bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Same Selected Immunomodulatory Properties of Chorionic Mesenchymal Stem Cells
Authors: Bačenková Darina , Trebuňová Marianna , Zachar Lukáš , Hudák Radovan , Ižaríková Gabriela , Šurínová Katarína , Živčák Jozef
Published: December 2020

Mesenchymal stem cells (MSCs) represent a population of adherent cells that can be isolated from multiple adult tissues. MSCs have immunomodulatory capacity and the ability to differentiate into many cell lines. Research study examines the immunomodulatory properties of MSCs isolated from chorion (CMSCs). Following the stimulation process, it was found that MSCs are capable of immunomodulatory action via the release of bioactive molecules as well as through direct contact with the immune cells. Immunomodulatory potential of the CMSCs was analyzed by modifying proliferative capacity of mitogen-activated lymphocytes. CMSCs and lymphocytes were tested in cell-to-cell contact. Lymphocytes were stained with carboxyfluorescein diacetate succinimidyl ester. Inhibition of the proliferation of activated lymphocytes was observed. Following the co-cultivation, the expression of markers involved in the immune response modulation was assessed. Afterwards, an increase in CMSCs expression of IL-10 was detected. Following the co-cultivation with activated lymphocyte, adhesion molecules CD54 and CD44 in the CMSCs increased. An increase of CD54 expression was observed. The properties of CMSCs, adherence and differentiation ability, were confirmed. The phenotype of CMSCs CD105+, CD90+, CD73+, CD44+, CD29+, CD45−, CD34−, CD54+ was characterized. It was demonstrated that chorion-derived MSCs have important immunomodulatory effects.
Time Series RUL Estimation of Medium Voltage Connectors to Ease Predictive Maintenance Plans
Authors: Gómez-Pau Álvaro , Riba Jordi-Roger , Moreno-Eguilaz Manuel
Published: December 2020

The ageing process of medium voltage power connectors can lead to important power system faults. An on-line prediction of the remaining useful life (RUL) is a convenient strategy to prevent such failures, thus easing the application of predictive maintenance plans. The electrical resistance of the connector is the most widely used health indicator for condition monitoring and RUL prediction, even though its measurement is a challenging task because of its low value, which typically falls in the range of a few micro-ohms. At the present time, the RUL of power connectors is not estimated, since their electrical parameters are not monitored because medium voltage connectors are considered cheap and secondary devices in power systems, despite they play a critical role, so their failure can lead to important power flow interruptions with the consequent safety risks and economic losses. Therefore, there is an imperious need to develop on-line RUL prediction strategies. This paper develops an on-line method to solve this issue, by predicting the RUL of medium voltage connectors based on the degradation trajectory of the electrical resistance, which is characterized by analyzing the electrical resistance time series data by means of the autoregressive integrated moving average (ARIMA) method. The approach proposed in this paper allows applying predictive maintenance plans, since the RUL enables determining when the power connector must be replaced by a new one. Experimental results obtained from several connectors illustrate the feasibility and accuracy of the proposed approach for an on-line RUL prediction of power connectors.
Sustainable and Durable Performance of Pozzolanic Additions to Prevent Alkali-Silica Reaction (ASR) Promoted by Aggregates with Different Reaction Rates
Authors: Menéndez Esperanza , Sanjuán Miguel Ángel , García-Roves Ricardo , Argiz Cristina , Recino Hairon
Published: December 2020

The increased use of industrial wastes and by-products to produce concretes and blended cements is a lever to achieve carbon neutrality. Furthermore, they could improve their durability. Some pozzolanic additions can minimize the alkali-silica reaction (ASR), which is a well-known deleterious process that occurs between some reactive aggregates and the alkaline pore solution found in mortars and concretes. This work quantifies the efficiency of four pozzolanic materials (natural pozzolan, P, siliceous coal fly ash, V, silica fume, D, and blast-furnace slag, S) assessed by means of compressive strength testing, open porosity, ASR-expansion measurements, and SEM microscopy. Accelerated expansion tests were performed in mortar bars with a cement/sand ratio of 1/2.25 and a water/cement ratio of 0.47, two reactive aggregates and a non-reactive one. The major contributions of this paper are: (i) The more aggregate reactivity is, the higher ASR mitigation level was found when additions were added and (ii) The best additions for ASR inhibition are silica fume and fly ash.
On a Viscosity Iterative Method for Solving Variational Inequality Problems in Hadamard Spaces
Authors: Aremu Kazeem Olalekan , Izuchukwu Chinedu , Abass Hammed Anuolwupo , Mewomo Oluwatosin Temitope
Published: December 2020

In this paper, we propose and study an iterative algorithm that comprises of a finite family of inverse strongly monotone mappings and a finite family of Lipschitz demicontractive mappings in an Hadamard space. We establish that the proposed algorithm converges strongly to a common solution of a finite family of variational inequality problems, which is also a common fixed point of the demicontractive mappings. Furthermore, we provide a numerical experiment to demonstrate the applicability of our results. Our results generalize some recent results in literature.
The Potential Role of Hydrogen Sulfide in the Regulation of Cerebrovascular Tone
Authors: Dongó Eleni , Kiss Levente
Published: December 2020

A better understanding of the regulation of cerebrovascular circulation is of great importance because stroke and other cerebrovascular diseases represent a major concern in healthcare leading to millions of deaths yearly. The circulation of the central nervous system is regulated in a highly complex manner involving many local factors and hydrogen sulfide (H2S) is emerging as one such possible factor. Several lines of evidence support that H2S takes part in the regulation of vascular tone. Examinations using either exogenous treatment with H2S donor molecules or alterations to the enzymes that are endogenously producing this molecule revealed numerous important findings about its physiological and pathophysiological role. The great majority of these studies were performed on vessel segments derived from the systemic circulation but there are important observations made using cerebral vessels as well. The findings of these experimental works indicate that H2S is having a complex, pleiotropic effect on the vascular wall not only in the systemic circulation but in the cerebrovascular region as well. In this review, we summarize the most important experimental findings related to the potential role of H2S in the cerebral circulation.
Artificial Intelligence for Modeling Real Estate Price Using Call Detail Records and Hybrid Machine Learning Approach
Authors: Pinter Gergo , Mosavi Amir , Felde Imre
Published: December 2020

Advancement of accurate models for predicting real estate price is of utmost importance for urban development and several critical economic functions. Due to the significant uncertainties and dynamic variables, modeling real estate has been studied as complex systems. In this study, a novel machine learning method is proposed to tackle real estate modeling complexity. Call detail records (CDR) provides excellent opportunities for in-depth investigation of the mobility characterization. This study explores the CDR potential for predicting the real estate price with the aid of artificial intelligence (AI). Several essential mobility entropy factors, including dweller entropy, dweller gyration, workers’ entropy, worker gyration, dwellers’ work distance, and workers’ home distance, are used as input variables. The prediction model is developed using the machine learning method of multi-layered perceptron (MLP) trained with the evolutionary algorithm of particle swarm optimization (PSO). Model performance is evaluated using mean square error (MSE), sustainability index (SI), and Willmott’s index (WI). The proposed model showed promising results revealing that the workers’ entropy and the dwellers’ work distances directly influence the real estate price. However, the dweller gyration, dweller entropy, workers’ gyration, and the workers’ home had a minimum effect on the price. Furthermore, it is shown that the flow of activities and entropy of mobility are often associated with the regions with lower real estate prices.
Portfolio Tail Risk: A Multivariate Extreme Value Theory Approach
Authors: Božović Miloš
Published: December 2020

This paper develops a method for assessing portfolio tail risk based on extreme value theory. The technique applies separate estimations of univariate series and allows for closed-form expressions for Value at Risk and Expected Shortfall. Its forecasting ability is tested on a portfolio of U.S. stocks. The in-sample goodness-of-fit tests indicate that the proposed approach is better suited for portfolio risk modeling under extreme market movements than comparable multivariate parametric methods. Backtesting across multiple quantiles demonstrates that the model cannot be rejected at any reasonable level of significance, even when periods of stress are included. Numerical simulations corroborate the empirical results.
Optimal Design of LLC Resonant DC Transformer under Adaptive Frequency Tracking Strategy
Authors: Tang Yu , Kong Dekai , Duan Chenxu , Sun Hao
Published: December 2020

In recent years, the LLC (inductor–inductor–capacitor) DC transformer has been widely used in communication and computer power supply because of its advantages of zero voltage conduction of primary switch and zero current turn off concerning the output rectifier diode. To obtain higher transmission efficiency and make the LLC DC transformer always run at the optimal operating point, the switching frequency of the LLC DC transformer should work at the resonance frequency of the circuit. In actual conditions, the optimal operating frequency of the LLC DC transformer will be changed due to the influences of the working condition on the circuit parameters and the load change. Therefore, the LLC DC transformer controlled by the fixed frequency mode will not be in the best working condition. In this paper, an adaptive frequency tracking method is used to control the circuit; when the circuit parameters change, the LLC DC transformer can always be in the best working state. Then, the influence of circuit parameters such as output power and excitation inductor on the optimal working point of the LLC DC transformer is analyzed in detail. Finally, a 1 kW LLC resonant converter prototype is designed under laboratory conditions to verify the feasibility of the control strategy.
Hoard or Exploit? Intergenerational Allocation of Exhaustible Natural Resources
Authors: Abu-Kalla Hala , Palatnik Ruslana Rachel , Ayalon Ofira , Shechter Mordechai
Published: December 2020

In this paper, a “general equilibrium” (GE) model was developed for the allocation of exhaustible natural resources to examine the impact of different extraction scenarios on intergenerational economic welfare. A stylized GE model was applied to Israel’s natural gas (NG) market to evaluate economic indicators resulting from NG-extraction scenarios: a baseline scenario based on current policy in the NG sector, a conservative scenario based on a lower extraction rate, and an intensive scenario based on a faster extraction rate. The impact of various resource income-allocation strategies on intergenerational economic welfare was examined through the mechanism of a “sovereign wealth fund” (SWF). The results indicate that a higher NG-extraction rate combined with an appropriate investment strategy for NG profits is preferable from an economic perspective compared to a conservative rate. Investment of the government take from the NG market in research and development (R&D) of renewable electricity production can sustainably increase economic welfare.
In Loop Design of the Coils and the Electromagnetic Shielding Elements for the Wireless Charging Systems
Authors: Frivaldsky Michal , Pavelek Miroslav
Published: December 2020

This paper deals with in loop design of coupling elements of the wireless charging systems (WChS). The in-loop design is created as a script/User Interface (UI) in MATLAB environment, which is based on finite element models of WChS. Main aim of developed tool is to easily identify the optimal geometrical parameters of the coupling coils. The optimization of the coil’s geometrical and electrical parameters is specified by an algorithm, which is based on definition for transfer of required amount of power and on geometrical restrictions of the target application. The second part of the proposed script/UI is used for user guided design of the electromagnetic shielding. It enables to optimize the shielding parameters in order to reach the limits defined by international standards for safety levels with respect to human exposure. Proposed design methodology together with user interface have been verified though experimental validation. For this purpose, construction of WChS was realized based on the results from in loop design process. Comparisons have been made according to the evaluation of simulation model´s accuracy, that is, the values of self-inductances, mutual inductances, coupling coefficient and gain characteristics have been evaluated (simulations vs. experiments). At the end of the paper the evaluation of the shielding performance was realized, while once more the comparison between simulation and experiments have been made. Received results are showing less than 2% of the relative error. Using presented methodology, the fast optimization actions can be done during design and modelling of WChS.
Power Quality Phenomena in Electric Railway Power Supply Systems: An Exhaustive Framework and Classification
Authors: Kaleybar Hamed Jafari , Brenna Morris , Foiadelli Federica , Fazel Seyed Saeed , Zaninelli Dario
Published: December 2020

Electric railway power systems (ERPS) as one of the most critical and high-power end-user loads of utility grids are characterized by outlandish power quality (PQ) problems all over the world. The extension and evolution of different supply topologies for these systems has resulted in significant and various forms of distortions in network voltage and current in all ERPS, the connected power system, and adjacent consumers. During the last years, numerous studies have been offered to investigate various aspects of PQs in a specific supplying topology. Variation in the supply structure of the ERPS and different types of locomotives has propelled the observation of different PQ phenomena. This versatility and development have led to confront considerable types of two-way interactive interfaces as well as reliability and PQ problems in ERPS. In addition, the lack of standards explicitly dedicated to ERPS has added to the ambiguity and complexity of this issue. In this paper, an extensive review of PQ distortions and phenomena in different configurations of ERPS is proposed and a systematic classification is presented. More than 140 scientific papers and publications are studied and categorized which can provide a fast review and a perfect perspective on the status of PQ indexes for researchers and experts.
A Support Vector Machine Learning-Based Protection Technique for MT-HVDC Systems
Authors: Muzzammel Raheel , Raza Ali
Published: December 2020

High voltage direct current (HVDC) transmission systems are suitable for power transfer to meet the increasing demands of bulk energy and encourage interconnected power systems to incorporate renewable energy sources without any fear of loss of synchronism, reliability, and efficiency. The main challenge associated with DC grid protection is the timely diagnosis of DC faults because of its rapid built up, resulting in failures of power electronic circuitries. Therefore, the demolition of HVDC systems is evaded by identification, classification, and location of DC faults within milliseconds (ms). In this research, the support vector machine (SVM)-based protection algorithm is developed so that DC faults could be identified, classified, and located in multi-terminal high voltage direct current (MT-HVDC) systems. A four-terminal HVDC system is developed in Matlab/Simulink for the analysis of DC voltages and currents. Pole to ground and pole to pole faults are applied at different locations and times. Principal component analysis (PCA) is used to extract reduced dimensional features. These features are employed for the training and testing of SVM. It is found from simulations that DC faults are identified, classified, and located within 0.15 ms, ensuring speedy DC grid protection. The realization and practicality of the proposed machine learning algorithm are demonstrated by analyzing more straightforward computations of standard deviation and normalization.
Humidity-Sensitive, Demand-Controlled Ventilation Applied to Multiunit Residential Building—Performance and Energy Consumption in Dfb Continental Climate
Authors: Sowa Jerzy , Mijakowski Maciej
Published: December 2020

Humidity-sensitive, demand-controlled ventilation systems have been in use for many years in regions with oceanic climates. Some attempts have been made to apply this technology in Poland, which has a continental climate. This article evaluates the performance and energy consumption of such a system when applied in an eight-floor, multiunit, residential building, i.e., the virtual reference building described by the National Energy Conservation Agency (NAPE), Poland. Simulations using the computer program CONTAM were performed for the whole heating season based upon the climate in Warsaw. Besides passive stack ventilation, that served as a reference, two ventilation systems were studied: one standard and one “hybrid” system with additional roof fans. This study confirmed that the application of humidity-sensitive, demand-controlled ventilation in multiunit residential buildings in a continental climate (Dfb) led to significant energy savings (up to 11.64 kWh/m2 of primary energy). However, the operation of the system on higher floors was found to be ineffective. Ensuring consistent operation of the system on all floors required supplementary fans. The introduction of a hybrid mode reduced carbon dioxide concentrations by approximately 32% in the units located in the upper part of the building. The energetic effect in such cases depends strongly on the electricity source. In the case of the national energy grid, savings of primary energy would be relatively low, i.e., 1.07 kWh/m2, but in the case of locally produced renewable energy, the energy savings would be equal to 5.18 kWh/m2.
The Effect of Aggressive Driving on Vehicle Parameters
Authors: Szumska Emilia M. , Jurecki Rafał
Published: December 2020

Driver behavior is one of the most relevant factors affecting road safety. Many traffic situations require a driver to be able to recognize possible danger. In numerous works, aggressive driving is understood as unsafe and as a hazard entailing the risk of potential crashes. However, traffic safety is not the only thing affected by a vehicle operator’s driving style. A driver’s behavior also impacts the operating costs of a vehicle and the emission of environmental air pollutants. This is confirmed by numerous works devoted to the examination of the effect of driving style on fuel economy and air pollution. The objective of this study was to investigate the influence of aggressive driving on fuel consumption and emission of air pollutants. The simulation was carried out based on real velocity profiles collected in real-world tests under urban and motorway driving conditions. The results of simulations confirm that an aggressive driving style causes a significant increase in both fuel consumption and emission of air pollutants. This is particularly apparent in urban test cycles, where an aggressive driving style results in higher average fuel consumption and in pollutant emissions as much as 30% to 40% above the average compared to calm driving.
Evaluation of Synergies in the Context of European Multi-Business Utilities
Authors: Fuhrmann Jens , Madlener Reinhard
Published: December 2020

In this paper, we evaluate selected multi-business utilities in the European energy market with regard to synergy potentials. To this end, we survey the development of the energy market in Europe and the performance of integrated versus focused utilities regarding their capital market performance measured by their corporate surplus (or deficit). The analysis is restricted to true business integration, in contrast to horizontal or vertical cooperation among separate firms. The German utility company RWE is analyzed in more detail. We find that, over the last 10–15 years, most of the multi-business utilities investigated underperformed compared to more focused utilities, and that they were even below the STOXX Europe 600 utilities index. Furthermore, synergy potentials need to be evaluated continuously, especially when influencing factors, with the potential to act as “game changers”, are either emerging on the horizon or are already present. We conclude that operating an integrated business model is not necessarily outdated in today’s energy markets, and offers a number of advantages.
The Effect of Social Capital on Environmental Pollution in China—Suppression or Promotion?
Authors: Wang Yuxin , Xiong Jinping , Li Wenlong , Na Ming , Yao Mei
Published: December 2020

The 19th National Congress of the Communist Party of China clearly regards the prevention and control of environmental pollution as one of the “three key battles” to build a well-off society. This paper analyzes the relationship between social capital and environmental pollution from both theoretical and empirical perspectives. From the theoretical perspective, social capital has two opposite effects on environmental pollution: the suppression and the promotion. The former indicates that the improvement of social capital level reduces the cost of residents’ boycott to pollution and reduces pollution emissions, while the latter manifests that the improvement of social capital worsens environmental pollution due to the ability of polluting enterprises to withstand residents’ boycott. Based on the panel data of China from 2008 to 2016, the empirical results show that social capital has inverted U-shaped characteristics on environmental pollution. Low level of social capital will increase pollution emissions and only when social capital reaches a certain level can it be beneficial to environmental protection. This paper attempts to better understand the functions of social capital in environmental governance and provides constructive proposals on how to exert the governance role of social capital on environmental protection for policy makers. Regions with higher levels of social capital should exert the suppression effect of social capital and regions with low levels should focus on improving the level of social capital, while formal regulation means shall be adopted to control pollution.
Improving Aboriginal Maternal Health by Strengthening Connection to Culture, Family and Community
Authors: Wyndow Paula , Clifton Elaine , Walker Roz
Published: December 2020

(1) Background: To explore the function of smoking in Aboriginal women’s lives from a trauma-informed, women-centred approach in order to inform the design of a culturally meaningful smoking cessation program for women living in the Pilbara, Western Australia; (2) Methods: Qualitative and Community Based Participatory Action Research (CBPAR) was used to discover what Aboriginal women know about smoking, the specific contextual issues that influence their smoking, and what community supports are available to help them quit smoking. Inductive analysis was used to determine key themes; (3) Results: 25 Aboriginal women (smokers, non-smokers, and ex-smokers) participated in focus groups or individual interviews. Women smoked to deal with stress, trauma and for maintaining social connections. Women who stopped smoking did so on their own when the reason was important enough or when they saw alternative ways of living. Creating safe places to bring women together to yarn about women’s business and link with health services was identified as critical to support women to stop smoking. Conclusions: Strategies to address smoking need to bring community, culture and health together in a meaningful way for women and their families; build on existing community strengths; and educate communities about the effects of smoking, and health professionals about how to support women to stop smoking.
The Effects of an Artificial Garden on Heart Rate Variability among Healthy Young Japanese Adults
Authors: Suenaga Hiromi , Murakami Kanako , Murata Nozomi , Nishikawa Syoriki , Tsutsumi Masae , Nogaki Hiroshi
Published: December 2020

Spending time in nature might positively influence mental health by inducing a relaxed state. Recently, gardens have been created on hospital rooftops in Japan to help inpatients recover from various physical and mental aliments. However, there is little evidence regarding any positive physiological effects of artificial gardens designed for health. The purpose of this study was to assess the psychological and cardiovascular responses incited by artificial natural environments. Japanese university students (n = 38) participated in a one-group pretest post-test experiment conducted at the Yamaguchi Flower Expo in Japan in October 2018, designed to assess whether exposure to four environments (forest, flowers, ocean, and artificial garden for health) influenced heart rate variability measures. After pretesting to determine baseline measurements, participants completed a circuit through the four natural environments. Following circuit completion, post-testing determined that the low frequency/high frequency ratio was significantly lower in the overall sample and the four areas had similar influences on heart rate variability. Findings suggest that exposure to nature by walking through natural areas and in rooftop artificial gardens might enhance the balance between the sympathetic and parasympathetic nervous systems.
Disparities in Risks of Malaria Associated with Climatic Variability among Women, Children and Elderly in the Chittagong Hill Tracts of Bangladesh
Authors: Emeto Theophilus I. , Adegboye Oyelola A. , Rumi Reza A. , Khan Mahboob-Ul I. , Adegboye Majeed , Khan Wasif A. , Rahman Mahmudur , Streatfield Peter K. , Rahman Kazi M.
Published: December 2020

Malaria occurrence in the Chittagong Hill Tracts in Bangladesh varies by season and year, but this pattern is not well characterized. The role of environmental conditions on the occurrence of this vector-borne parasitic disease in the region is not fully understood. We extracted information on malaria patients recorded in the Upazila (sub-district) Health Complex patient registers of Rajasthali in Rangamati district of Bangladesh from February 2000 to November 2009. Weather data for the study area and period were obtained from the Bangladesh Meteorological Department. Non-linear and delayed effects of meteorological drivers, including temperature, relative humidity, and rainfall on the incidence of malaria, were investigated. We observed significant positive association between temperature and rainfall and malaria occurrence, revealing two peaks at 19 °C (logarithms of relative risks (logRR) = 4.3, 95% CI: 1.1–7.5) and 24.5 °C (logRR = 4.7, 95% CI: 1.8–7.6) for temperature and at 86 mm (logRR = 19.5, 95% CI: 11.7–27.3) and 284 mm (logRR = 17.6, 95% CI: 9.9–25.2) for rainfall. In sub-group analysis, women were at a much higher risk of developing malaria at increased temperatures. People over 50 years and children under 15 years were more susceptible to malaria at increased rainfall. The observed associations have policy implications. Further research is needed to expand these findings and direct resources to the vulnerable populations for malaria prevention and control in the Chittagong Hill Tracts of Bangladesh and the region with similar settings.
The Business Sector, Firm Age, and Performance: The Mediating Role of Foreign Ownership and Financial Leverage
Authors: Mallinguh Edmund , Wasike Christopher , Zoltan Zeman
Published: December 2020

The paper explores the business sector and firm age effects on firm performance mediated by foreign ownership levels in domestic firms and financial leverage by examining 146 Medium Enterprises (MEs). The results show that except for ownership, the business sector, firm age, foreign ownership level, and financial leverage significantly influence performance. Foreign ownership substantially mediates the correlation between firm age and performance but not leverage. Both foreign ownership and leverage have no substantial mediating effect on the relationship between the business sector and financial performance. Moreover, the findings reveal business sectors whose performance is statistically different from zero based on the referent group.
Prophylactic Therapy with Human Amniotic Fluid Stem Cells Improves Long-Term Cognitive Impairment in Rat Neonatal Sepsis Survivors
Authors: Abe Yushi , Ochiai Daigo , Sato Yu , Kanzaki Seiji , Ikenoue Satoru , Kasuga Yoshifumi , Tanaka Mamoru
Published: December 2020

A systemic inflammatory response induces multiple organ dysfunction and results in poor long-term neurological outcomes in neonatal sepsis. However, there is no effective therapy for treating or preventing neonatal sepsis besides antibiotics and supportive care. Therefore, a novel strategy to improve neonatal sepsis-related morbidity and mortality is desirable. Recently, we reported that prophylactic therapy with human amniotic stem cells (hAFSCs) improved survival in a rat model of lipopolysaccharide (LPS)-induced neonatal sepsis through immunomodulation. Besides improving the mortality, increasing survival without major morbidities is an important goal of neonatal intensive care for neonatal sepsis. This study investigated long-term neurological outcomes in neonatal sepsis survivors treated with hAFSCs using the LPS-induced neonatal sepsis model in rats. We found that prophylactic therapy with hAFSCs improved spatial awareness and memory-based behavior in neonatal sepsis survivors at adolescence in rats. The treatment suppressed acute reactive gliosis and subsequently reduced astrogliosis in the hippocampal region over a long period of assessment. To the best of our knowledge, this is the first report that proves the concept that hAFSC treatment improves cognitive impairment in neonatal sepsis survivors. We demonstrate the efficacy of hAFSC therapy in improving the mortality and morbidity associated with neonatal sepsis.
BET-Inhibitor I-BET762 and PARP-Inhibitor Talazoparib Synergy in Small Cell Lung Cancer Cells
Authors: Fiorentino Francesco Paolo , Marchesi Irene , Schröder Christoph , Schmidt Ronny , Yokota Jun , Bagella Luigi
Published: December 2020

Small cell lung cancer (SCLC) is an aggressive type of lung cancer with high mortality that is caused by frequent relapses and acquired resistance. Despite that several target-based approaches with potential therapeutic impact on SCLC have been identified, numerous targeted drugs have not been successful in providing improvements in cancer patients when used as single agents. A combination of targeted therapies could be a strategy to induce maximum lethal effects on cancer cells. As a starting point in the development of new drug combination strategies for the treatment of SCLC, we performed a mid-throughput screening assay by treating a panel of SCLC cell lines with BETi or AKi in combination with PARPi or EZH2i. We observed drug synergy between I-BET762 and Talazoparib, BETi and PARPi, respectively, in SCLC cells. Combinatorial efficacy was observed in MYCs-amplified and MYCs-wt SCLC cells over SCLC cells with impaired MYC signaling pathway or non-tumor cells. We indicate that drug synergy between I-BET762 and Talazoparib is associated with the attenuation HR-DSBR process and the downregulation of various players of DNA damage response by BET inhibition, such as CHEK2, PTEN, NBN, and FANCC. Our results provide a rationale for the development of new combinatorial strategies for the treatment of SCLC.
Small Molecules Acting on Myofilaments as Treatments for Heart and Skeletal Muscle Diseases
Authors: Alsulami Khulud , Marston Steven
Published: December 2020

Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are the most prevalent forms of the chronic and progressive pathological condition known as cardiomyopathy. These diseases have different aetiologies; however, they share the feature of haemodynamic abnormalities, which is mainly due to dysfunction in the contractile proteins that make up the contractile unit known as the sarcomere. To date, pharmacological treatment options are not disease-specific and rather focus on managing the symptoms, without addressing the disease mechanism. Earliest attempts at improving cardiac contractility by modulating the sarcomere indirectly (inotropes) resulted in unwanted effects. In contrast, targeting the sarcomere directly, aided by high-throughput screening systems, could identify small molecules with a superior therapeutic value in cardiac muscle disorders. Herein, an extensive literature review of 21 small molecules directed to five different targets was conducted. A simple scoring system was created to assess the suitability of small molecules for therapy by evaluating them in eight different criteria. Most of the compounds failed due to lack of target specificity or poor physicochemical properties. Six compounds stood out, showing a potential therapeutic value in HCM, DCM or heart failure (HF). Omecamtiv Mecarbil and Danicamtiv (myosin activators), Mavacamten, CK-274 and MYK-581 (myosin inhibitors) and AMG 594 (Ca2+-sensitiser) are all small molecules that allosterically modulate troponin or myosin. Omecamtiv Mecarbil showed limited efficacy in phase III GALACTIC-HF trial, while, results from phase III EXPLORER-HCM trial were recently published, indicating that Mavacamten reduced left ventricular outflow tract (LVOT) obstruction and diastolic dysfunction and improved the health status of patients with HCM. A novel category of small molecules known as “recouplers” was reported to target a phenomenon termed uncoupling commonly found in familial cardiomyopathies but has not progressed beyond preclinical work. In conclusion, the contractile apparatus is a promising target for new drug development.
Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events
Authors: Barbalata Teodora , Moraru Oriana E. , Stancu Camelia S. , Devaux Yvan , Simionescu Maya , Sima Anca V. , Niculescu Loredan S.
Published: December 2020

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.
Dual Function Molecules and Processes in Cell Fate Decision: A Preface to the Special Issue
Authors: Emanuele Sonia , Giuliano Michela
Published: December 2020

A lot of water has passed under the bridge since 1999, when C [...]
Functional Complexes of Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Receptors: Expression in Adult but Not Fetal Lung Tissue
Authors: Franco Rafael , Lillo Alejandro , Rivas-Santisteban Rafael , Rodríguez-Pérez Ana , Reyes-Resina Irene , Labandeira-García José , Navarro Gemma
Published: December 2020

Angiotensin-converting enzyme 2 (ACE2) is a membrane peptidase and a component of the renin-angiotensin system (RAS) that has been found in cells of all organs, including the lungs. While ACE2 has been identified as the receptor for severe acute respiratory syndrome (SARS) coronaviruses, the mechanism underlying cell entry remains unknown. Human immunodeficiency virus infects target cells via CXC chemokine receptor 4 (CXCR4)-mediated endocytosis. Furthermore, CXCR4 interacts with dipeptidyl peptidase-4 (CD26/DPPIV), an enzyme that cleaves CXCL12/SDF-1, which is the chemokine that activates this receptor. By analogy, we hypothesized that ACE2 might also be capable of interactions with RAS-associated G-protein coupled receptors. Using resonance energy transfer and cAMP and mitogen-activated protein kinase signaling assays, we found that human ACE2 interacts with RAS-related receptors, namely the angiotensin II type 1 receptor (AT1R), the angiotensin II type 2 receptor (AT2R), and the MAS1 oncogene receptor (MasR). Although these interactions led to various alterations of signal transduction, but, more importantly, ligand binding to AT1R resulted in the downregulation of ACE2 cell surface expression, while ligand binding to AT2R, but not to MasR, resulted in upregulation of ACE2 cell surface expression. Proximity ligation assays performed in situ revealed macromolecular complexes containing ACE2 and AT1R, AT2R or MasR in adult but not fetal mouse lung tissue. These findings highlight the relevance of RAS in SARS-CoV-2 infection and the role of ACE2-containing complexes as potential therapeutic targets.
The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases
Authors: Todd Alison C. , Hardingham Giles E.
Published: December 2020

The astrocytic glutamate transporters excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2) play a key role in nervous system function to maintain extracellular glutamate levels at low levels. In physiology, this is essential for the rapid uptake of synaptically released glutamate, maintaining the temporal fidelity of synaptic transmission. However, EAAT1/2 hypo-expression or hypo-function are implicated in several disorders, including epilepsy and neurodegenerative diseases, as well as being observed naturally with aging. This not only disrupts synaptic information transmission, but in extremis leads to extracellular glutamate accumulation and excitotoxicity. A key facet of EAAT1/2 expression in astrocytes is a requirement for signals from other brain cell types in order to maintain their expression. Recent evidence has shown a prominent role for contact-dependent neuron-to-astrocyte and/or endothelial cell-to-astrocyte Notch signalling for inducing and maintaining the expression of these astrocytic glutamate transporters. The relevance of this non-cell-autonomous dependence to age- and neurodegenerative disease-associated decline in astrocytic EAAT expression is discussed, plus the implications for disease progression and putative therapeutic strategies.
Adiponectin Exerts Peripheral Inhibitory Effects on the Mouse Gastric Smooth Muscle through the AMPK Pathway
Authors: Idrizaj Eglantina , Garella Rachele , Nistri Silvia , Dell’Accio Alfonso , Cassioli Emanuele , Rossi Eleonora , Castellini Giovanni , Ricca Valdo , Squecco Roberta , Baccari Maria Caterina
Published: December 2020

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach. The mechanical results showed that ADPN caused a decay of the strip basal tension, which was abolished by the nitric oxide (NO) synthesis inhibitor, L-NG-nitro arginine (L-NNA). The electrophysiological experiments confirmed that all ADPN effects were abolished by L-NNA, except for the reduction of Ca2+ current, which was instead prevented by the inhibitor of AMP-activated protein kinase (AMPK), dorsomorphin. The activation of the AMPK signaling by ADPN was confirmed by immunofluorescence analysis, which also revealed the ADPN R1 receptor (AdipoR1) expression in glial cells of the myenteric plexus. In conclusion, our results indicate that ADPN exerts an inhibitory action on the gastric smooth muscle by acting on AdipoR1 and involving the AMPK signaling pathway at the peripheral level. These findings provide novel bases for considering AMPK as a possible pharmacologic target for the potential treatment of obesity and eating disorders.
Whole Body 3.0 T Magnetic Resonance Imaging in Lymphomas: Comparison of Different Sequence Combinations for Staging Hodgkin’s and Diffuse Large B Cell Lymphomas
Authors: Latifoltojar Arash , Duncan Mark K. J. , Klusmann Maria , Sidhu Harbir , Bainbridge Alan , Neriman Deena , Fraioli Francesco , Lambert Jonathan , Ardeshna Kirit M. , Punwani Shonit
Published: December 2020

To investigate the diagnostic value of different whole-body magnetic resonance imaging (WB-MRI) protocols for staging Hodgkin and diffuse-large B-cell lymphomas (HL and DLBCL), twenty-two patients (M/F 12/10, median age 32, range 22–87, HL/DLBCL 14/8) underwent baseline WB-MRI and 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) fused with computed tomography (CT) scan 18F-FDG-PET-CT. The 3.0 T WB-MRI was performed using pre-contrast modified Dixon (mDixon), T2-weighted turbo-spin-echo (TSE), diffusion-weighted-imaging (DWI), dynamic-contrast-enhanced (DCE) liver/spleen, contrast-enhanced (CE) lung MRI and CE whole-body mDixon. WB-MRI scans were divided into: (1) “WB-MRI DWI+IP”: whole-body DWI + in-phase mDixon (2) “WB-MRI T2-TSE”: whole-body T2-TSE (3) “WB-MRI Post-C”: whole-body CE mDixon + DCE liver/spleen and CE lung mDixon (4) “WB-MRI All “: the entire protocol. Two radiologists evaluated WB-MRIs at random, independently and then in consensus. Two nuclear-medicine-physicians reviewed 18F-FDG PET-CT in consensus. An enhanced-reference-standard (ERS) was derived using all available baseline and follow-up imaging. The sensitivity and specificity of WB-MRI protocols for nodal and extra-nodal staging was derived against the ERS. Agreement between the WB-MRI protocols and the ERS for overall staging was assessed using kappa statistic. For consensus WB-MRI, the sensitivity and specificity for nodal staging were 75%, 98% for WB-MRI DWI+IP, 76%, 98% for WB-MRI Post-C, 83%, 99% for WB-MRI T2-TSE and 87%, 100% for WB-MRI All. The sensitivity and specificity for extra-nodal staging were 67% 100% for WB-MRI DWI+IP, 89%, 100% for WB-MRI Post-C, 89%, 100% for WB-MRI T2-TSE and 100%, 100% for the WB-MRI All. The consensus WB-MRI All read had perfect agreement with the ERS for overall staging [kappa = 1.00 (95% CI: 1.00-1.00)]. The best diagnostic performance is achieved combining all available WB-MRI sequences.
VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions
Authors: Gong Eun-Yeung , Jo Hyung Ah , Park Sang Hyun , Cha Dae Ryong , Hur Dae Young , Han Sang Youb
Published: December 2020

High glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal transition (EMT) has been reported in several diseases, little is known about its relationship with VSIG4 under diabetic conditions. This study aimed to investigate the role of VSIG4 in human tubule cells stimulated by high glucose (HG, 55 mM). HG upregulated both mRNA and protein levels of VSIG4 in proximal tubule cells (HK-2 cells) and Madin Darby Canine Kidney cells. These upregulations were accompanied by increased expression of mesenchymal markers such as fibronectin, N-cadherin, matrix metalloproteinase 9, and vimentin, and by decreased expression of the epithelial marker, E-cadherin. The siRNA-mediated inhibition of VSIG4 in HK-2 cells restored the dysregulation of EMT in cells. Interestingly, VSIG4 inhibition did not affect the expression of transforming growth factor (TGF)-β, whereas inhibition of TGF-β reduced VSIG4 expression, subsequently suppressing fibrosis markers. These findings suggest that VSIG4 plays an important role in mediating renal tubular EMT through the downstream action of HG-induced TGF-β activation.
Complete Extraction of Amorphous Aluminosilicate from Coal Fly Ash by Alkali Leaching under Atmospheric Pressure
Authors: Shoppert Andrei , Valeev Dmitry , Loginova Irina , Chaikin Leonid
Published: December 2020

One of the potential sources of alumina and mesoporous silica is the coal-fired thermal plants waste known as the coal fly ash (CFA). The studies of the alumina extraction from CFA are often focused on the preliminary desilication, but the efficiency of the alkali desilication is low due to formation of the desilication product—Na6[Al6Si6O24]·Na2X (DSP). This research is focused on the possibility of CFA desilication without formation of DSP using a leaching process with higher liquid to solid ratios (L/S) and alkali concentrations. The experimental data were analyzed using an artificial neural network (ANN) machine learning method and a shrinking core model (SCM). The investigation of the CFA morphology, chemical and phase composition before and after leaching were carried out by scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), inductively coupled plasma optical emission spectrometry (ICP-OES) and X-ray diffraction (XRD). The present work shows that it is possible to avoid formation of DSP if using the L/S ratio >20 and concentration of Na2O—400 g/L during CFA leaching. The kinetics analysis by SCM showed that the process is limited by the surface chemical reaction at T <100 °C, and by diffusion through the product layer at T >100 °C, respectively. The SEM images of the solid residue after NaOH leaching under conditions that prevent the DSP formation show mullite particles with an acicular structure.