Senkpiel Charlotte , Hauser Wolfgang
Published: September 2020

This paper analyses the effects of regional renewable electricity self-sufficiency targets on the power system in Germany. For this purpose, an interdisciplinary approach from social sciences and energy system modelling was chosen, which allows considering qualitative factors such as public acceptance or political stability. Following the concept of context scenarios, consistent raw scenarios are generated by a cross-impact balance analysis (CIB), and the scenarios are quantified by the unit commitment and expansion cost minimisation model ENTIGRIS considering power plants, storages, and the electricity grid. This approach enables an understanding of the system framework conditions and their relationships and allows the combination of qualitative and quantitative scenario descriptors. The most important factors for setting regional self-sufficiency targets were identified through interviews. The main system effects identified are: The regional distribution of generation capacities is strongly influenced by a more demand-oriented installation of generation capacities. This leads to less grid reinforcement, but higher rates of curtailment. In all scenarios, higher utilization of the PV roof potential instead of ground mounted could be observed. The total system costs are increasing only slightly with regional self-supply targets. In general, it was found that the influence of regional self-sufficiency targets is less pronounced in scenarios that already achieve high national RES shares than in scenarios that achieve lower shares, since technology, storage and grid expansion measures are necessary anyway to achieve high RES shares. Overall, the effects here are rather small and the regional objective is not associated with major disadvantages for the system. In a future characterised by stagnation, the system can benefit from regional targeting, as higher renewable shares and lower costs can result. The main conclusion therefore is that regional target setting seem to be beneficial for the overall power system, in terms of system cost, national RE share, acceptance and CO2-emissions.
Restoration of Missing Pressures in a Gas Well Using Recurrent Neural Networks with Long Short-Term Memory Cells
Authors: Ki Seil , Jang Ilsik , Cha Booho , Seo Jeonggyu , Kwon Oukwang
Published: September 2020

This study proposes a data-driven method based on recurrent neural networks (RNNs) with long short-term memory (LSTM) cells for restoring missing pressure data from a gas production well. Pressure data recorded by gauges installed at the bottom hole and wellhead of a production well often contain abnormal or missing values as a result of gauge malfunctions, noise, outliers, and operational instability. RNNs employing LSTM cells to prevent long-term memory loss have been widely used to predict time series data. In this study, an RNN with the LSTM method was used to restore abnormal or missing wellhead and bottom-hole pressures in three intervals within a production sequence of more than eight years in duration. The pressure restoration was performed using various input features for RNNs with LSTM models based on the characteristics of the available data. It was carried out through three sequential processes and the results were acceptable with a mean absolute percentage error no more than 5.18%. The reliability of the proposed method was verified through a comparison with the results of a physical model.
Experimental and Numerical Study on Energy Piles with Phase Change Materials
Authors: Mousa M. M. , Bayomy A. M. , Saghir M. Z.
Published: September 2020

Phase change materials (PCM) utilization in energy storage systems represents a point of interest and attraction for the researchers to reduce greenhouse gas emissions. PCM have been used widely on the interior or exterior walls of the building application to optimize the energy consumption during heating and cooling periods. Meanwhile, ground source heat pump (GSHP) gained its popularity because of the high coefficient of performance (COP) and low running cost of the system. However, GSHP system requires a stand-by heat pump during peak loads. This study will present a new concept of energy piles that used PCM in the form of enclosed tube containers. A lab-scaled foundation pile was developed to examine the performance of the present energy pile, where three layers of insulation replaced the underground soil to focus on the effect of PCM. The investigation was conducted experimentally and numerically on two identical piles with and without PCM. Moreover, a flow rate parametric study was conducted to study the effect of the working fluid flow rate on the amount of energy stored and released at each model. Finally, a comprehensive Computational fluid dynamic (CFD) model was developed and compared with the experimental results. There was a good agreement between the experimental measurements and the numerical predictions. The results revealed that the presence of PCM inside the piles increased not only the charging and discharging capacity but also the storage efficiency of the piles. It was found that PCM enhances the thermal response of the concrete during cooling and heating processes. Although increasing the flow rate increased charging and discharging capacity, the percentage of energy stored/released was insignificant compared to the flow rate increasing percentage.
Influence of Polymer Reagents in the Drilling Fluids on the Efficiency of Deviated and Horizontal Wells Drilling
Authors: Liu Tianle , Leusheva Ekaterina , Morenov Valentin , Li Lixia , Jiang Guosheng , Fang Changliang , Zhang Ling , Zheng Shaojun , Yu Yinfei
Published: September 2020

Improving the efficiency of well drilling process in a reservoir is directly related to subsequent well flow rates. Drilling of deviated and horizontal wells is often accompanied by an increase in pressure losses due to flow resistance caused by small size of the annular space. An important role in such conditions is played by the quality of borehole cleaning and transport capacity of drilling fluid, which is directly related to the rheological parameters of the drilling fluid. The main viscosifiers in modern drilling fluids are polymer reagents. They can be of various origin and structure, which determines their features. This work presents investigations that assess the effect of various polymers on the rheological parameters of drilling fluids. Obtained data are evaluated taking into account the main rheological models of fluid flow. However, process of fluid motion during drilling cannot be described by only one flow model. Paper shows experimentally obtained data of such indicators as plastic viscosity, dynamic shear stress, non-linearity index and consistency coefficient. Study has shown that high molecular weight polymer reagents (e.g., xanthan gum) can give drilling fluid more pronounced pseudoplastic properties, and combining them with a linear high molecular weight polymer (e.g., polyacrylamide) can reduce the value of the dynamic shear stress. Results of the work show the necessity of using combinations of different types of polymer reagents, which can lead to a synergetic effect. In addition to assessing the effect of various polymer reagents, the paper presents study on the development of a drilling fluid composition for specific conditions of an oil field.
Solar Cycles in Salvage Logging: National Data from the Czech Republic Confirm Significant Correlation
Authors: Šimůnek Václav , Vacek Zdeněk , Vacek Stanislav
Published: September 2020

Forest ecosystems in Europe undergo cyclic fluctuations with alternating periods of forest prosperity and disturbances. Forest disturbances are caused by large-scale calamities (climate-induced and unforeseen events) resulting in an increased volume of salvage logging. In recent decades, climate change (warming, long-term droughts, more frequent storms, bark beetle outbreaks) has contributed to an increased frequency of salvage logging. However, until now, it has not been revealed what triggers national-scale forest calamities. All of the above-mentioned natural disturbances are connected to solar activity, which is the driver of climate change. This research relates the total volume of harvested timber and salvage logging to the climate and cosmic factors in the Czech Republic, Central Europe. Data of total and salvage logging are compared with air temperatures, precipitation, extreme climatic events, sunspot areas, and cosmic ray intensities. The results document a significant effect of average annual temperatures on the total and salvage logging for the entire period of observations since 1961. A significant correlation of salvage logging to the sunspot area and cosmic ray intensity was observed. The link between salvage logging and sunspots and cosmic ray intensity is supported by spectral analysis in which a significant 11-year cycle was observed since 1973. The results also show an increasing significant effect of sunspots and cosmic ray intensity on logging in recent years in connection with synergism of extreme climate events and the subsequent bark beetle outbreaks. Space and cosmic effects are factors that substantially influence forest ecosystems. Therefore, this paper provides new knowledge about, and possible predictions of, the forest response under climate change.
Personality, Healthcare Use and Costs—A Systematic Review
Authors: Hajek André , Kretzler Benedikt , König Hans-Helmut
Published: September 2020

Background: Thus far, there is a lack of a systematic review synthesizing empirical studies that analyze the link between personality factors and healthcare use (HCU) or costs. Consequently, the purpose of our systematic review is to give an overview of empirical findings from observational studies examining the association between personality factors and HCU or costs. Methods: PubMed, PsycINFO, and NHS EED (NHS Economic Evaluation Database) were searched. Observational studies examining the association between personality factors and HCU costs by using validated tools were included. Two reviewers performed study selection and data extraction and evaluated the study quality. Findings were synthesized qualitatively. Results: In total, n = 15 studies (HCU, n = 14; cost studies, n = 1) were included in the final synthesis. A few studies point to an association between conscientiousness and HCU (with mixed evidence). Some more evidence was found for an association between higher agreeableness, higher extraversion, and higher openness to experience and increased HCU. The majority of studies analyzed found a link between higher neuroticism and increased HCU. Conclusion: Personality factors, and particularly neuroticism, are associated with HCU. This knowledge is important to manage healthcare use. However, future research based on longitudinal data and studies investigating the link between personality characteristics and costs are required.
Development and Evaluation of a Water Quality Index for the Iraqi Rivers
Authors: Ewaid Salam , Abed Salwan , Al-Ansari Nadhir , Salih Riyadh
Published: September 2020

Water quality evaluation is fundamental for water resources management. Water quality index (WQI) is an accurate and easily understandable method for assessing water quality for different purposes. In this study, the Iraqi water quality index (Iraq WQI) was constructed to be used to evaluate the Iraqi rivers for drinking. For this purpose, some statistical techniques, experts’ advice, literature reviews, and authors’ experience were used. First, the principal component analysis (PCA) method and the modified Delphi method were used to select the most influential water quality parameters and their relative weights. Second, the quality curves of selected parameters were drawn to calculate the WQI scores basing on the water quality standards. Of twenty-seven parameters, six parameters were chosen to be within the index depending on their effect on water quality in order to reflect the specific characteristics of the Iraqi waters. The Iraq WQI was applied to the Tigris River within Baghdad as a case study and for some sites on other Iraqi rivers, and gave acceptable results. Results revealed that the statistical techniques used in this paper can be applied in all Iraqi rivers considering their specific characteristics. Based on the reliability of the Iraq WQI, there is no longer a need to use Indices designed for water for other countries.
Perceived Stress, Stigma, Traumatic Stress Levels and Coping Responses amongst Residents in Training across Multiple Specialties during COVID-19 Pandemic—A Longitudinal Study
Authors: Chew Qian Hui , Chia Faith Li-Ann , Ng Wee Khoon , Lee Wan Cheong Ivan , Tan Pei Lin Lynnette , Wong Chen Seong , Puah Ser Hon , Shelat Vishalkumar G. , Seah Ee-Jin Darren , Huey Cheong Wei Terence , Phua Eng Joo , Sim Kang
Published: September 2020

This study aimed to explore changes in psychological responses (perceived stress, traumatic stress, stigma, coping) over time in residents, as well as their predictors. The level of perceived stress, traumatic stress, stigma, and coping responses were assessed using the Perceived Stress Scale, Impact of Event-Revised, Healthcare Workers Stigma Scale, and Brief Coping Orientation to Problems Experienced (COPE) Inventory, respectively. We collected responses from 274 residents at baseline and 221 residents at 3 months follow-up (timepoint 2) from the National Healthcare Group (NHG) residency programs in Singapore. All residents reported lower perceived stress and lower perceived stigma compared to baseline. Use of avoidance coping was associated with all three psychological responses (perceived stress, traumatic stress, and stigma) across the two timepoints. Compared to baseline, specific factors associated with perceived stress and traumatic stress at timepoint 2 were living alone, less problem solving, and seeking social support. Residency programs should encourage active coping strategies (e.g., seeking social support, positive thinking, problem solving) among residents, and proactively identify residents who may be at higher risk of psychological sequelae due to circumstances that contribute to isolation.
Molecular Mechanisms of Reconsolidation-Dependent Memory Updating
Authors: Bellfy Lauren , Kwapis Janine L.
Published: September 2020

Memory is not a stable record of experience, but instead is an ongoing process that allows existing memories to be modified with new information through a reconsolidation-dependent updating process. For a previously stable memory to be updated, the memory must first become labile through a process called destabilization. Destabilization is a protein degradation-dependent process that occurs when new information is presented. Following destabilization, a memory becomes stable again through a protein synthesis-dependent process called restabilization. Much work remains to fully characterize the mechanisms that underlie both destabilization and subsequent restabilization, however. In this article, we briefly review the discovery of reconsolidation as a potential mechanism for memory updating. We then discuss the behavioral paradigms that have been used to identify the molecular mechanisms of reconsolidation-dependent memory updating. Finally, we outline what is known about the molecular mechanisms that support the memory updating process. Understanding the molecular mechanisms underlying reconsolidation-dependent memory updating is an important step toward leveraging this process in a therapeutic setting to modify maladaptive memories and to improve memory when it fails.
mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection
Authors: Xu Shuqin , Yang Kunpeng , Li Rose , Zhang Lu
Published: September 2020

Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. At the same time, some suggestions for future mRNA vaccine development about storage methods, safety concerns, and personalized vaccine synthesis can be found in the context.
Consensus-Based Pharmacophore Mapping for New Set of N-(disubstituted-phenyl)-3-hydroxyl-naphthalene-2-carboxamides
Authors: Bak Andrzej , Kos Jiri , Michnova Hana , Gonec Tomas , Pospisilova Sarka , Kozik Violetta , Cizek Alois , Smolinski Adam , Jampilek Josef
Published: September 2020

A series of twenty-two novel N-(disubstituted-phenyl)-3-hydroxynaphthalene- 2-carboxamide derivatives was synthesized and characterized as potential antimicrobial agents. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[2-chloro-5-(trifluoromethyl)phenyl]-3-hydroxy- naphthalene-2-carboxamide showed submicromolar (MICs 0.16–0.68 µM) activity against methicillin-resistant Staphylococcus aureus isolates. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[4-bromo-3-(trifluoromethyl)phenyl]-3-hydroxynaphthalene-2-carboxamide revealed activity against M. tuberculosis (both MICs 10 µM) comparable with that of rifampicin. Synergistic activity was observed for the combinations of ciprofloxacin with N-[4-bromo-3-(trifluoromethyl)phenyl]- and N-(4-bromo-3-fluorophenyl)-3-hydroxynaphthalene-2-carboxamides against MRSA SA 630 isolate. The similarity-related property space assessment for the congeneric series of structurally related carboxamide derivatives was performed using the principal component analysis. Interestingly, different distribution of mono-halogenated carboxamide derivatives with the –CF3 substituent is accompanied by the increased activity profile. A symmetric matrix of Tanimoto coefficients indicated the structural dissimilarities of dichloro- and dimetoxy-substituted isomers from the remaining ones. Moreover, the quantitative sampling of similarity-related activity landscape provided a subtle picture of favorable and disallowed structural modifications that are valid for determining activity cliffs. Finally, the advanced method of neural network quantitative SAR was engaged to illustrate the key 3D steric/electronic/lipophilic features of the ligand-site composition by the systematic probing of the functional group.
Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15+ Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma
Authors: Chen Samantha M. Y. , Li Bian , Nicklawsky Andrew G. , Krinsky Alexandra L. , Brunetti Tonya , Woolaver Rachel A. , Wang Xiaoguang , Chen Zhangguo , Young Christian D. , Gao Dexiang , Wang Xiao-Jing , Wang Jing H.
Published: September 2020

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and loss-of-function mutations of tumor protein p53 (TP53). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME). It also remains unknown whether PIK3CA hyperactivation and TP53 deletion can lead to SCC development spontaneously. Here, we analyzed the Cancer Genome Atlas (TCGA) datasets of HNSCCs and found that patients with both PIK3CA and TP53 alterations exhibited worse survival, significantly lower CD8 tumor infiltrating lymphocytes (TILs) and higher M0 macrophages than other controls. To better model human tumorigenesis, we deleted TP53 and constitutively activated PIK3CA in mouse keratin-15-expressing stem cells, which leads to the spontaneous development of multilineage tumors including SCCs, termed Keratin-15-p53-PIK3CA (KPPA) tumors. KPPA tumors were heavily infiltrated with myeloid-derived suppressor cells (MDSCs), with a drastically increased ratio of polymorphonuclear-MDSC (PMN-MDSC) versus monocytic-MDSC (M-MDSC). CD8 TILs expressed more PD-1 and reduced their polyfunctionality. Overall, we established a genetic model to mimic human HNSCC pathogenesis, manifested with an immunosuppressive TME, which may help further elucidate immune evasion mechanisms and develop more effective immunotherapies for HNSCCs.
The Crosstalk between Microbiome and Immune Response in Gastric Cancer
Authors: Nasr Rihab , Shamseddine Ali , Mukherji Deborah , Nassar Farah , Temraz Sally
Published: September 2020

Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host’s immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk between the gut microbiome and immune response in gastric cancer.
Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment
Authors: De Pasquale Valeria , Pavone Luigi Michele
Published: September 2020

In the last few decades, heparan sulfate (HS) proteoglycans (HSPGs) have been an intriguing subject of study for their complex structural characteristics, their finely regulated biosynthetic machinery, and the wide range of functions they perform in living organisms from development to adulthood. From these studies, key roles of HSPGs in tumor initiation and progression have emerged, so that they are currently being explored as potential biomarkers and therapeutic targets for cancers. The multifaceted nature of HSPG structure/activity translates in their capacity to act either as inhibitors or promoters of tumor growth and invasion depending on the tumor type. Deregulation of HSPGs resulting in malignancy may be due to either their abnormal expression levels or changes in their structure and functions as a result of the altered activity of their biosynthetic or remodeling enzymes. Indeed, in the tumor microenvironment, HSPGs undergo structural alterations, through the shedding of proteoglycan ectodomain from the cell surface or the fragmentation and/or desulfation of HS chains, affecting HSPG function with significant impact on the molecular interactions between cancer cells and their microenvironment, and tumor cell behavior. Here, we overview the structural and functional features of HSPGs and their signaling in the tumor environment which contributes to tumorigenesis and cancer progression.
Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines
Authors: Paukovcekova Silvia , Valik Dalibor , Sterba Jaroslav , Veselska Renata
Published: September 2020

The main objective of this study was to analyze changes in the antiproliferative effect of vitamin D3, in the form of calcitriol and calcidiol, via its combined application with all-trans retinoic acid (ATRA) in osteosarcoma cell lines. The response to treatment with calcitriol and calcidiol alone was specific for each cell line. Nevertheless, we observed an enhanced effect of combined treatment with ATRA and calcitriol in the majority of the cell lines. Although the levels of respective nuclear receptors did not correlate with the sensitivity of cells to these drugs, vitamin D receptor (VDR) upregulation induced by ATRA was found in cell lines that were the most sensitive to the combined treatment. In addition, all these cell lines showed high endogenous levels of retinoic acid receptor α (RARα). Our study confirmed that the combination of calcitriol and ATRA can achieve enhanced antiproliferative effects in human osteosarcoma cell lines in vitro. Moreover, we provide the first evidence that ATRA is able to upregulate VDR expression in human osteosarcoma cells. According to our results, the endogenous levels of RARα and VDR could be used as a predictor of possible synergy between ATRA and calcitriol in osteosarcoma cells.
Real-Time Visualization of Cellulase Activity by Microorganisms on Surface
Authors: Kumari Pallavi , Sayas Tali , Bucki Patricia , Brown-Miyara Sigal , Kleiman Maya
Published: September 2020

A variety of methods to detect cellulase secretion by microorganisms has been developed over the years, none of which enables the real-time visualization of cellulase activity on a surface. This visualization is critical to study the interaction between soil-borne cellulase-secreting microorganisms and the surface of plant roots and specifically, the effect of surface features on this interaction. Here, we modified the known carboxymethyl cellulase (CMC) hydrolysis visualization method to enable the real-time tracking of cellulase activity of microorganisms on a surface. A surface was formed using pure CMC with acridine orange dye incorporated in it. The dye disassociated from the film when hydrolysis occurred, forming a halo surrounding the point of hydrolysis. This enabled real-time visualization, since the common need for post hydrolysis dyeing was negated. Using root-knot nematode (RKN) as a model organism that penetrates plant roots, we showed that it was possible to follow microorganism cellulase secretion on the surface. Furthermore, the addition of natural additives was also shown to be an option and resulted in an increased RKN response. This method will be implemented in the future, investigating different microorganisms on a root surface microstructure replica, which can open a new avenue of research in the field of plant root–microorganism interactions.
Genome-Wide Identification, Characterization and Expression Analysis of TCP Transcription Factors in Petunia
Authors: Zhang Shuting , Zhou Qin , Chen Feng , Wu Lan , Liu Baojun , Li Fei , Zhang Jiaqi , Bao Manzhu , Liu Guofeng
Published: September 2020

The plant-specific TCP transcription factors are well-characterized in both monocots and dicots, which have been implicated in multiple aspects of plant biological processes such as leaf morphogenesis and senescence, lateral branching, flower development and hormone crosstalk. However, no systematic analysis of the petunia TCP gene family has been described. In this work, a total of 66 petunia TCP genes (32 PaTCP genes in P. axillaris and 34 PiTCP genes in P. inflata) were identified. Subsequently, a systematic analysis of 32 PaTCP genes was performed. The phylogenetic analysis combined with structural analysis clearly distinguished the 32 PaTCP proteins into two classes—class Ι and class Ⅱ. Class Ⅱ was further divided into two subclades, namely, the CIN-TCP subclade and the CYC/TB1 subclade. Plenty of cis-acting elements responsible for plant growth and development, phytohormone and/or stress responses were identified in the promoter of PaTCPs. Distinct spatial expression patterns were determined among PaTCP genes, suggesting that these genes may have diverse regulatory roles in plant growth development. Furthermore, differential temporal expression patterns were observed between the large- and small-flowered petunia lines for most PaTCP genes, suggesting that these genes are likely to be related to petal development and/or petal size in petunia. The spatiotemporal expression profiles and promoter analysis of PaTCPs indicated that these genes play important roles in petunia diverse developmental processes that may work via multiple hormone pathways. Moreover, three PaTCP-YFP fusion proteins were detected in nuclei through subcellular localization analysis. This is the first comprehensive analysis of the petunia TCP gene family on a genome-wide scale, which provides the basis for further functional characterization of this gene family in petunia.
Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma
Authors: Chen Chao-Cheng , Chen Yang-Yi , Lo Yi-Hsuan , Lin Ming-Hsien , Chang Chih-Hsien , Chen Chuan-Lin , Wang Hsin-Ell , Wu Chun-Yi
Published: September 2020

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.
STIM1 Deficiency Leads to Specific Down-Regulation of ITPR3 in SH-SY5Y Cells
Authors: Pascual-Caro Carlos , Orantos-Aguilera Yolanda , Sanchez-Lopez Irene , de Juan-Sanz Jaime , Parys Jan B. , Area-Gomez Estela , Pozo-Guisado Eulalia , Martin-Romero Francisco Javier
Published: September 2020

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca2+ channel, STIM1 activates the ICRAC current, whereas the binding with the voltage-operated Ca2+ channel CaV1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer’s disease, a decrease of STIM1 protein levels accounts for the alteration of Ca2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca2+ channel enriched at ER-mitochondria contact sites where it provides Ca2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca2+ concentration ([Ca2+]mit), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca2+]mit mediated by the STIM1-ITPR3 axis.
Proteomic Approach for Searching for Universal, Tissue-Specific, and Line-Specific Markers of Extracellular Vesicles in Lung and Colorectal Adenocarcinoma Cell Lines
Authors: Novikova Svetlana , Shushkova Natalia , Farafonova Tatiana , Tikhonova Olga , Kamyshinsky Roman , Zgoda Victor
Published: September 2020

Tumor-derived extracellular vesicles (EVs), including exosomes, contain proteins that mirror the molecular landscape of producer cells. Being potentially detectible in biological fluids, EVs are of great interest for the screening of cancer biomarkers. To reveal universal, tissue-specific, and line-specific markers, we performed label-free mass spectrometric profiling of EVs originating from the human colon cancer cell lines Caco-2, HT29, and HCT-116, as well as from the lung cancer cell lines NCI-H23 and A549. A total of 651 proteins was identified in the EV samples using at least two peptides. These proteins were highly enriched in exosome markers. We found 11 universal, eight tissue-specific, and 29 line-specific markers, the levels of which were increased in EVs compared to the whole lysates. The EV proteins were involved in the EGFR, Rap1, integrin, and microRNA signaling associated with metastasis and cancer progression. An EV protein-based assay could be developed as a liquid biopsy tool.