bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards antagonistic cosmopolitanism. A theoretical attempt to work though the controversy about the shape of global democracy
Authors: Minkner Kamil
Published: October 2021

The article presents the analysis of the relation between two concepts, namely cosmopolitan democracy and agonistic multipolar order, whose author is Chantal Mouffe, in the context of the dispute about the preferred shape of global democracy. Both approaches are presented in the literature as opposing. The main thesis of the present article is the possibility of connecting them, but according to dialectical principles. The point is not about a smooth consensus but about the fact that the contradictions between those views can be treated as a condition of their interweaving. To this aim, I use two theoretical concepts: of antagonistic cosmopolitanism by Tamara Caraus and of antagonistic global constitutionalism by Christof Royer. On this basis I claim that Mouffe’s rejection of cosmopolitanism is not thoroughly coherent with her own assumptions. I acknowledge her argumentation that cosmopolitan democracy might lead to pluralism without antagonism but at the same time I suggest that Mouffe’s postulate of the multipolar order can lead to pluralist antagonism without agonism. It is only the establishment of cosmopolitan institutions and rules that will allow for really agonistic and radically pluralized global politics, thanks to which it will be possible to solve the contemporary world problems effectively. For these reasons agonistic cosmopolitanism can be regarded as the most optimal variant of global democracy.
ANAHIT MANASYAN Constitutional stability as an important prerequisite for stable democracy
Authors: Kyliushyk Ivanna
Published: October 2021

The author of the book examines the issues of constitutional stability and its role in ensuring sustainable democracy.
The world public opinion towards the American foreign policy of presidents of the United States of North America in the years 2001–2016
Authors: Potocki Przemysław
Published: October 2021

The article is based on an analysis of certain aspects of how the public opinion of selected nations in years 2001–2016 perceived the American foreign policy and the images of two Presidents of the United States (George W. Bush, Barack Obama). In order to achieve these research goals some polling indicators were constructed. They are linked with empirical assessments related to the foreign policy of the U.S. and the political activity of two Presidents of the United States of America which are constructed by nations in three segments of the world system. Results of the analysis confirmed the research hypotheses. The position of a given nation in the structure of the world system influenced the dynamics of perception and the directions of empirical assessments (positive/negative) of that nation’s public opinion about the USA.
Comparative Study of Different Algorithms for a Flight Control System Design and the Potentiality of Their Integration with a Sidestick
Authors: Efremov Alexandr V. , Mbikayi Zoe , Efremov Eugene V.
Published: October 2021

The modern trend of developing highly automated aircraft is characterized by a transition from traditional methods and technical solutions to innovative approaches in order to control the system, inceptor and display design. This paper deals with the development and comparison of flight control system algorithms based on inverse dynamics, H-infinity and traditional feedback methods. The integration of a controller based on inverse dynamics with a novel type of sidestick, shaping the pilot output signal such that it is proportional to the control force (force sensing control—FSC), is studied. The inverse dynamics-based controller is chosen, as it provides a variance of error that is up to 2.3 times less than that of the feedback gains and up to 1.5 times less than that of the H-infinity controller in a pitch tracking task. The synergetic effect arising from the proposed integration is also evaluated. The evaluation of the effectiveness of the methods is carried out through mathematical modeling of the pilot–aircraft system and ground-based simulations on a helicopter mathematical model in a pitch tracking task.
Smart Indoor Farms: Leveraging Technological Advancements to Power a Sustainable Agricultural Revolution
Authors: Hati Anirban Jyoti , Singh Rajiv Ranjan
Published: October 2021

Conventional farming necessitates a large number of resources and infrastructure such as land, irrigation, manpower to manage farms, etc. Modern initiatives are required to automate conventional farms. Smart indoor farms offer the potential to remedy the shortfalls of conventional farms by providing a controlled, intelligent, and smart environment. This paper presents a three-dimensional perspective consisting of soilless farming, energy harvesting, and smart technologies, which could be considered as the three important characteristics of smart indoor farms. A six-layer smart indoor farms architecture has also been proposed, which explains how data are collected using various sensors and devices and then transmitted onto the cloud infrastructure for further analysis and control through various layers. Artificial lighting, smart nutrition management, and artificial climate control, to name a few, are some of the important requirements for smart indoor farms while considering control and service management factors. The major bottleneck in installing such systems is both the economical and the technical constraints. However, with the evolution of technology (and when they become widely available in the near future), a more favourable farming scenario may emerge. Furthermore, smart indoor farms could be viewed as a potential answer for meeting the demands of a sustainable agricultural revolution as we move closer to Agriculture 4.0. Finally, in order to adapt smart indoor farms and their study scope, our work has presented various research areas to potential researchers.
Crop Response to Combined Availability of Soil Water and Its Salinity Level: Theory, Experiments and Validation on Golf Courses
Authors: Ben-Asher Jiftah , Beltrao Jose , Bekmirzaev Gulom , Panagopoulos Thomas
Published: October 2021

The phenomenological expression showing crop yield to be directly dependent on water deficiency, under saline conditions, has encouraged a continued focus on salinity as a viable approach to increase crop yields. This work reassesses crop response to availability of saline soil water ASW in two stages (A) Develop a simple approach suggesting that permanent wilting point (WP) increases under high saline soil water tension and relative yield of Lettuce (Lactuca sativa L., var longifolia Lam., cv. Nevada) and maize (Zea mays L., cv. Jubilee sweet) decrease. (B) Using a deterministic numerical soil water model to validate the theory on Bermuda grass of golf courses. The experimental plots were established in the North Negev, Israel (Sweet corn) and the Algarve, Portugal (Lettuce and Bermuda grass covering the golf courses). Sprinkler irrigation and line source techniques were used for water application, creating a saline gradient under a precise irrigation water distribution. Two salinity empirical models were tested (Mass and Hoffman MH and van Genuchten–Gupta vGG). Their empirical models were modified and instead of soil electrical conductivity of irrigation water (ECe) we used wilting point (WP) and RASW to follow the changes in relative yield. The validation was conducted with theoretical soil plant atmosphere water (SPAW) to predict the results on golf courses. It is concluded that an alternative S-shaped response model provides better fit to our experimental data sets. Modified MH model (Yr = Y/Ymax = a ∗ (ASW–threshold’s constant) revealed that a single dimensionless curve could be used to express yield—salinity interference when represented by varying ASW. The vGG model: vGG can represent salt tolerance of most crops, by using varying wilting point of average root zone salinity, at which the yield has declined by 50%. The abscissa of both models was based on WP rather than the standard soil electrical conductivity (ECw). The correlation between the experimental data and WP or relative available soil water (RASW) was acceptable and, therefore, their usefulness for prediction of relative yield is acceptable as well. The objectives of this study were: 1. To develop a simple model describing the effect of salinity through soil water availability on crop production; 2. To replace the standard varying soil electrical conductivity ECe used by MH and vGG models by two soil parameters (at wilting point- θwp and at field capacity θfc) in order to describe the relationship between them and relative yield. 3. Validate the new model with respect to independent salinity on Golf courses and a mathematical deterministic model.
Effect of Dynamic Bridging on Homogeneous Grain Movement in a Microwave Processing Zone
Authors: Vasilyev Alexey A. , Vasilyev Alexey N. , Budnikov Dmitry , Bolshev Vadim , Jasinski Michal , Leonowicz Zbigniew , Gono Radomir , Jasinski Lukasz
Published: October 2021

This article describes the influence of dynamic bridging in the unloading of a hopper at a processing plant on the grain flow homogeneity in a convective-microwave zone. In accordance with calculation methods for unloading hoppers, the parameters of the hopper unit and those of the outlet hole insuring that grain flows without static bridging formation is defined. It was found that moisture content fluctuations do not affect the process of grain transport. The equation for dynamic bridging rise depending on its position on the vertical axis of the unloading hopper has been deduced that enables the definition of the inhomogeneity of grain flow from its outlet hole. Calculations show that a certain inhomogeneity occurred between the right and the left parts of the unloading hopper in relation to its vertical axis in the course of grain discharging. This effect underlies the inhomogeneity of grain processing and reduction of its effectiveness in convective-microwave zones. An experimental model of unloading the hopper has been manufactured in order to perform investigational studies. The results of studies have completely confirmed the hypotheses. It has been found that dynamic bridge formation in unloading of the hopper results in the inhomogeneity of grain flow in convective-microwave zone.
Activity of Two Antimicrobial Peptides against Enterococcus faecalis in a Model of Biofilm-Mediated Endodontic Infection
Authors: Mergoni Giovanni , Manfredi Maddalena , Bertani Pio , Ciociola Tecla , Conti Stefania , Giovati Laura
Published: October 2021

Enterococcus faecalis is a common cause of biofilm-associated opportunistic infections, which are often difficult to treat. The formation of E. faecalis biofilms on the dentinal walls of the root canal is frequently the cause of endodontic treatment failure and secondary apical periodontitis. In a preliminary work, two recognized antifungal peptides, KP and L18R, showed antibacterial activity against planktonic E. faecalis cells at micromolar concentrations. Moreover, L18R proved to reduce the biomass in the early stage of E. faecalis biofilm development on polystyrene plates, while a qualitative biofilm inhibition was demonstrated on hydroxyapatite disks by confocal laser scanning microscopy (CLSM). The aim of this study was to better characterize the effect of both peptides on E. faecalis biofilm. A reduction in metabolic activity after peptide treatment was detected by Alamar Blue assay, while a remarkable impairment in the architecture of E. faecalis biofilms on hydroxyapatite disks, along with a significant reduction in viable bacteria, was caused mostly by L18R, as assessed by CLSM and scanning electron microscopy. The lack of cytotoxicity of the investigated peptides against L929 murine fibroblasts was also determined. Obtained results suggest L18R as a promising candidate for the development of new strategies for endodontic infection control.
Comparative In Vitro Antioxidant Capacity and Terpenoid Profiling of Pumpkin Fruit Pulps from a Serbian Cucurbita maxima and Cucurbita moschata Breeding Collection
Authors: Miljić Milorad , Rocchetti Gabriele , Krstić Sanja , Mišan Aleksandra , Brdar-Jokanović Milka , Marcheggiani Fabio , Martinelli Erika , Lucini Luigi , Damiani Elisabetta
Published: October 2021

Pumpkin is considered a healthy and functional food. The consumption of pumpkins and pumpkin-based foods has been shown to confer several beneficial effects on human health due to their antioxidant capacity and terpenoid content. Consequently, this study aimed to characterize the in vitro antioxidant capacity (using FRAP and ABTS assays), terpenoid profile (using an untargeted lipidomics approach via high-resolution UHPLC-Orbitrap mass spectrometry), and carotenoid content (by HPLC-DAD) in pumpkin fruit pulp from accessions differing for species (11 Cucurbita maxima and 9 Cucurbita moschata), cultivar, and origin, belonging to a Serbian breeding collection. These accessions are candidates for inclusion within programs intended to improve pumpkin fruit quality. The results obtained in this work allowed us to highlight the best marker compounds, discriminating both the region of accession collection or breeding (“origin”) and the plant species. Furthermore, our findings have helped to identify the most suitable antioxidant-rich varieties to select for national breeding programs for improving human health. These findings provide valuable information to the overall current understanding of the potential health benefits of pumpkins and the discriminant triterpenoids underlying the C. maxima and C. moschata accessions investigated here, which include those of Serbian and non-Serbian origin.
Power Sharing Control in a Grid-Tied DC Microgrid: Controller Hardware in the Loop Validation
Authors: Samano-Ortega Víctor , Rodriguez-Estrada Heriberto , Rodríguez-Segura Elías , Padilla-Medina José , Aguilera-Alvarez Juan , Martinez-Nolasco Juan
Published: October 2021

This article presents the development of a low-cost control hardware in the loop platform for the validation and analysis of controllers used for the management of power sharing between the main grid and a DC microgrid. The platform is made up of two parts: a main grid interconnection system emulator (MGISE) and a controller under test (CUT). The MGISE operates on a 260 V DC bus and includes a 1000 W photovoltaic array, a DC variable load and a single H full bridge converter (HFBC). The CUT includes a phase locked loop and a main cascade control structure composed of two PI controllers. Both the MGISE and the CUT were embedded on an NI myRIO-1900 development board and programmed using LabVIEW virtual instrumentation software. These devices communicate with each other using analog signals representing the AC side current, the DC side voltage, and the HFBC control signal. The MGISE operates with an integration time of 6 µs and its performance is validated by comparing it with a simulation in PSIM. The integration time of the MGISE, the development boards used, as well as its programming environment, and the results obtained from the comparison with PSIM simulation, show that the proposed platform is useful for the validation of controllers for power sharing, with a simple implementation process compared to other hardware description methods and with a low-cost platform.
Health Care Resource Use at End of Life in Patients with Advanced Lung Cancer
Authors: Oselin Kersti , Pisarev Heti , Ilau Keit , Kiivet Raul-Allan
Published: October 2021

We aimed to study differences in the use of health care resources in relation to time before death in patients with advanced lung cancer who either received systemic anti-cancer treatment (SACT) or were ineligible for SACT. A retrospective cohort of lung cancer patients (N = 778) diagnosed with advanced disease at North Estonia Medical Centre from 2015–2017 was linked to population-based health care data. We calculated a composite measure of cumulative resource use, comprised from the following: outpatient care, emergency department (ED) visit, inpatient care, admission to intensive care unit, nursing care and prescriptions. Costs were highest in patients who received SACT in the last month before death and decreased in parallel with the time elapsed from the last SACT. Only 20% of SACT patients received nursing care in the final month of life. The no-SACT patients had less time covered by health care services per month, and large differences were seen in the type of service received by the study groups. The largest contributor of health care costs at end of life was acute inpatient care, including approximately 10% of patients who died on the same day as or day following the emergency department visit. These results demonstrate the low nursing care and hospice utilization rates in Estonia.
Method of Source Identification Following an Accidental Release at an Unknown Location Using a Lagrangian Atmospheric Dispersion Model
Authors: Andronopoulos Spyros , Kovalets Ivan V.
Published: October 2021

A computationally efficient source inversion algorithm was developed and applied with the Lagrangian atmospheric dispersion model DIPCOT. In the process of source location estimation by minimizing a correlation-based cost function, the algorithm uses only the values of the time-integrated concentrations at the monitoring stations instead of all of the individual measurements in the full concentration-time series, resulting in a significant reduction in the number of integrations of the backward transport equations. Following the source location estimation the release start time, duration and emission rate are assessed. The developed algorithm was verified for the conditions of the ETEX-I (European Tracer Experiment—1st release). Using time-integrated measurements from all available stations, the distance between the estimated and true source location was 108 km. The estimated start time of the release was only about 1 h different from the true value, within the possible accuracy of estimate of this parameter. The estimated release duration was 21 h (the true value was 12 h). The estimated release rate was 4.28 g/s (the true value was 7.95 g/s). The estimated released mass almost perfectly fitted the true released mass (323.6 vs. 343.4 kg). It thus could be concluded that the developed algorithm is suitable for further integration in real-time decision support systems.
Potentially Toxic Elements (PTEs) Composition and Human Health Risk Assessment of PM10 on the Roadways of Industrial Complexes in South Korea
Authors: Choi Jin-Young , Jeong Hyeryeong , Ra Kongtae , Kim Kyung-Tae
Published: October 2021

Road and industrial origin particulate matters (PM) are a significant source of potentially toxic elements (PTEs), with health risks to the surrounding residents. In Korea for 60 years, although industries, roads and automobiles have increased aggressively, there are still few PTEs data in PM in road-deposited sediment (RDS) of industrial complexes (ICs). Therefore, this study aimed to investigate the PTE composition of on-road PM10 from nine major ICs and its pollution degree in Korea and evaluate its human health risks. The geo-accumulation index (Igeo) and pollution load index (PLI) elucidated that on-road PM10 were severely polluted by Sb, Zn, Ag and Pb. A combination of principal component analysis (PCA) and chemical tracers was used to define the PTEs sources. The results showed that non-exhaust emission from vehicles’ activity is the primary source of PTEs in on-road PM10, and industrial emissions are the secondary source. The riskiest pathway on carcinogenic and non-carcinogenic by on-road PM10 with PTEs was in-gestion. Traffic origin PTEs including Pb, As, Sb and Cd had a more significant impact on carcinogenic and non-carcinogenic health than those of industrial origins. These results could help mitigate public health risks arising from on-road PM10 and improve air quality in ICs.
Forced, Balanced, Axisymmetric Shallow Water Model for Understanding Short-Term Tropical Cyclone Intensity and Wind Structure Changes
Authors: Hendricks Eric A. , Vigh Jonathan L. , Rozoff Christopher M.
Published: October 2021

A minimal modeling system for understanding tropical cyclone intensity and wind structure changes is introduced: Shallow Water Axisymmetric Model for Intensity (SWAMI). The forced, balanced, axisymmetric shallow water equations are reduced to a canonical potential vorticity (PV) production and inversion problem, whereby PV is produced through a mass sink (related to the diabatic heating) and inverted through a PV/absolute–angular–momentum invertibility principle. Because the invertibility principle is nonlinear, a Newton–Krylov method is used to iteratively obtain a numerical solution to the discrete problem. Two versions of the model are described: a physical radius version which neglects radial PV advection (SWAMI-r) and a potential radius version that naturally includes the advection in the quasi-Lagrangian coordinate (SWAMI-R). In idealized numerical simulations, SWAMI-R produces a thinner and more intense PV ring than SWAMI-r, demonstrating the role of axisymmetric radial PV advection in eyewall evolution. SWAMI-R always has lower intensification rates than SWAMI-r because the reduction in PV footprint effect dominates the peak magnitude increase effect. SWAMI-r is next demonstrated as a potentially useful short-term wind structure forecasting tool using the newly added FLIGHT+ Dataset azimuthal means for initialization and forcing on three example cases: a slowly intensifying event, a rapid intensification event, and a secondary wind maximum formation event. Then, SWAMI-r is evaluated using 63 intensifying cases. Even though the model is minimal, it is shown to have some skill in short-term intensity prediction, highlighting the known critical roles of the relationship between the radial structures of the vortex inertial stability and diabatic heating rate. Because of the simplicity of the models, SWAMI simulations are completed in seconds. Therefore, they may be of some use for hurricane nowcasting to short-term (less than 24 h) intensity and structure forecasting. Due to its favorable assumptions for tropical cyclone intensification, a potential use of SWAMI is a reasonable short-term upper-bound intensity forecast if the storm intensifies.
Activation of Aldehyde Dehydrogenase 2 Ameliorates Glucolipotoxicity of Pancreatic Beta Cells
Authors: Chen Shiau-Mei , Hee Siow-Wey , Chou Shih-Yun , Liu Meng-Wei , Chen Che-Hong , Mochly-Rosen Daria , Chang Tien-Jyun , Chuang Lee-Ming
Published: October 2021

Chronic hyperglycemia and hyperlipidemia hamper beta cell function, leading to glucolipotoxicity. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies reactive aldehydes, such as methylglyoxal (MG) and 4-hydroxynonenal (4-HNE), derived from glucose and lipids, respectively. We aimed to investigate whether ALDH2 activators ameliorated beta cell dysfunction and apoptosis induced by glucolipotoxicity, and its potential mechanisms of action. Glucose-stimulated insulin secretion (GSIS) in MIN6 cells and insulin secretion from isolated islets in perifusion experiments were measured. The intracellular ATP concentrations and oxygen consumption rates of MIN6 cells were assessed. Furthermore, the cell viability, apoptosis, and mitochondrial and intracellular reactive oxygen species (ROS) levels were determined. Additionally, the pro-apoptotic, apoptotic, and anti-apoptotic signaling pathways were investigated. We found that Alda-1 enhanced GSIS by improving the mitochondrial function of pancreatic beta cells. Alda-1 rescued MIN6 cells from MG- and 4-HNE-induced beta cell death, apoptosis, mitochondrial dysfunction, and ROS production. However, the above effects of Alda-1 were abolished in Aldh2 knockdown MIN6 cells. In conclusion, we reported that the activator of ALDH2 not only enhanced GSIS, but also ameliorated the glucolipotoxicity of beta cells by reducing both the mitochondrial and intracellular ROS levels, thereby improving mitochondrial function, restoring beta cell function, and protecting beta cells from apoptosis and death.
Coordination of RNA Processing Regulation by Signal Transduction Pathways
Authors: Ruta Veronica , Pagliarini Vittoria , Sette Claudio
Published: October 2021

Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.
Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review
Authors: Alehagen Urban , Opstad Trine B. , Alexander Jan , Larsson Anders , Aaseth Jan
Published: October 2021

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals.
Clumps of Mesenchymal Stem Cells/Extracellular Matrix Complexes Generated with Xeno-Free Chondro-Inductive Medium Induce Bone Regeneration via Endochondral Ossification
Authors: Horikoshi Susumu , Kajiya Mikihito , Motoike Souta , Yoshino Mai , Morimoto Shin , Yoshii Hiroki , Ogawa Tomoya , Sone Hisakatsu , Iwata Tomoyuki , Ouhara Kazuhisa , Matsuda Shinji , Mizuno Noriyoshi , Kurihara Hidemi
Published: October 2021

Three-dimensional clumps of mesenchymal stem cells (MSCs)/extracellular matrix (ECM) complexes (C-MSCs) can be transplanted into tissue defect site with no artificial scaffold. Importantly, most bone formation in the developing process or fracture healing proceeds via endochondral ossification. Accordingly, this present study investigated whether C-MSCs generated with chondro-inductive medium (CIM) can induce successful bone regeneration and assessed its healing process. Human bone marrow-derived MSCs were cultured with xeno-free/serum-free (XF) growth medium. To obtain C-MSCs, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and then torn off. The sheet was rolled to make a round clump of cells. The cell clumps, i.e., C-MSCs, were maintained in XF-CIM. C-MSCs generated with XF-CIM showed enlarged round cells, cartilage matrix, and hypertrophic chondrocytes genes elevation in vitro. Transplantation of C-MSCs generated with XF-CIM induced successful bone regeneration in the SCID mouse calvaria defect model. Immunofluorescence staining for human-specific vimentin demonstrated that donor human and host mouse cells cooperatively contributed the bone formation. Besides, the replacement of the cartilage matrix into bone was observed in the early period. These findings suggested that cartilaginous C-MSCs generated with XF-CIM can induce bone regeneration via endochondral ossification.
Epigenetic Regulation of Cardiac Troponin Genes in Pediatric Patients with Heart Failure Supported by Ventricular Assist Device
Authors: Ragusa Rosetta , Di Molfetta Arianna , Del Turco Serena , Cabiati Manuela , Del Ry Silvia , Basta Giuseppina , Mercatanti Alberto , Pitto Letizia , Amodeo Antonio , Trivella Maria Giovanna , Rizzo Milena , Caselli Chiara
Published: October 2021

Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study. miRNA profile was determined in cardiac samples obtained from 13 HF children [median: 29 months; 19 LVEF%; 9 Kg] by NGS before VAD implant (pre-VAD) and at the moment of heart transplant (Post-VAD). Only hsa-miR-199b-5p, hsa-miR-19a-3p, hsa-miR-1246 were differentially expressed at post-VAD when compared to pre-VAD, and validated by real-time PCR. Putative targets of the selected miRNAs were involved in regulation of sarcomere genes, such as cardiac troponin (cTns) complex. The expression levels of fetal ad adult isoforms of cTns resulted significantly higher after VAD in cardiac tissue of HF pediatric patients when compared with HF adults. An in vitro study confirmed a down-regulatory effect of hsa-miR-19a-3p on cTnC expression. The effect of VAD on sarcomere organization through cTn isoform expression may be epigenetically regulated, suggesting for miRNAs a potential role as therapeutic targets to improve heart function in HF pediatric patients.
Development of a Material Design Space for 4D-Printed Bio-Inspired Hygroscopically Actuated Bilayer Structures with Unequal Effective Layer Widths
Authors: Krüger Friederike , Thierer Rebecca , Tahouni Yasaman , Sachse Renate , Wood Dylan , Menges Achim , Bischoff Manfred , Rühe Jürgen
Published: October 2021

(1) Significance of geometry for bio-inspired hygroscopically actuated bilayer structures is well studied and can be used to fine-tune curvatures in many existent material systems. We developed a material design space to find new material combinations that takes into account unequal effective widths of the layers, as commonly used in fused filament fabrication, and deflections under self-weight. (2) For this purpose, we adapted Timoshenko’s model for the curvature of bilayer strips and used an established hygromorphic 4D-printed bilayer system to validate its ability to predict curvatures in various experiments. (3) The combination of curvature evaluation with simple, linear beam deflection calculations leads to an analytical solution space to study influences of Young’s moduli, swelling strains and densities on deflection under self-weight and curvature under hygroscopic swelling. It shows that the choice of the ratio of Young’s moduli can be crucial for achieving a solution that is stable against production errors. (4) Under the assumption of linear material behavior, the presented development of a material design space allows selection or design of a suited material combination for application-specific, bio-inspired bilayer systems with unequal layer widths.
3D-Printed Biodigital Clay Bricks
Authors: Abdallah Yomna K. , Estévez Alberto T.
Published: October 2021

Construction materials and techniques have witnessed major advancements due to the application of digital tools in the design and fabrication processes, leading to a wide array of possibilities, especially in additive digital manufacturing tools and 3D printing techniques, scales, and materials. However, possibilities carry responsibilities with them and raise the question of the sustainability of 3D printing applications in the built environment in terms of material consumption and construction processes: how should one use digital design and 3D printing to achieve minimum material use, minimum production processes, and optimized application in the built environment? In this work, we propose an optimized formal design of “Biodigital Barcelona Clay Bricks” to achieve sustainability in the use of materials. These were achieved by using a bottom-up methodology of biolearning to extract the formal grammar of the bricks that is suitable for their various applications in the built environment as building units, thereby realizing the concept of formal physiology, as well as employing the concept of fractality or pixilation by using 3D printing to create the bricks as building units on an architectural scale. This enables the adoption of this method as an alternative construction procedure instead of conventional clay brick and full-scale 3D printing of architecture on a wider and more democratic scale, avoiding the high costs of 3D printing machines and lengthy processes of the one-step, 3D-printed, full-scale architecture, while also guaranteeing minimum material consumption and maximum forma–function coherency. The “Biodigital Barcelona Clay Bricks” were developed using Rhinoceros 3D and Grasshopper 3D + Plugins (Anemone and Kangaroo) and were 3D printed in clay.
A Bridge between the Breath and the Brain: Synchronization of Respiration, a Pupillometric Marker of the Locus Coeruleus, and an EEG Marker of Attentional Control State
Authors: Melnychuk Michael Christopher , Robertson Ian H. , Plini Emanuele R. G. , Dockree Paul M.
Published: October 2021

Yogic and meditative traditions have long held that the fluctuations of the breath and the mind are intimately related. While respiratory modulation of cortical activity and attentional switching are established, the extent to which electrophysiological markers of attention exhibit synchronization with respiration is unknown. To this end, we examined (1) frontal midline theta-beta ratio (TBR), an indicator of attentional control state known to correlate with mind wandering episodes and functional connectivity of the executive control network; (2) pupil diameter (PD), a known proxy measure of locus coeruleus (LC) noradrenergic activity; and (3) respiration for evidence of phase synchronization and information transfer (multivariate Granger causality) during quiet restful breathing. Our results indicate that both TBR and PD are simultaneously synchronized with the breath, suggesting an underlying oscillation of an attentionally relevant electrophysiological index that is phase-locked to the respiratory cycle which could have the potential to bias the attentional system into switching states. We highlight the LC’s pivotal role as a coupling mechanism between respiration and TBR, and elaborate on its dual functions as both a chemosensitive respiratory nucleus and a pacemaker of the attentional system. We further suggest that an appreciation of the dynamics of this weakly coupled oscillatory system could help deepen our understanding of the traditional claim of a relationship between breathing and attention.
Mechanical Aspects of Angiogenesis
Authors: Kretschmer Maibritt , Rüdiger Daniel , Zahler Stefan
Published: October 2021

Angiogenesis is of high clinical relevance as it plays a crucial role in physiological (e.g., tissue regeneration) and pathological processes (e.g., tumor growth). Besides chemical signals, such as VEGF, the relationship between cells and the extracellular matrix (ECM) can influence endothelial cell behavior during angiogenesis. Previously, in terms of the connection between angiogenesis and mechanical factors, researchers have focused on shear forces due to blood flow. However, it is becoming increasingly important to include the direct influence of the ECM on biological processes, such as angiogenesis. In this context, we focus on the stiffness of the surrounding ECM and the adhesion of cells to the ECM. Furthermore, we highlight the mechanical cues during the main stages of angiogenesis: cell migration, tip and stalk cells, and vessel stabilization. It becomes clear that the different stages of angiogenesis require various chemical and mechanical cues to be modulated by/modulate the stiffness of the ECM. Thus, changes of the ECM during tumor growth represent additional potential dysregulations of angiogenesis in addition to erroneous biochemical signals. This awareness could be the basis of therapeutic approaches to counteract specific processes in tumor angiogenesis.
Artificial Intelligence in Brain Tumour Surgery—An Emerging Paradigm
Authors: Williams Simon , Layard Horsfall Hugo , Funnell Jonathan P. , Hanrahan John G. , Khan Danyal Z. , Muirhead William , Stoyanov Danail , Marcus Hani J.
Published: October 2021

Artificial intelligence (AI) platforms have the potential to cause a paradigm shift in brain tumour surgery. Brain tumour surgery augmented with AI can result in safer and more effective treatment. In this review article, we explore the current and future role of AI in patients undergoing brain tumour surgery, including aiding diagnosis, optimising the surgical plan, providing support during the operation, and better predicting the prognosis. Finally, we discuss barriers to the successful clinical implementation, the ethical concerns, and we provide our perspective on how the field could be advanced.
Replacement of Lost Substance P Reduces Fibrosis in the Diabetic Heart by Preventing Adverse Fibroblast and Macrophage Phenotype Changes
Authors: Widiapradja Alexander , Kasparian Ainsley O. , McCaffrey Samuel L. , Kolb Lauren L. , Imig John D. , Lacey Jessica L. , Melendez Giselle C. , Levick Scott P.
Published: October 2021

Reduced levels of the sensory nerve neuropeptide substance P (SP) have been reported in the diabetic rat heart, the consequence being a loss of cardioprotection in response to ischemic post-conditioning. We considered whether this loss of SP also predisposes the heart to non-ischemic diabetic cardiomyopathy in the form of fibrosis and hypertrophy. We report that diabetic Leprdb/db mice have reduced serum SP and that administration of exogenous replacement SP ameliorated cardiac fibrosis. Cardiac hypertrophy did not occur in Leprdb/db mice. Cardiac fibroblasts exposed to high glucose converted to a myofibroblast phenotype and produced excess extracellular matrix proteins; this was prevented by the presence of SP in the culture media. Cardiac fibroblasts exposed to high glucose produced increased amounts of the receptor for advanced glycation end products, reactive oxygen species and inflammatory cytokines, all of which were prevented by SP. Cultured macrophages assumed an M1 pro-inflammatory phenotype in response to high glucose as indicated by increased TNF-α, CCL2, and IL-6. SP promoted a shift to the reparative M2 macrophage phenotype characterized by arginase-1 and IL-10. Leprdb/db mice showed increased left ventricular M1 phenotype macrophages and an increase in the M1/M2 ratio. Replacement SP in Leprdb/db mice restored a favorable M1 to M2 balance. Together these findings indicate that a loss of SP predisposes the diabetic heart to developing fibrosis. The anti-fibrotic actions of replacement SP involve direct effects on cardiac fibroblasts and macrophages to oppose adverse phenotype changes. This study identifies the potential of replacement SP to treat diabetic cardiomyopathy.
IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization
Authors: Yang Shu , Magnutzki Alexander , Alami Najwa Ouali , Lattke Michael , Hein Tabea Melissa , Scheller Judith Stefanie , Kröger Carsten , Oswald Franz , Yilmazer-Hanke Deniz , Wirth Thomas , Baumann Bernd
Published: October 2021

Alzheimer’s disease (AD) is a common neurodegenerative disease that is accompanied by pronounced neuroinflammatory responses mainly characterized by marked microgliosis and astrogliosis. However, it remains open as to how different aspects of astrocytic and microglial activation affect disease progression. Previously, we found that microglia expansion in the spinal cord, initiated by IKK2/NF-κB activation in astrocytes, exhibits stage-dependent beneficial effects on the progression of amyotrophic lateral sclerosis. Here, we investigated the impact of NF-κB-initiated neuroinflammation on AD pathogenesis using the APP23 mouse model of AD in combination with conditional activation of IKK2/NF-κB signaling in astrocytes. We show that NF-κB activation in astrocytes triggers a distinct neuroinflammatory response characterized by striking astrogliosis as well as prominent microglial reactivity. Immunohistochemistry and Congo red staining revealed an overall reduction in the size and number of amyloid plaques in the cerebral cortex and hippocampus. Interestingly, isolated primary astrocytes and microglia cells exhibit specific marker gene profiles which, in the case of microglia, point to an enhanced plaque clearance capacity. In contrast, direct IKK2/NF-κB activation in microglia results in a pro-inflammatory polarization program. Our findings suggest that IKK2/NF-κB signaling in astrocytes may activate paracrine mechanisms acting on microglia function but also on APP processing in neurons.
Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease
Authors: Macek Jilkova Zuzana , Hilleret Marie Noelle , Gerster Theophile , Sturm Nathalie , Mercey-Ressejac Marion , Zarski Jean-Pierre , Leroy Vincent , Marche Patrice N. , Costentin Charlotte , Decaens Thomas
Published: October 2021

Immune checkpoint molecules (ICM) are critical in maintaining immunologic homeostasis and participate in preventing or promoting autoimmune disease development. Exploring a large panel of intrahepatic inhibitory and stimulatory ICM is necessary for drawing a general picture of the immune alterations in autoimmune hepatitis (AIH). Here, we performed a multiparametric analysis of ICM, including PD-1, TIM3, LAG3, CTLA-4, OX40 and 4-1BB, and we determined their expression on intrahepatic lymphocyte subsets in untreated and in treated patients with AIH in comparison to normal liver tissue. AIH patient-derived liver tissue revealed the overexpression of ICM, mainly PD-1 and 4-1BB, as well as the strong correlation between PD-1+ CD8+ T-cell abundance and severity of AIH (alanine transaminase and aspartate transaminase levels). Our results show that the ICM play an important role in the loss of immune homeostasis in the liver, providing an attractive approach to investigate their role as targets for effective therapeutic interventions.
In Silico Evaluation of Natural Compounds for an Acidic Extracellular Environment in Human Breast Cancer
Authors: Park YoungJoon , Jeong Jaekwang , Seong Shin , Kim Wonnam
Published: October 2021

The survival rates for breast cancer (BC) have improved in recent years, but resistance, metastasis, and recurrence still remain major therapeutic challenges for BC. The acidic tumor microenvironment (TME) has attracted attention because of its association with tumorigenesis, metastasis, drug resistance, and immune surveillance. In this study, we evaluated natural compounds from traditional herbal medicine used to treat cancer that selectively target genes regulated by extracellular acidosis. We integrated four transcriptomic data including BC prognostic data from The Cancer Genome Atlas database, gene expression profiles of MCF-7 cells treated with 102 natural compounds, patterns of gene profiles by acidic condition, and single-cell RNA-sequencing from BC patient samples. Bruceine D (BD) was predicted as having the highest therapeutic potential, having an information gain (IG) score of 0.24, to regulate reprogrammed genes driven by acidosis affecting the survival of BC patients. BD showed the highest IG on EMT (IG score: 0.11) and invasion (IG score: 0.1) compared to the other phenotypes with the CancerSEA database. BD also demonstrated therapeutic potential by interfering with the tumor cell–TME interactions by reducing the amyloid beta precursor protein and CD44 expression. Therefore, BD is a potential candidate to target the acidic TME induced metastatic process in BC.
Molecular Determinants for RNA Release into Extracellular Vesicles
Authors: Mosbach Marie-Luise , Pfafenrot Christina , von Strandmann Elke Pogge , Bindereif Albrecht , Preußer Christian
Published: October 2021

Extracellular vesicles (EVs) are important for intercellular communication and act as vehicles for biological material, such as various classes of coding and non-coding RNAs, a few of which were shown to selectively target into vesicles. However, protein factors, mechanisms, and sequence elements contributing to this specificity remain largely elusive. Here, we use a reporter system that results in different types of modified transcripts to decipher the specificity determinants of RNAs released into EVs. First, we found that small RNAs are more efficiently packaged into EVs than large ones, and second, we determined absolute quantities for several endogenous RNA transcripts in EVs (U6 snRNA, U1 snRNA, Y1 RNA, and GAPDH mRNA). We show that RNA polymerase III (pol III) transcripts are more efficiently secreted into EVs compared to pol II-derived transcripts. Surprisingly, our quantitative analysis revealed no RNA accumulation in the vesicles relative to the total cellular levels, based on both overexpressed reporter transcripts and endogenous RNAs. RNA appears to be EV-associated only at low copy numbers, ranging between 0.02 and 1 molecule per EV. This RNA association may reflect internal EV encapsulation or a less tightly bound state at the vesicle surface.