bluuebunny/crossref_metadata_2025 huggingface dataset:
Al2O3 and Pt Atomic Layer Deposition for Surface Modification of NiTi Shape Memory Films
Authors: Vokoun David , Klimša Ladislav , Vetushka Aliaksei , Duchoň Jan , Racek Jan , Drahokoupil Jan , Kopeček Jaromír , Yu Yo-Shane , Koothan Narmatha , Kei Chi-Chung
Published: July 2020

Pt coatings on NiTi film micro-actuators and/or sensors can add some useful properties, e.g., they may improve the NiTi anticorrosion and thermomechanical characteristics or activate surface properties beneficial for a specific application (e.g., functionalized surfaces for biomedical applications). Pt coatings prepared via atomic layer deposition (ALD) may help reduce cost due to the nanometric thickness. However, no authors have reported preparation of Pt ALD coatings on NiTi films, perhaps due to the challenge of the concurrent NiTi film oxidation during the Pt ALD process. In the present study, Al2O3 and Pt ALD coatings were applied to NiTi thin films. The ALD coating properties were studied using electron and atomic force microscopies and X-ray photoelectron spectroscopy (XPS). Potential structural changes of NiTi due to the ALD process were evaluated using electron microscopy and X-ray diffraction. The presented ALD process resulted in well-controllable preparation of Pt nanoparticles on ultrathin Al2O3 seed layer and a change of the transformation temperatures of the NiTi films.
Cation Doping Approach for Nanotubular Hydrosilicates Curvature Control and Related Applications
Authors: Krasilin Andrei A. , Khrapova Ekaterina K. , Maslennikova Tatiana P.
Published: July 2020

The past two decades have been marked by an increased interest in the synthesis and the properties of geoinspired hydrosilicate nanoscrolls and nanotubes. The present review considers three main representatives of this group: halloysite, imogolite and chrysotile. These hydrosilicates have the ability of spontaneous curling (scrolling) due to a number of crystal structure features, including the size and chemical composition differences between the sheets, (or the void in the gibbsite sheet and SiO2 tetrahedron, in the case of imogolite). Mineral nanoscrolls and nanotubes consist of the most abundant elements, like magnesium, aluminium and silicon, accompanied by uncontrollable amounts of impurities (other elements and phases), which hinder their high technology applications. The development of a synthetic approach makes it possible to not only to overcome the purity issues, but also to enhance the chemical composition of the nanotubular particles by controllable cation doping. The first part of the review covers some principles of the cation doping approach and proposes joint criteria for the semiquantitative prediction of morphological changes that occur. The second part focuses on some doping-related properties and applications, such as morphological control, uptake and release, magnetic and mechanical properties, and catalysis.
Home-Based Functional Electrical Stimulation of Human Permanent Denervated Muscles: A Narrative Review on Diagnostics, Managements, Results and Byproducts Revisited 2020
Authors: Kern Helmut , Carraro Ugo
Published: July 2020

Spinal cord injury (SCI) produces muscle wasting that is especially severe after complete and permanent damage of lower motor neurons, as can occur in complete conus and cauda equina syndrome. Even in this worst-case scenario, mass and function of permanently denervated quadriceps muscle can be rescued by surface functional electrical stimulation using a purpose designed home-based rehabilitation strategy. Early diagnostics is a key factor in the long-term success of this management. Function of quadriceps muscle was quantitated by force measurements. Muscle gross cross-sections were evaluated by quantitative color computed tomography (CT) and muscle and skin biopsies by quantitative histology, electron microscopy, and immunohistochemistry. Two years of treatment that started earlier than 5 years from SCI produced: (a) an increase in cross-sectional area of stimulated muscles; (b) an increase in muscle fiber mean diameter; (c) improvements in ultrastructural organization; and (d) increased force output during electrical stimulation. Improvements are extended to hamstring muscles and skin. Indeed, the cushioning effect provided by recovered tissues is a major clinical benefit. It is our hope that new trials start soon, providing patients the benefits they need.
Efficient Bone Metastasis Diagnosis in Bone Scintigraphy Using a Fast Convolutional Neural Network Architecture
Authors: Papandrianos Nikolaos , Papageorgiou Elpiniki , Anagnostis Athanasios , Papageorgiou Konstantinos
Published: July 2020

(1) Background: Bone metastasis is among diseases that frequently appear in breast, lung and prostate cancer; the most popular imaging method of screening in metastasis is bone scintigraphy and presents very high sensitivity (95%). In the context of image recognition, this work investigates convolutional neural networks (CNNs), which are an efficient type of deep neural networks, to sort out the diagnosis problem of bone metastasis on prostate cancer patients; (2) Methods: As a deep learning model, CNN is able to extract the feature of an image and use this feature to classify images. It is widely applied in medical image classification. This study is devoted to developing a robust CNN model that efficiently and fast classifies bone scintigraphy images of patients suffering from prostate cancer, by determining whether or not they develop metastasis of prostate cancer. The retrospective study included 778 sequential male patients who underwent whole-body bone scans. A nuclear medicine physician classified all the cases into three categories: (a) benign, (b) malignant and (c) degenerative, which were used as gold standard; (3) Results: An efficient and fast CNN architecture was built, based on CNN exploration performance, using whole body scintigraphy images for bone metastasis diagnosis, achieving a high prediction accuracy. The results showed that the method is sufficiently precise when it comes to differentiate a bone metastasis case from other either degenerative changes or normal tissue cases (overall classification accuracy = 91.61% ± 2.46%). The accuracy of prostate patient cases identification regarding normal, malignant and degenerative changes was 91.3%, 94.7% and 88.6%, respectively. To strengthen the outcomes of this study the authors further compared the best performing CNN method to other popular CNN architectures for medical imaging, like ResNet50, VGG16, GoogleNet and MobileNet, as clearly reported in the literature; and (4) Conclusions: The remarkable outcome of this study is the ability of the method for an easier and more precise interpretation of whole-body images, with effects on the diagnosis accuracy and decision making on the treatment to be applied.
Robustness Analysis of the Estimators for the Nonlinear System Identification
Authors: Jakowluk Wiktor , Godlewski Karol
Published: July 2020

The main objective of the system identification is to deliver maximum information about the system dynamics, while still ensuring an acceptable cost of the identification experiment. The focus of such an idea is to design an appropriate experiment so that the departure from normal working conditions during the identification task is minimized. In this paper, the adaptive filtering (AF) scheme for plant model parameter estimation is proposed. The experimental results are obtained using the nonlinear interacting water tanks system. The adaptive filtering is expressed by minimizing the error between the system and the plant model outputs subject to the white noise signal affecting system output. This measurement error is quantified by the comparison of Minimum Error Entropy Renyi (MEER), Least Entropy Like (LEL), Least Squares (LS), and Least Absolute Deviation (LAD) estimators, respectively. The plant model parameters were obtained using sequential quadratic programming (SQP) algorithm. The robustness tests for the double-tank water system parameter estimators are performed using the ellipsoidal confidence regions. The effectiveness analysis for the above-mentioned estimators relies on the total number of iterations and the number of function evaluation comparisons. The main contribution of this paper is the evaluation of different estimation methods for the nonlinear system identification using various excitation signals. The proposed empirical study is illustrated by the numerical examples, and the simulation results are discussed.
Entropic Uncertainty in Spin XY Model with Long-Range Interactions
Authors: Zidan Nour
Published: July 2020

The behavior of the uncertainty relations and their tightness for a system, consisting of two qubits interacting thermally with a magnetic field in the presence of Dzyaloshinskii–Moriya interaction, is discussed, where different types of interaction strengths are considered. It is shown that both coupling and the magnetic field parameters decay the degree of entanglement, and increasing the uncertainty relations and the degree of mixedness. The phenomena of the sudden changes in the investigated quantities are depicted at large values of the field and coupling parameters. Concerning the type of the coupling parameters, distance and the trigonometric coupling have a clear effect on the behavior of the studied physical quantities.
Optic Disc Segmentation Using Attention-Based U-Net and the Improved Cross-Entropy Convolutional Neural Network
Authors: Jin Baixin , Liu Pingping , Wang Peng , Shi Lida , Zhao Jing
Published: July 2020

Medical image segmentation is an important part of medical image analysis. With the rapid development of convolutional neural networks in image processing, deep learning methods have achieved great success in the field of medical image processing. Deep learning is also used in the field of auxiliary diagnosis of glaucoma, and the effective segmentation of the optic disc area plays an important assistant role in the diagnosis of doctors in the clinical diagnosis of glaucoma. Previously, many U-Net-based optic disc segmentation methods have been proposed. However, the channel dependence of different levels of features is ignored. The performance of fundus image segmentation in small areas is not satisfactory. In this paper, we propose a new aggregation channel attention network to make full use of the influence of context information on semantic segmentation. Different from the existing attention mechanism, we exploit channel dependencies and integrate information of different scales into the attention mechanism. At the same time, we improved the basic classification framework based on cross entropy, combined the dice coefficient and cross entropy, and balanced the contribution of dice coefficients and cross entropy loss to the segmentation task, which enhanced the performance of the network in small area segmentation. The network retains more image features, restores the significant features more accurately, and further improves the segmentation performance of medical images. We apply it to the fundus optic disc segmentation task. We demonstrate the segmentation performance of the model on the Messidor dataset and the RIM-ONE dataset, and evaluate the proposed architecture. Experimental results show that our network architecture improves the prediction performance of the base architectures under different datasets while maintaining the computational efficiency. The results render that the proposed technologies improve the segmentation with 0.0469 overlapping error on Messidor.
An Entropy-Based Approach for Anomaly Detection in Activities of Daily Living in the Presence of a Visitor
Authors: Howedi Aadel , Lotfi Ahmad , Pourabdollah Amir
Published: July 2020

This paper presents anomaly detection in activities of daily living based on entropy measures. It is shown that the proposed approach will identify anomalies when there are visitors representing a multi-occupant environment. Residents often receive visits from family members or health care workers. Therefore, the residents’ activity is expected to be different when there is a visitor, which could be considered as an abnormal activity pattern. Identifying anomalies is essential for healthcare management, as this will enable action to avoid prospective problems early and to improve and support residents’ ability to live safely and independently in their own homes. Entropy measure analysis is an established method to detect disorder or irregularities in many applications: however, this has rarely been applied in the context of activities of daily living. An experimental evaluation is conducted to detect anomalies obtained from a real home environment. Experimental results are presented to demonstrate the effectiveness of the entropy measures employed in detecting anomalies in the resident’s activity and identifying visiting times in the same environment.
DPsim—Advancements in Power Electronics Modelling Using Shifted Frequency Analysis and in Real-Time Simulation Capability by Parallelization
Authors: Mirz Markus , Dinkelbach Jan , Monti Antonello
Published: July 2020

Real-time simulation is an increasingly popular tool for product development and research in power systems. However, commercial simulators are still quite exclusive due to their costs and they face problems in bridging the gap between two common types of power system simulation, conventional phasor based, and electromagnetic transient simulation. This work describes recent improvements to the open source real-time simulator DPsim to address increasingly important use cases that involve power electronics that are connected to the electrical grid and increasing grid sizes. New power electronic models have been developed and integrated into the DPsim simulator together with techniques to decouple the system solution, which facilitate parallelization. The results show that the dynamic phasors in DPsim, which result from shifted frequency analysis, allow the user to combine the characteristics of conventional phasor and electromagnetic transient simulation. Besides, simulation speed up techniques that are known from the electromagnetic domain and new techniques, specific to dynamic phasors, significantly improve the performance. It demonstrates the advantages of dynamic phasor simulation for future power systems and the applicability of this concept to large scale scenarios.
Physicochemical Composition Variability and Hydraulic Conditions in a Geothermal Borehole—The Latest Study in Podhale Basin, Poland
Authors: Operacz Agnieszka , Bielec Bogusław , Tomaszewska Barbara , Kaczmarczyk Michał
Published: July 2020

In deep geothermal boreholes, an effect of temperature (so-called thermal lift) is observed, which results in the volumetric expansion of the fluid extracted. This process results in increased wellhead pressure values being recorded; in the absence of an appropriate correction, hydraulic properties of the reservoir layer cannot be properly determined. As an example of this effect, the Chochołów PIG-1 (CH PIG-1) geothermal borehole situated in Podhale Basin in Poland was used. Hydrodynamic tests including two pumping phases were carried out in the well in order to establish the basic hydraulic properties related to the determination of its operational resources (maximum water extraction value–capacity) and permissible groundwater level. Particular attention was paid to the thermal lift effect in the borehole. The conductivity, which depends on the pumping level, could be two to three times higher with temperature correction than results without any correction. The goal was to analyse the variability of the observed physiochemical properties of the exploited geothermal waters and to determine the correlation between the properties analysed and the temperature of the geothermal water. For the relationship between temperature and the observed pressure at the wellhead, the value of the correlation coefficient was negative (a negative linear relationship was determined), which means that as the temperature increases, the wellhead pressure decreases. The hydrodynamic tests carried out in the CH PIG-1 borehole and the analysis of variability of selected ions and parameters in exploited water were necessary to assess the possibility of increasing the efficiency (Q) of the CH PIG-1 borehole and to determine the water quality and its natural variability. Such information is crucial for the functioning of the recreational complex based on the use of geothermal water. A study of the phenomena affecting the exploitation of hot water from deep boreholes enables their effective exploitation and the use of resources in accordance with the expectations of investors.
A Sliding-Mode-Based Duty Ratio Controller for Multiple Parallelly-Connected DC–DC Converters with Constant Power Loads on MVDC Shipboard Power Systems
Authors: Du Wenzeng , Yang Genke , Pan Changchun , Xi Peifeng , Chen Yue
Published: July 2020

The development of powered electronic technology has made many aware of the design and control of ship power systems (SPSs), and has made medium voltage DC (MVDC) architecture the main research direction in the future. The negative impedance characteristic of constant power load (CPL) generated by the coupling of powered electronic converters will seriously affect the stability of the systems if these converters are not properly controlled. The conventional linear control method can only guarantee the small-signal stability of the system near its equilibrium point. When the operating point changes in a large range, linear control methods will be ineffective. More importantly, research for the large-signal stability of the multi-converter system with CPLs is still rarely involved. In this paper, a sliding-mode-based duty ratio controller (SMDC) is proposed for voltage regulation and current sharing of the multiple parallelly-connected DC–DC converters system loaded by CPLs. By controlling the output voltage of each converter with SMDC, large-signal stability of the coupled bus voltage is ensured. Meanwhile, proportional current sharing between the parallel converters is achieved by droop control integrated in the reference value of converter voltage. Simulation studies were conducted in MATLAB/Simulink, where two typical operating conditions, including the variation of load power and bus voltage, were designed to verify the effectiveness of the proposed method. Moreover, a traditional PID controller was used as a comparison to reflect the superiority of the former. Simulation results showed that the proposed method is able to guarantee large-signal stability of the system in the presence of large-scale variations in load power and bus voltage. The output current of the parallel converters can also be distributed in desired proportions according to the droop coefficient.
Effects of International Crude Oil Prices on Energy Consumption in China
Authors: Zou Gaolu , Chau Kwong Wing
Published: July 2020

This study aims to test the effects of changes in international crude oil prices on changes in crude oil and hydropower use from 1965 to 2016. We suggest a cointegration relationship between the consumption of coal, crude oil, and hydropower and the real crude oil price. The real price is weakly exogenous for the long-run relationship and has impacted energy consumption accordingly. The long-run crude oil price elasticity of oil use is 0.460. Our estimate suggests a positive oil price–oil use relationship in China, which is dramatically different from many previous studies but is consistent with a few past studies. The growth in external oil prices may lead to a long-run increase in hydropower use in China, with a long-run price elasticity of 0.242. The long-run crude oil price elasticity of coal use is −0.930. Hence, increased oil and hydropower use could make up the energy supply–demand gap left over by the decreased coal use. Strictly planned domestic fuel prices and rapidly growing family incomes should diminish the negative effect of external oil prices on domestic crude oil demand. In the long run, given a strictly managed energy price, the growth in external oil prices is not likely to noticeably restrain the domestic oil demand or lead to a dramatic increase in coal use. We suggest that the large-scale development and utilization of hydropower may be inappropriate. Coal utilization policies must be reviewed. The appropriate increase in clean coal consumption could reduce the consumption of crude oil and hydropower; meanwhile, carbon emissions will not increase.
Operation Characteristics for the Superconducting Arc-Induction Type DC Circuit Breaker
Authors: Park Sangyong , Choi Hyosang
Published: July 2020

The multi-terminal direct current network is expected to commercialize while carrying out projects related to DC power systems worldwide. Accordingly, it is necessary to develop a DC circuit breaker required for the DC power system. A DC circuit breaker should be developed to protect the DC power system and the consumer from the transient state on the line in any case. Currently, the use of power semiconductors increases the performance of DC circuit breakers. However, power semiconductors are expensive and suffer series of losses from frequent failures. Therefore, the DC circuit breaker must have a reliable, stable, and inexpensive structure. We proposed a new type of arc-induction type DC circuit breaker. It consists of a mechanical blocking contact, an induction needle and a superconducting magnet. It blows the arc with an induction needle using the Lorentz force according to the high magnetic field of the superconducting magnet. The arc-induction needle absorbs the arc and flows through the ground wire to the ground to extinguish the arc. We established this principle of arc induction as a mathematical model. In addition, the Maxwell program was used to secure data of electric and magnetic fields and apply them to mathematical models. The results obtained through numerical analysis were analyzed and compared. As a result, we confirmed that the magnitude of the force exerted on the electrons between the mechanical contacts with the superconducting magnets increased about 1.41 times and reasoned the arc-induction phenomenon out numerically.
Modelling Grid Constraints in a Multi-Energy Municipal Energy System Using Cumulative Exergy Consumption Minimisation
Authors: Kriechbaum Lukas , Gradl Philipp , Reichenhauser Romeo , Kienberger Thomas
Published: July 2020

Efficiency measures and the integration of renewable energy sources are key to achieving a sustainable society. The cumulative exergy consumption describes the resource consumption of a product from the raw material to the final utilisation. It includes the exergy expenses for energy infrastructure as well as the imported energy. Since consumers and renewable potentials are usually in different locations, grid restrictions and energy flows have a significant impact on the optimal energy system design. In this paper we will use cumulative exergy minimisation together with load flow calculations to determine the optimal system design of a multi-cell municipal energy system. Two different load flow representations are compared. The network flow model uses transmission efficiencies for heat, gas and electricity flows. The power flow representation uses a linear DC approximated load flow for electricity flows and a MILP (mixed integer linear programming) representation for heat and gas flows to account for the nonlinear pressure loss relation. Although both representations provide comparable overall results, the installed capacities in the individual cells differ significantly. The differences are greatest in well meshed cells, while they are small in stub lines.
Kinematics and Timing Constraints in a Transpressive Tectonic Regime: The Example of the Posada-Asinara Shear Zone (NE Sardinia, Italy)
Authors: Carosi Rodolfo , Petroccia Alessandro , Iaccarino Salvatore , Simonetti Matteo , Langone Antonio , Montomoli Chiara
Published: July 2020

Detailed geological field mapping, integrated with meso- and microstructural investigations, kinematic of the flow and finite strain analyses, combined with geochronology, are fundamental tools to obtain information on the temperature–deformation–timing path of crystalline rocks and shear zone. The Posada-Asinara shear zone (PASZ) in northern Sardinia (Italy) is a steeply dipping km-thick transpressive shear zone. In the study area, located in the Baronie region (NE Sardinia), the presence of mylonites within the PASZ, affecting high- and medium-grade metamorphic rocks, provides an opportunity to quantify finite strain and kinematic vorticity. The main structures of the study area are controlled by a D2 deformation phase, linked to the PASZ activity, in which the strain is partitioned into folds and shear zone domains. Applying two independent vorticity methods, we detected an important variation in the percentage of pure shear and simple shear along the deformation gradient, that increases from south to north. We constrained, for the first time in this sector, the timing of the transpressive deformation by U–(Th)–Pb analysis on monazite. Results indicate that the shear zone has been active at ~325–300 Ma in a transpressive setting, in agreement with the ages of the other dextral transpressive shear zones in the southern Variscan belt.
Physical Activity-Dependent Regulation of Parathyroid Hormone and Calcium-Phosphorous Metabolism
Authors: Lombardi Giovanni , Ziemann Ewa , Banfi Giuseppe , Corbetta Sabrina
Published: July 2020

Exercise perturbs homeostasis, alters the levels of circulating mediators and hormones, and increases the demand by skeletal muscles and other vital organs for energy substrates. Exercise also affects bone and mineral metabolism, particularly calcium and phosphate, both of which are essential for muscle contraction, neuromuscular signaling, biosynthesis of adenosine triphosphate (ATP), and other energy substrates. Parathyroid hormone (PTH) is involved in the regulation of calcium and phosphate homeostasis. Understanding the effects of exercise on PTH secretion is fundamental for appreciating how the body adapts to exercise. Altered PTH metabolism underlies hyperparathyroidism and hypoparathyroidism, the complications of which affect the organs involved in calcium and phosphorous metabolism (bone and kidney) and other body systems as well. Exercise affects PTH expression and secretion by altering the circulating levels of calcium and phosphate. In turn, PTH responds directly to exercise and exercise-induced myokines. Here, we review the main concepts of the regulation of PTH expression and secretion under physiological conditions, in acute and chronic exercise, and in relation to PTH-related disorders.
Application of Antibodies to Neuronally Expressed Nogo-A Increases Neuronal Survival and Neurite Outgrowth
Authors: Nagaraj Vini , Theis Thomas , Johal Anmol Singh , Seth Arihant , Gore Jada , Arsha Neha , Patel Mukti , Hao Helen Baixia , Kurian Nikki , Schachner Melitta
Published: July 2020

Nogo-A, a glycoprotein expressed in oligodendrocytes and central nervous system myelin, inhibits regeneration after injury. Antibodies against Nogo-A neutralize this inhibitory activity, improve locomotor recovery in spinal cord-injured adult mammals, and promote regrowth/sprouting/saving of damaged axons beyond the lesion site. Nogo-A is also expressed by neurons. Complete ablation of Nogo-A in all cell types expressing it has been found to lead to recovery in some studies but not in others. Neuronal ablation of Nogo-A reduces axonal regrowth after injury. In view of these findings, we hypothesized that, in addition to neutralizing Nogo-A in oligodendrocytes and myelin, Nogo-A antibodies may act directly on neuronal Nogo-A to trigger neurite outgrowth and neuronal survival. Here, we show that polyclonal and monoclonal antibodies against Nogo-A enhance neurite growth and survival of cultured cerebellar granule neurons and increase expression of the neurite outgrowth-promoting L1 cell adhesion molecule and polysialic acid. Application of inhibitors of signal transducing molecules, such as c-src, c-fyn, protein kinase A, and casein kinase II reduce antibody-triggered neurite outgrowth. These observations indicate that the recovery-promoting functions of antibodies against Nogo-A may not only be due to neutralizing Nogo-A in oligodendrocytes and myelin, but also to their interactions with Nogo-A on neurons.
Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed βH-Crystallins Polymerization in Calcium-Induced Experimental Cataract
Authors: Mischiati Carlo , Feriotto Giordana , Tabolacci Claudio , Domenici Fabio , Melino Sonia , Borromeo Ilaria , Forni Cinzia , De Martino Angelo , Beninati Simone
Published: July 2020

In an in vitro Ca2+-induced cataract model, the progression of opacification is paralleled by a rapid decrease of the endogenous levels of spermidine (SPD) and an increase of transglutaminase type 2 (TG2, EC 2.3.2.13)-catalyzed lens crystallins cross-linking by protein-bound N1-N8-bis(γ-glutamyl) SPD. This pattern was reversed adding exogenous SPD to the incubation resulting in a delayed loss of transparency of the rabbit lens. The present report shows evidence on the main incorporation of SPD by the catalytic activity of TG2, toward βH-crystallins and in particular to the βB2- and mostly in βB3-crystallins. The increase of endogenous SPD in the cultured rabbit lens showed the activation of a flavin adenine dinucleotide (FAD)-dependent polyamine oxidases (PAO EC 1.5.3.11). As it is known that FAD-PAO degrades the N8-terminal reactive portion of N1-mono(γ-glutamyl) SPD, the protein-bound N8-mono(γ-glutamyl) SPD was found the mainly available derivative for the potential formation of βB3-crystallins cross-links by protein-bound N1-N8-bis(γ-glutamyl)SPD. In conclusion, FAD-PAO degradation of the N8-terminal reactive residue of the crystallins bound N1-mono(γ-glutamyl)SPD together with the increased concentration of exogenous SPD, leading to saturation of glutamine residues on the substrate proteins, drastically reduces N1-N8-bis(γ-glutamyl)SPD crosslinks formation, preventing crystallins polymerization and avoiding rabbit lens opacification. The ability of SPD and MDL 72527 to modulate the activities of TG2 and FAD-PAO involved in the mechanism of lens opacification suggests a potential strategy for the prevention of senile cataract.
Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma
Authors: Burgio Stefano , Noori Leila , Marino Gammazza Antonella , Campanella Claudia , Logozzi Mariantonia , Fais Stefano , Bucchieri Fabio , Cappello Francesco , Caruso Bavisotto Celeste
Published: July 2020

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.
Innate Immune Response to Tick-Borne Pathogens: Cellular and Molecular Mechanisms Induced in the Hosts
Authors: Torina Alessandra , Villari Sara , Blanda Valeria , Vullo Stefano , La Manna Marco Pio , Shekarkar Azgomi Mojtaba , Di Liberto Diana , de la Fuente José , Sireci Guido
Published: July 2020

Many pathogens are transmitted by tick bites, including Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species. These pathogens cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen-derived antigens or indirectly by molecules released by host cells binding to these antigens. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. During the infection caused by different microbial agents, very similar profiles of the human innate immune response are observed including secretion of IL-1α, IL-8, and IFN-α, and suppression of superoxide dismutase, IL-1Ra and IL-17A release. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The ongoing research field of “inflammasome biology” focuses on the interactions among molecules and cells of innate immune response that could be responsible for triggering a protective adaptive immunity. The knowledge of the innate immunity mechanisms, as well as the new targets of investigation arising by bioinformatics analysis, could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections.
Proteomics and Metabolomics for Cystic Fibrosis Research
Authors: Liessi Nara , Pedemonte Nicoletta , Armirotti Andrea , Braccia Clarissa
Published: July 2020

The aim of this review article is to introduce the reader to the state-of-the-art of the contribution that proteomics and metabolomics sciences are currently providing for cystic fibrosis (CF) research: from the understanding of cystic fibrosis transmembrane conductance regulator (CFTR) biology to biomarker discovery for CF diagnosis. Our work particularly focuses on CFTR post-translational modifications and their role in cellular trafficking as well as on studies that allowed the identification of CFTR molecular interactors. We also show how metabolomics is currently helping biomarker discovery in CF. The most recent advances in these fields are covered by this review, as well as some considerations on possible future scenarios for new applications.
Magnetic Stimulation Drives Macrophage Polarization in Cell to–Cell Communication with IL-1β Primed Tendon Cells
Authors: Vinhas Adriana , Almeida Ana F. , Gonçalves Ana I. , Rodrigues Márcia T. , Gomes Manuela E.
Published: July 2020

Inflammation is part of the natural healing response, but it has been simultaneously associated with tendon disorders, as persistent inflammatory events contribute to physiological changes that compromise tendon functions. The cellular interactions within a niche are extremely important for healing. While human tendon cells (hTDCs) are responsible for the maintenance of tendon matrix and turnover, macrophages regulate healing switching their functional phenotype to environmental stimuli. Thus, insights on the hTDCs and macrophages interactions can provide fundamental contributions on tendon repair mechanisms and on the inflammatory inputs in tendon disorders. We explored the crosstalk between macrophages and hTDCs using co-culture approaches in which hTDCs were previously stimulated with IL-1β. The potential modulatory effect of the pulsed electromagnetic field (PEMF) in macrophage-hTDCs communication was also investigated using the magnetic parameters identified in a previous work. The PEMF influences a macrophage pro-regenerative phenotype and favors the synthesis of anti-inflammatory mediators. These outcomes observed in cell contact co-cultures may be mediated by FAK signaling. The impact of the PEMF overcomes the effect of IL-1β-treated-hTDCs, supporting PEMF immunomodulatory actions on macrophages. This work highlights the relevance of intercellular communication in tendon healing and the beneficial role of the PEMF in guiding inflammatory responses toward regenerative strategies.
Proteinaceous Transformers: Structural and Functional Variability of Human sHsps
Authors: Riedl Mareike , Strauch Annika , Catici Dragana A.M. , Haslbeck Martin
Published: July 2020

The proteostasis network allows organisms to support and regulate the life cycle of proteins. Especially regarding stress, molecular chaperones represent the main players within this network. Small heat shock proteins (sHsps) are a diverse family of ATP-independent molecular chaperones acting as the first line of defense in many stress situations. Thereby, the promiscuous interaction of sHsps with substrate proteins results in complexes from which the substrates can be refolded by ATP-dependent chaperones. Particularly in vertebrates, sHsps are linked to a broad variety of diseases and are needed to maintain the refractive index of the eye lens. A striking key characteristic of sHsps is their existence in ensembles of oligomers with varying numbers of subunits. The respective dynamics of these molecules allow the exchange of subunits and the formation of hetero-oligomers. Additionally, these dynamics are closely linked to the chaperone activity of sHsps. In current models a shift in the equilibrium of the sHsp ensemble allows regulation of the chaperone activity, whereby smaller oligomers are commonly the more active species. Different triggers reversibly change the oligomer equilibrium and regulate the activity of sHsps. However, a finite availability of high-resolution structures of sHsps still limits a detailed mechanistic understanding of their dynamics and the correlating recognition of substrate proteins. Here we summarize recent advances in understanding the structural and functional relationships of human sHsps with a focus on the eye-lens αA- and αB-crystallins.
In Experimental Dilated Cardiomyopathy Heart Failure and Survival Are Adversely Affected by a Lack of Sexual Interactions
Authors: Tripathi Ranjana , Sullivan Ryan D. , Fan Tai-Hwang M. , Mehta Radhika M. , Gladysheva Inna P. , Reed Guy L.
Published: July 2020

Nearly one in three people in the U.S. will develop heart failure (HF), characterized by fluid retention (edema) in the lungs and elsewhere. This leads to difficult breathing, deterioration of physical capacity, restriction of normal activities and death. There is little data about the safety and effects of sexual interactions in patients with HF. We tested whether a lack of sexual interactions affected pathophysiological outcomes in a pre-clinical mouse model of dilated cardiomyopathy that recapitulates the progressive stages of human HF. Male mice were randomly given access to, or deprived from, sexual interactions with female mice, which were confirmed by videography and generation of offspring. Cohousing with access to sexual interactions markedly prolonged survival, while cohousing without access to sexual activity did not. Sexual interactions improved systolic function, reduced HF-associated edema, altered transcription of heart contractile protein genes and decreased plasma testosterone levels. To determine whether testosterone levels contributed to survival, testosterone levels were experimentally reduced. Reduction of testosterone levels significantly prolonged survival. Taken together, in mice with dilated cardiomyopathy, sexual activity altered cardiac contractile gene transcription, improved systolic function, reduced edema and prolonged survival which may be in part due to lower testosterone levels.
Osteosarcoma-Derived Extracellular Vesicles Induce Lung Fibroblast Reprogramming
Authors: Mazumdar Alekhya , Urdinez Joaquin , Boro Aleksandar , Migliavacca Jessica , Arlt Matthias J.E. , Muff Roman , Fuchs Bruno , Snedeker Jess Gerrit , Gvozdenovic Ana
Published: July 2020

Tumor-secreted extracellular vesicles (EVs) have been identified as mediators of cancer–host intercellular communication and shown to support pre-metastatic niche formation by modulating stromal cells at future metastatic sites. While osteosarcoma, the most common primary malignant bone tumor in children and adolescents, has a high propensity for pulmonary metastases, the interaction of osteosarcoma cells with resident lung cells remains poorly understood. Here, we deliver foundational in vitro evidence that osteosarcoma cell-derived EVs drive myofibroblast/cancer-associated fibroblast differentiation. Human lung fibroblasts displayed increased invasive competence, in addition to increased α-smooth muscle actin expression and fibronectin production upon EV treatment. Furthermore, we demonstrate, through the use of transforming growth factor beta receptor 1 (TGFBR1) inhibitors and CRISPR-Cas9-mediated knockouts, that TGFβ1 present in osteosarcoma cell-derived EVs is responsible for lung fibroblast differentiation. Overall, our study highlights osteosarcoma-derived EVs as novel regulators of lung fibroblast activation and provides mechanistic insight into how osteosarcoma cells can modulate distant cells to potentially support metastatic progression.
VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines
Authors: El Dor Maya , Dakik Hassan , Polomski Marion , Haudebourg Eloi , Brachet Marie , Gouilleux Fabrice , Prié Gildas , Zibara Kazem , Mazurier Frédéric
Published: July 2020

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) involvement has been established in the oncogenic cell signaling of acute myeloid leukemia (AML) cells and in the crosstalk with their niche. We have shown an expression of NOX subunits in AML cell lines while NOX activity is lacking in the absence of exogenous stimulation. Here, we used AML cell lines as models to investigate the specificity of VAS3947, a current NOX inhibitor. Results demonstrated that VAS3947 induces apoptosis in AML cells independently of its anti-NOX activity. High-performance liquid chromatography (HPLC) and mass spectrometry analyses revealed that VAS3947 thiol alkylates cysteine residues of glutathione (GSH), while also interacting with proteins. Remarkably, VAS3947 decreased detectable GSH in the MV-4-11 cell line, thereby suggesting possible oxidative stress induction. However, a decrease in both cytoplasmic and mitochondrial reactive oxygen species (ROS) levels was observed by flow cytometry without disturbance of mitochondrial mass and membrane potential. Thus, assuming the consequences of VAS3947 treatment on protein structure, we examined its impact on endoplasmic reticulum (ER) stress. An acute unfolded protein response (UPR) was triggered shortly after VAS3947 exposure, through the activation of inositol-requiring enzyme 1α (IRE1α) and PKR-like endoplasmic reticulum kinase (PERK) pathways. Overall, VAS3947 induces apoptosis independently of anti-NOX activity, via UPR activation, mainly due to aggregation and misfolding of proteins.
A Piecewise-Defined Function for Modelling Traffic Noise on Urban Roads
Authors: Gallo Mariano
Published: July 2020

In this paper, a piecewise-defined function is proposed to estimate traffic noise in urban areas. The proposed approach allows the use of the model even in the case of very low or zero flows for which the classical logarithmic form is not suitable. A model based on the proposed approach is calibrated for a real case and compared with the results obtained with a model based only on the logarithmic form. The results obtained show how the proposed piecewise-defined function, linear for low traffic flows and logarithmic for medium-high volumes, is able to better represent real noise pollution levels in all conditions. The proposed approach is particularly useful when comparing two plan scenarios from the point of view of noise effects.
Thermal Effects on the Population Parameters and Growth of Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae)
Authors: Ahn Jeong Joon , Cho Jum Rae , Kim Jeong-Hwan , Seo Bo Yoon
Published: July 2020

The pea aphid Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae) is a cosmopolitan and polyphagous species. An evaluation of A. pisum’s demographic parameters and growth was carried out after rearing aphids on faba bean plants (Vicia faba) under five different temperature conditions (10 °C, 15 °C, 20 °C, 25 °C and 30 °C). We analyzed the raw life history data, including developmental time, survival, longevity and reproduction, using an age-stage, two-sex life table to consider variable developmental rates among individuals. The population fluctuation of A. pisum determined the stage-specific population structure and potential population growth under different temperature conditions. A. pisum individuals developed successfully from nymphs to adults at all temperatures in this study. The developmental rate of A. pisum increased as the temperature increased. Our results indicated that A. pisum showed a higher pre-adult mortality, lower total fecundity and a negative intrinsic rate of increase at 30 °C. The highest intrinsic rate of increase (0.30) and finite rate of increase (1.35) were observed at 25 °C. Comparisons of population parameters and their analytical methods between different A. pisum populations from other geographic areas are also discussed.
An Alternative, High Throughput Method to Identify Csd Alleles of the Honey Bee
Authors: Kolics Éva , Parrag Tamás , Házi Ferenc , Szepesi Kinga , Heltai Botond , Mátyás Kinga , Kutasy Barbara , Virág Eszter , Taller János , Orbán László , Kolics Balázs
Published: July 2020

Applying instrumental insemination in closely related honey bee colonies often leads to frequent lethality of offspring causing colony collapse. This is due to the peculiarities of honey bee reproductive biology, where the complementary sex determination (csd) gene drives sex determination within a haplodiploid system. Diploid drones containing homozygous genotypes are lethal. Tracking of csd alleles using molecular markers prevents this unwanted event in closed breeding programs. Our approach described here is based on high throughput sequencing (HTS) that provides more data than traditional molecular techniques and is capable of analysing sources containing multiple alleles, including diploid individuals as the bee queen. The approach combines HTS technique and clipping wings as a minimally invasive method to detect the complementary sex determiner (csd) alleles directly from honey bee queens. Furthermore, it might also be suitable for screening alleles of honey harvested from hives of a closed breeding facility. Data on alleles of the csd gene from different honey bee subspecies are provided. It might contribute to future databases that could potentially be used to track the origin of honey. With the help of tracking csd alleles, more focused crossings will be possible, which could in turn accelerate honey bee breeding programmes targeting increase tolerance against varroosis as well.