bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk and Safety Management in Physical Education: A Study of Teachers' Practice Perspectives
Authors: Porsanger Lise , Magnussen Leif Inge
Published: April 2021

The aim of this article is to explore and understand teachers' risk and safety management (RSM) practices in physical education (PE) programs in Norway. A survey questionnaire and semistructured interviews were therefore used to generate quantitative data on trends from a larger sample of teachers (n= 698) and rich in-depth qualitative data concerning teachers' (n= 17) practices. By providing the teachers' perspectives, a better understanding of the complexity of RSM in PE may be possible. The results from both the survey and interviews suggest that teachers employ multiple strategies: from safety procedures, complying to compulsory risk measures, to the use of common sense in their RSM practices. The interviewees, on the other hand, initially claim that their RSM practice is quite scarce and, in some respects, not appropriate for PE. They emphasize measures that cater to the students' needs and modification to physical activities in their teaching. However, the interview data suggest that teachers do not primarily conceptualize this part of their practice as RSM but as measures of other pedagogical concerns. Combined, the results from both the survey and the interviews may characterize a RSM practice that relies on teaching experience and the use of discretion. The results in this article both converge and diverge and emphasize the importance of multiple data sources in investigating teachers' RSM practices.
Association of Ancillary Pathology Findings in Non-neoplastic Renal Parenchyma and Renal Outcomes of Robotic-Assisted Partial Nephrectomy
Authors: Geldmaker Laura E. , Kahn Amanda E. , Parikh Kevin A. , Porter Ivan E. , Haehn Daniela A. , Bajalia Essa M. , Zhai Qihui , Ball Colleen T. , Thiel David D.
Published: April 2021

Background: To evaluate robotic-assisted partial nephrectomy (RAPN) renal outcomes associated with ancillary pathology findings in non-neoplastic renal parenchymal tissue.

Methods: Tissue samples from 378 RAPNs were analyzed for glomerular disease (GD), vascular disease (VD), and tubulointerstitial disease (TD). One hundred and fifty-two patients were excluded due to insufficient non-neoplastic tissue for analysis and 4 patients were excluded due to calyceal diverticulum. Non-neoplastic tissue was evaluated for GD (negative, moderate, or global), VD (absent, mild, moderate, or severe), and TD (present or absent). Associations of ancillary pathology factors with patient characteristics were explored using the non-parametric Kendall tau-test and propensity score adjusted longitudinal mixed effects regression models were used to evaluate associations of these pathology factors with changes in estimated glomerular filtration rate (eGFR) following RAPN.

Results: One hundred and fifty-three (68.9%) patients had hypertension and 50 (22.5%) patients had diabetes. The majority of patients did not have any GD (N = 158, 71.2%) or TD (N = 186, 83.8%) while 129 (58.1%) had VD. VD was categorized as absent (N = 93, 41.9%), mild (N = 45, 20.3%), moderate (N = 76, 34.2%), and severe (N = 8, 6.8%). Older age (P = 0.018), hypertension (P < 0.001), and high grade MAP score (P = 0.047) were associated with a higher number of ancillary pathology factors. High grade MAP score (P = 0.03, P = 0.002) and hypertension (P = 0.02, P < 0.001) were individually associated with GD severity and VD severity, respectively. Older age was also individually associated with VD severity (P = 0.002) and hypertension was associated with TD (P = 0.04). Moderate-to-severe VD was associated with a worse change in eGFR from pre-RAPN to 1-month post-RAPN compared to those with mild or no VD (difference in mean change, −3.4 ml/kg/1.73m2; 95% CI, −6.6 to −0.2 ml/kg/1.73m2; P = 0.036).

Conclusions: Moderate-to-severe VD in non-neoplastic renal parenchyma is associated with post-operative changes in eGFR. Older age, hypertension, and high grade MAP scores are associated with the number of ancillary pathologies observed in RAPN specimens.
Factors Affecting the Welfare of Unweaned Dairy Calves Destined for Early Slaughter and Abattoir Animal-Based Indicators Reflecting Their Welfare On-Farm
Authors: Boyle Laura A. , Mee John F.
Published: April 2021

In many dairy industries, but particularly those that are pasture-based and have seasonal calving, “surplus calves,” which are mostly male, are killed at a young age because they are of low value and it is not economically viable to raise them. Such calves are either killed on farm soon after birth or sent for slaughter at an abattoir. In countries where calves are sent for slaughter the age ranges from 3-4 days (New Zealand and Australia; “bobby calves”) to 3-4 weeks (e.g., Ireland); they are not weaned. All calves are at the greatest risk of death in the 1st month of life but when combined with their low value, this makes surplus calves destined for early slaughter (i.e., <1 month of age) particularly vulnerable to poor welfare while on-farm. The welfare of these calves may also be compromised during transport and transit through markets and at the abattoir. There is growing recognition that feedback to farmers of results from animal-based indicators (ABI) of welfare (including health) collected prior to and after slaughter can protect animal welfare. Hence, the risk factors for poor on-farm, in-transit and at-abattoir calf welfare combined with an ante and post mortem (AM/PM) welfare assessment scheme specific to calves <1 month of age are outlined. This scheme would also provide an evidence base with which to identify farms on which such animals are more at risk of poor welfare. The following ABIs, at individual or batch level, are proposed: AM indicators include assessment of age (umbilical maturity), nutritional status (body condition, dehydration), behavioral status (general demeanor, posture, able to and stability while standing and moving, shivering, vocalizations, oral behaviors/cross-sucking, fearfulness, playing), and evidence of disease processes (locomotory ability [lameness], cleanliness/fecal soiling [scour], injuries hairless patches, swellings, wounds], dyspnoea/coughing, nasal/ocular discharge, navel swelling/discharge); PM measures include assessment of feeding adequacy (abomasal contents, milk in rumen, visceral fat reserves) and evidence of disease processes (omphalitis, GIT disorders, peritonitis, abscesses [internal and external], arthritis, septicaemia, and pneumonia). Based on similar models in other species, this information can be used in a positive feedback loop not only to protect and improve calf welfare but also to inform on-farm calf welfare management plans, support industry claims regarding animal welfare and benchmark welfare performance nationally and internationally.
Prediction of Tensile Strain Capacity for X52 Steel Pipeline Materials Using the Extended Finite Element Method
Authors: Elyasi Nahid , Shahzamanian Mohammadmehdi , Lin Meng , Westover Lindsey , Li Yong , Kainat Muntaseer , Yoosef-Ghodsi Nader , Adeeb Samer
Published: April 2021

Strain-based design (SBD) plays an important role in pipeline design and assessment of pipelines subjected to geo-hazards. Under such hazards, a pipe can be subjected to substantial plastic strains, leading to tensile failure at locations of girth weld flaws. For SBD, the finite element method (FEM) can be a reliable tool to calculate the tensile strain capacity (TSC) for better design in pipelines. This study aims to investigate the ductile fracture properties for specific vintage pipeline steel (API 5L grade of X52) using the extended finite element method (XFEM). Eight full-scale tests were simulated using the commercial finite element analysis software ABAQUS Version 6.17. Maximum principal strain is used to assess the damage initiation using the cohesive zone model (CZM) when the crack evolution is evaluated by fracture energy release. A proper set of damage parameters for the X52 materials was calibrated based on the ability of the model to reproduce the experimental results. These experimental results included the tensile strain, applied load, endplate rotation, and crack mouth opening displacement (CMOD). This study describes a methodology for validation of the XFEM and the proper damage parameters required to model crack initiation and propagation in X52 grades of pipeline.
Free Vibration Analysis of Rotating Beams Based on the Modified Couple Stress Theory and Coupled Displacement Field
Authors: Babaei Alireza , Arabghahestani Masoud
Published: April 2021

In this paper, transverse vibration analysis of rotating micro-beam is investigated based on the modified couple stress theory. The simply-supported micro-beam is modeled utilizing Euler-Bernoulli and Timoshenko beam theories. The system is rotating around a fixed axis perpendicular to the axial direction of the beam. For the first time, displacement filed is introduced as a coupled field to the translational field. In other words, the mentioned rotational displacement field is expressed as a proportional function of translational displacement field using first (axial), second (lateral), and third (angular or rotational) velocity factors. Utilizing Hamilton’s approach as a variational method, dynamic-vibration equations of motion of the proposed model are derived. Galerkin’s method is adopted to solve the equation corresponding to the Euler–Bernoulli and Timoshenko beams. For the case considering shear deformation effects, Navier method is chosen. For evaluation of current results and models, they are compared with those available at the benchmark. In this paper; effects of slenderness ratio, axial, lateral, and angular velocity factors, and rotations of the beam on the frequency are reported. Based on the results presented, mentioned factors should be counted in the analysis and design of such rotating micro-systems.
PET Imaging of GPR44 by Antagonist [11C]MK-7246 in Pigs
Authors: Cheung Pierre , Zhang Bo , Puuvuori Emmi , Estrada Sergio , Amin Mohammad A. , Ye Sofie , Korsgren Olle , Odell Luke R. , Eriksson Jonas , Eriksson Olof
Published: April 2021

A validated imaging marker for beta-cell mass would improve understanding of diabetes etiology and enable new strategies in therapy development. We previously identified the membrane-spanning protein GPR44 as highly expressed and specific to the beta cells of the pancreas. The selective GPR44 antagonist MK-7246 was radiolabeled with carbon-11 and the resulting positron-emission tomography (PET) tracer [11C]MK-7246 was evaluated in a pig model and in vitro cell lines. The [11C]MK-7246 compound demonstrated mainly hepatobiliary excretion with a clearly defined pancreas, no spillover from adjacent tissues, and pancreatic binding similar in magnitude to the previously evaluated GPR44 radioligand [11C]AZ12204657. The binding could be blocked by preadministration of nonradioactive MK-7246, indicating a receptor-binding mechanism. [11C]MK-7246 showed strong potential as a PET ligand candidate for visualization of beta-cell mass (BCM) and clinical translation of this methodology is ongoing.
Variable-Angle Spectroscopic Ellipsometry of Graphene-Based Films
Authors: Politano Grazia Giuseppina , Versace Carlo
Published: April 2021

A review of the authors’ research works on Variable-Angle Spectroscopy (VASE) of graphene-based films is presented. The interaction of graphene oxide (GO) with magnetron-sputtered metals is a promising research area. VASE optical models of GO thin films deposited on magnetron-sputtered titanium (Ti), silver (Ag) and gold (Au) are discussed. Moreover, the optical properties of graphene nanoplatelet (GNPS) films and reduced graphene oxide (RGO) stabilized with Poly(Sodium 4-Styrenesulfonate) (PSS) films, which are less studied graphene-related materials, are shown. Finally, different optical behaviors of chemical vapor deposition (CVD)-grown monolayer, bilayer, and trilayer graphene films on silicon and polyethylene terephthalate (PET) substrates are recapitulated.
BOOSTR: A Dataset for Accelerator Control Systems
Authors: Kafkes Diana , St. John Jason
Published: April 2021

The Booster Operation Optimization Sequential Time-series for Regression (BOOSTR) dataset was created to provide a cycle-by-cycle time series of readings and settings from instruments and controllable devices of the Booster, Fermilab’s Rapid-Cycling Synchrotron (RCS) operating at 15 Hz. BOOSTR provides a time series from 55 device readings and settings that pertain most directly to the high-precision regulation of the Booster’s gradient magnet power supply (GMPS). To our knowledge, this is one of the first well-documented datasets of accelerator device parameters made publicly available. We are releasing it in the hopes that it can be used to demonstrate aspects of artificial intelligence for advanced control systems, such as reinforcement learning and autonomous anomaly detection.
Towards a Live Feedback Training System: Interchangeability of Orbbec Persee and Microsoft Kinect for Exercise Monitoring
Authors: Venek Verena , Kremser Wolfgang , Stöggl Thomas
Published: April 2021

Many existing motion sensing applications in research, entertainment and exercise monitoring are based on the Microsoft Kinect and its skeleton tracking functionality. With the Kinect’s development and production halted, researchers and system designers are in need of a suitable replacement. We investigated the interchangeability of the discontinued Kinect v2 and the all-in-one, image-based motion tracking system Orbbec Persee for the use in an exercise monitoring system prototype called ILSE. Nine functional training exercises were performed by six healthy subjects in front of both systems simultaneously. Comparing the systems’ internal tracking states from ’not tracked’ to ‘tracked’ showed that the Persee system is more confident during motion sequences, while the Kinect is more confident for hip and trunk joint positions. Assessing the skeleton tracking robustness, the Persee’s tracking of body segment lengths was more consistent. Furthermore, we used both skeleton datasets as input for the ILSE exercise monitoring including posture recognition and repetition-counting. Persee data from exercises with lateral movement and in uncovered full-body frontal view provided the same results as Kinect data. The Persee further preferred tracking of quasi-static lower limb motions and tight-fitting clothes. With these limitations in mind, we find that the Orbbec Persee is a suitable replacement for the Microsoft Kinect for motion sensing within the ILSE exercise monitoring system.
Hybrid LoRa-IEEE 802.11s Opportunistic Mesh Networking for Flexible UAV Swarming
Authors: Davoli Luca , Pagliari Emanuele , Ferrari Gianluigi
Published: April 2021

Unmanned Aerial Vehicles (UAVs) and small drones are nowadays being widely used in heterogeneous use cases: aerial photography, precise agriculture, inspections, environmental data collection, search-and-rescue operations, surveillance applications, and more. When designing UAV swarm-based applications, a key “ingredient” to make them effective is the communication system (possible involving multiple protocols) shared by flying drones and terrestrial base stations. When compared to ground communication systems for swarms of terrestrial vehicles, one of the main advantages of UAV-based communications is the presence of direct Line-of-Sight (LOS) links between flying UAVs operating at an altitude of tens of meters, often ensuring direct visibility among themselves and even with some ground Base Transceiver Stations (BTSs). Therefore, the adoption of proper networking strategies for UAV swarms allows users to exchange data at distances (significantly) longer than in ground applications. In this paper, we propose a hybrid communication architecture for UAV swarms, leveraging heterogeneous radio mesh networking based on long-range communication protocols—such as LoRa and LoRaWAN—and IEEE 802.11s protocols. We then discuss its strengths, constraints, viable implementation, and relevant reference use cases.
Applying the Horizontal Visibility Graph Method to Study Irreversibility of Electromagnetic Turbulence in Non-Thermal Plasmas
Authors: Acosta-Tripailao Belén , Pastén Denisse , Moya Pablo S.
Published: April 2021

One of the fundamental open questions in plasma physics is the role of non-thermal particles distributions in poorly collisional plasma environments, a system that is commonly found throughout the Universe, e.g., the solar wind and the Earth’s magnetosphere correspond to natural plasma physics laboratories in which turbulent phenomena can be studied. Our study perspective is born from the method of Horizontal Visibility Graph (HVG) that has been developed in the last years to analyze time series avoiding the tedium and the high computational cost that other methods offer. Here, we build a complex network based on directed HVG technique applied to magnetic field fluctuations time series obtained from Particle In Cell (PIC) simulations of a magnetized collisionless plasma to distinguish the degree distributions and calculate the Kullback–Leibler Divergence (KLD) as a measure of relative entropy of data sets produced by processes that are not in equilibrium. First, we analyze the connectivity probability distribution for the undirected version of HVG finding how the Kappa distribution for low values of κ tends to be an uncorrelated time series, while the Maxwell–Boltzmann distribution shows a correlated stochastic processes behavior. Subsequently, we investigate the degree of temporary irreversibility of magnetic fluctuations that are self-generated by the plasma, comparing the case of a thermal plasma (described by a Maxwell–Botzmann velocity distribution function) with non-thermal Kappa distributions. We have shown that the KLD associated to the HVG is able to distinguish the level of reversibility that is associated to the thermal equilibrium in the plasma, because the dissipative degree of the system increases as the value of κ parameter decreases and the distribution function departs from the Maxwell–Boltzmann equilibrium.
Impact of Advanced Load-Frequency Control on Optimal Size of Battery Energy Storage in Islanded Microgrid System
Authors: Sitompul Sandro , Fujita Goro
Published: April 2021

The application of battery energy storage (BES) in microgrid systems has attracted much attention in recent years. It is because the BES is able to store excess power and discharge its power when needed. In islanded microgrid systems, BES is starting to be considered as a unit that can regulate the system frequency. The control used in the BES to display frequency regulation performance is called load-frequency control (LFC). However, this participation resulted in the large size of the battery and high expansion planning cost. In this paper, an advanced LFC control that has frequency limitation compared to traditional LFC is proposed. The proposed control implies droop control as the base and has frequency limitations. Compared to the traditional LFC, the proposed control can reduce the system expansion planning costs. A performance simulation was done to validate battery performance. The results of the numerical simulation showed that the proposed control participated in reducing the operation cost. It directly led to a reduction in the expansion planning cost. A study of battery selection was conducted to draw the practicality of the BES sizing solutions.
Drivers and Barriers for a Circular Economy (CE) Implementation in Poland—A Case Study of Raw Materials Recovery Sector
Authors: Smol Marzena , Marcinek Paulina , Koda Eugeniusz
Published: April 2021

Mobilizing industry and transforming industrial sectors to a circular economy (CE) is one of the key areas of activities in the European Green Deal (EGD)—the newest strategy of economic growth in European Union (EU). In the CE, the raw materials that can be recovered from various waste streams play a key role, therefore, recommendations for their management were developed, both at the European and national level. In Poland, the raw material recovery sector is one of the strategic sectors (key industries) described in several documents determining the further directions of economic growth in the country. This paper presents the revision of these documents and guidelines for the implementation of the CE in the raw material recovery sector. The scope of the paper also includes a description of the current state of the raw materials recovery sector and its return, supported by the analysis of drivers and barriers in its further development. In previous years, a dynamic development of the recovery industry was observed, followed by formation of new companies (dominated by medium-sized companies comprising ~50% of entities in the sector) and increasing amount of people employed (~70,700 people). A growing level of processing of secondary raw materials with the use of more and more innovative technologies has been observed, which could contribute to the improvement of the level of innovation of the national economy. There also some barriers, such as the lack of sufficiently developed industrial symbiosis (IS) and long-term support for the implementation of recovery technologies. The growing ecological awareness of society and enterprises themselves, as well as the growing belief in the importance of resource recovery for environmental protection, suggest the possibility of subsequent development of the raw materials recovery sector. Further actions in this field will be taken to strengthen the implementation of the CE in the country.
Self-Excited Acoustical System Frequency Monitoring for Refractory Concrete under Uniaxial Compression
Authors: Kieliba Ilona , Dominik Ireneusz , Lalik Krzysztof , Tonnesen Thorsten , Szczerba Jacek , Telle Reiner
Published: April 2021

The characterization of materials, stress and fatigue state monitoring based on the acoustoelastic principle are gaining widespread attention in recent years, mainly due to their advantages such as high sensitivity and non-destructive character. This article presents the application of a non-destructive acoustic method to test the degree of degradation of materials with which the heating boiler is coated. The combustion chamber is covered in materials when the temperature of the process itself increases, and has a very positive effect on fuel combustion. Unfortunately, with the passage of time, such materials undergo gradation. This article describes an innovative measuring system that has been successfully applied to monitor changes in resonance frequency under uniaxial compression in refractory grade material, which by definition is characterized by a high level of heterogeneity with a network of pre-existing cracks. The paper indicates that both stress and elasticity coefficients have an impact on the vibration frequency of the measuring system. Initial research was conducted to qualitatively determine the influence of these parameters on the measured frequency of the system.
Does Economic Structure Differentiate the Achievements towards Energy SDG in the EU?
Authors: Cyrek Magdalena , Cyrek Piotr
Published: April 2021

Energy sustainability constitutes an important goal for development, as declared at the global and the European levels. Some conditions decisive for energy performance, as suggested by the Environmental Kuznets Curve (EKC) hypothesis, may be specified by the sectoral structure of production, as industries vary in the intensity of energy consumption. Nevertheless, sustainability is not automatically induced along with economic development and it is important to identify its determinants. The aim of the study is to empirically verify whether the sectoral structure of an economy differentiates energy sustainability within 28 European Union member states (the EU-28). To fulfil the task, a static approach was adopted and such taxonomic methods as the Ward agglomeration method and linear ordering based on the Hellwig synthetic measure were used. The hypothesis concerning the essential role of structural features in energy achievements was verified by a one-way analysis of variance. Our results do not confirm the decisive role of economic structure in energy performance for the EU-28 states; however, they suggest some complex relationships. The interference between energy performance and sectoral structure mostly concerned primary and final energy consumptions and energy poverty, as well as the shares of agriculture, industry, traditional services and finance in total production. The findings reveal a need for further research into the potential interlinkages between different dimensions of sustainable development (SD).
New Insights into Crust and upper Mantle Structure in Guangdong Province, China and Its Geothermal Implications
Authors: Kuang Jian , Qi Shihua , Hu Xiangyun
Published: April 2021

Southeast Asia contains significant natural geothermal resources. However, the mechanism for generating geothermal anomalies by the crust–mantle structure still needs to define. In this study, we focused on Guangdong Province, China. We conducted three magnetotelluric profiles to interpret the crust and upper mantle structure beneath the Guangdong Province and its geothermal implications. Based on data analysis results, a two-dimension inversion was conducted on the dataset. The inversion model revealed that there is a presence of upwelling channels, and some channels are connected with shallow crustal fault zone; the thickness of crust and lithosphere in Guangdong Province is relatively thin. Such a special crust and upper mantle structure form high surface heat flow. Merged with previous research, our results imply that massive Late Mesozoic granites, which contain high radioactive heat generating elements, are distributed on the surface and underground of Guangdong Province. Based on the correlation between high radioactive Late Mesozoic granites, crust-upper mantle structure, surface heat flow, and locations of natural hot springs, we established a geothermal conceptual model to visualize the origin of a current geophysical and geothermal anomaly in Guangdong Province.
Effects of Vegetation Type on Soil Shear Strength in Fengyang Mountain Nature Reserve, China
Authors: Liu Xin , Cheng Xuefei , Wang Nan , Meng Miaojing , Jia Zhaohui , Wang Jinping , Ma Shilin , Tang Yingzhou , Li Chong , Zhai Lu , Zhang Bo , Zhang Jinchi
Published: April 2021

Shear strength is an important mechanical property of soil, as its mechanical function plays critical roles in reducing land degradation and preventing soil erosion. However, shear strength may be affected by vegetation type through changes in the soil and root patterns. To understand the influences of different types of vegetation on shear strength, the soil shear indices of three typical vegetation types (broad-leaved forest, coniferous broad-leaved mixed forest, and grassland) were studied and evaluated at the Fengyang Mountain Nature Reserve, China. We employed a direct shear apparatus to measure the soil shear resistance index. We quantified the soil porosity, moisture content, and composition of particle size to determine the properties of the soil, and a root scanner was used to quantify the root index. The results revealed that there were significant differences in shear resistance indices at the stand level. Between the three vegetation types, the internal friction angle of the broad-leaved forest was the largest and the cohesion was the smallest. The soil moisture content and porosity of the coniferous broad-leaved mixed forest were higher than those of the broad-leaved forest, and the root volume density (RVD/cm3) of the broad-leaved forest was higher than that of the coniferous and broad-leaved mixed forest and grassland. Structural equation modeling results show that the soil particle size and root characteristics indirectly impacted the soil water content by affecting porosity, which finally affected shear strength. In general, there were significant differences in soil properties and plant root indices between the different stands, which had an impact on soil shear strength.
Loud Music and Leisure Noise Is a Common Cause of Chronic Hearing Loss, Tinnitus and Hyperacusis
Authors: Pienkowski Martin
Published: April 2021

High sound levels capable of permanently damaging the ear are experienced not only in factories and war zones but in concert halls, nightclubs, sports stadiums, and many other leisure environments. This review summarizes evidence that loud music and other forms of “leisure noise” are common causes of noise-induced hearing loss, tinnitus, and hyperacusis, even if audiometric thresholds initially remain within clinically normal limits. Given the huge global burden of preventable noise-induced hearing loss, noise limits should be adopted in a much broader range of settings, and education to promote hearing conservation should be a higher public health priority.
JDP2, a Novel Molecular Key in Heart Failure and Atrial Fibrillation?
Authors: Euler Gerhild , Kockskämper Jens , Schulz Rainer , Parahuleva Mariana S.
Published: April 2021

Heart failure (HF) and atrial fibrillation (AF) are two major life-threatening diseases worldwide. Causes and mechanisms are incompletely understood, yet current therapies are unable to stop disease progression. In this review, we focus on the contribution of the transcriptional modulator, Jun dimerization protein 2 (JDP2), and on HF and AF development. In recent years, JDP2 has been identified as a potential prognostic marker for HF development after myocardial infarction. This close correlation to the disease development suggests that JDP2 may be involved in initiation and progression of HF as well as in cardiac dysfunction. Although no studies have been done in humans yet, studies on genetically modified mice impressively show involvement of JDP2 in HF and AF, making it an interesting therapeutic target.
Towards Novel Treatments for Schizophrenia: Molecular and Behavioural Signatures of the Psychotropic Agent SEP-363856
Authors: Begni Veronica , Sanson Alice , Luoni Alessia , Sensini Federica , Grayson Ben , Munni Syeda , Neill Joanna C. , Riva Marco A.
Published: April 2021

Schizophrenia is a complex psychopathology whose treatment is still challenging. Given the limitations of existing antipsychotics, there is urgent need for novel drugs with fewer side effects. SEP-363856 (SEP-856) is a novel psychotropic agent currently under phase III clinical investigation for schizophrenia treatment. In this study, we investigated the ability of an acute oral SEP-856 administration to modulate the functional activity of specific brain regions at basal levels and under glutamatergic or dopaminergic-perturbed conditions in adult rats. We found that immediate-early genes (IEGs) expression was strongly upregulated in the prefrontal cortex and, to a less extent, in the ventral hippocampus, suggesting an activation of these regions. Furthermore, SEP-856 was effective in preventing the hyperactivity induced by an acute injection of phencyclidine (PCP), but not of d-amphetamine (AMPH). The compound effectively normalized the PCP-induced increase in IEGs expression in the PFC at all doses tested, whereas only the highest dose determined the major modulations on AMPH-induced changes. Lastly, SEP-856 acute administration corrected the cognitive deficits produced by subchronic PCP administration. Taken together, our data provide further insights on SEP-856, suggesting that modulation of the PFC may represent an important mechanism for the functional and behavioural activity of this novel compound.
Chronic Administrations of Guanfacine on Mesocortical Catecholaminergic and Thalamocortical Glutamatergic Transmissions
Authors: Fukuyama Kouji , Nakano Tomosuke , Shiroyama Takashi , Okada Motohiro
Published: April 2021

It has been established that the selective α2A adrenoceptor agonist guanfacine reduces hyperactivity and improves cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD). The major mechanisms of guanfacine are considered to involve the activation of the postsynaptic α2A adrenoceptor of glutamatergic pyramidal neurons in the frontal cortex, but the effects of chronic guanfacine administration on catecholaminergic and glutamatergic transmissions associated with the orbitofrontal cortex (OFC) are yet to be clarified. The actions of guanfacine on catecholaminergic transmission, the effects of acutely local and systemically chronic (for 7 days) administrations of guanfacine on catecholamine release in pathways from the locus coeruleus (LC) to OFC, the ventral tegmental area (VTA) and reticular thalamic-nucleus (RTN), from VTA to OFC, from RTN to the mediodorsal thalamic-nucleus (MDTN), and from MDTN to OFC were determined using multi-probe microdialysis with ultra-high performance liquid chromatography. Additionally, the effects of chronic guanfacine administration on the expression of the α2A adrenoceptor in the plasma membrane fraction of OFC, VTA and LC were examined using a capillary immunoblotting system. The acute local administration of therapeutically relevant concentrations of guanfacine into the LC decreased norepinephrine release in the OFC, VTA and RTN without affecting dopamine release in the OFC. Systemically, chronic administration of therapeutically relevant doses of guanfacine for 14 days increased the basal release of norepinephrine in the OFC, VTA, RTN, and dopamine release in the OFC via the downregulation of the α2A adrenoceptor in the LC, OFC and VTA. Furthermore, systemically, chronic guanfacine administration did not affect intrathalamic GABAergic transmission, but it phasically enhanced thalamocortical glutamatergic transmission. The present study demonstrated the dual actions of guanfacine on catecholaminergic transmission—acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions of guanfacine probably contribute to the clinical effects of guanfacine against ADHD.
Interleukin 6 and Aneurysmal Subarachnoid Hemorrhage. A Narrative Review
Authors: Simon Matthias , Grote Alexander
Published: April 2021

Interleukin 6 (IL-6) is a prominent proinflammatory cytokine. Neuroinflammation in general, and IL-6 signaling in particular, appear to play a major role in the pathobiology and pathophysiology of aneurysm formation and aneurysmal subarachnoid hemorrhage (SAH). Most importantly, elevated IL-6 CSF (rather than serum) levels appear to correlate with delayed cerebral ischemia (DCI, “vasospasm”) and secondary (“vasospastic”) infarctions. IL-6 CSF levels may also reflect other forms of injury to the brain following SAH, i.e., early brain damage and septic complications of SAH and aneurysm treatment. This would explain why many researchers have found an association between IL-6 levels and patient outcomes. These findings clearly suggest CSF IL-6 as a candidate biomarker in SAH patients. However, at this point, discrepant findings in variable study settings, as well as timing and other issues, e.g., defining proper clinical endpoints (i.e., secondary clinical deterioration vs. angiographic vasospasm vs. secondary vasospastic infarct) do not allow for its routine use. It is also tempting to speculate about potential therapeutic measures targeting elevated IL-6 CSF levels and neuroinflammation in SAH patients. Corticosteroids and anti-platelet drugs are indeed used in many SAH cases (not necessarily with the intention to interfere with detrimental inflammatory signaling), however, no convincing benefit has been demonstrated yet. The lack of a robust clinical perspective against the background of a relatively large body of data linking IL-6 and neuroinflammation with the pathophysiology of SAH is somewhat disappointing. One underlying reason might be that most relevant studies only report correlative data. The specific molecular pathways behind elevated IL-6 levels in SAH patients and their various interactions still remain to be delineated. We are optimistic that future research in this field will result in a better understanding of the role of neuroinflammation in the pathophysiology of SAH, which in turn, will translate into the identification of suitable biomarkers and even potential therapeutic targets.
Natural Compounds as Therapeutic Agents: The Case of Human Topoisomerase IB
Authors: Ottaviani Alessio , Iacovelli Federico , Fiorani Paola , Desideri Alessandro
Published: April 2021

Natural products are widely used as source for drugs development. An interesting example is represented by natural drugs developed against human topoisomerase IB, a ubiquitous enzyme involved in many cellular processes where several topological problems occur due the formation of supercoiled DNA. Human topoisomerase IB, involved in the solution of such problems relaxing the DNA cleaving and religating a single DNA strand, represents an important target in anticancer therapy. Several natural compounds inhibiting or poisoning this enzyme are under investigation as possible new drugs. This review summarizes the natural products that target human topoisomerase IB that may be used as the lead compounds to develop new anticancer drugs. Moreover, the natural compounds and their derivatives that are in clinical trial are also commented on.
Hydroxyapatite-Coated SPIONs and Their Influence on Cytokine Release
Authors: Friedrich Bernhard , Auger Jean-Philippe , Dutz Silvio , Cicha Iwona , Schreiber Eveline , Band Julia , Boccacccini Aldo R. , Krönke Gerhard , Alexiou Christoph , Tietze Rainer
Published: April 2021

Hydroxyapatite- or calcium phosphate-coated iron oxide nanoparticles have a high potential for use in many biomedical applications. In this study, a co-precipitation method for the synthesis of hydroxyapatite-coated nanoparticles (SPIONHAp), was used. The produced nanoparticles have been characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, Fourier transform infrared spectrometry, atomic emission spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy. The results showed a successful synthesis of 190 nm sized particles and their stable coating, resulting in SPIONHAp. Potential cytotoxic effects of SPIONHAp on EL4, THP-1, and Jurkat cells were tested, showing only a minor effect on cell viability at the highest tested concentration (400 µg Fe/mL). The results further showed that hydroxyapatite-coated SPIONs can induce minor TNF-α and IL-6 release by murine macrophages at a concentration of 100 µg Fe/mL. To investigate if and how such particles interact with other substances that modulate the immune response, SPIONHAp-treated macrophages were incubated with LPS (lipopolysaccharides) and dexamethasone. We found that cytokine release in response to these potent pro- and anti-inflammatory agents was modulated in the presence of SPIONHAp. Knowledge of this behavior is important for the management of inflammatory processes following in vivo applications of this type of SPIONs.
In Vitro Characterization of Neutralizing Hen Antibodies to Coxsackievirus A16
Authors: Mwale Pharaoh Fellow , Lee Chi-Hsin , Huang Peng-Nien , Tseng Sung-Nien , Shih Shin-Ru , Huang Hsin-Yuan , Leu Sy-Jye , Huang Yun-Ju , Chiang Liao-Chun , Mao Yan-Chiao , Wang Wei-Chu , Yang Yi-Yuan
Published: April 2021

Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease (HFMD). Children aged <5 years are the most affected by CA16 HFMD globally. Although clinical symptoms of CA16 infections are usually mild, severe complications, such as aseptic meningitis or even death, have been recorded. Currently, no vaccine or antiviral therapy for CA16 infection exists. Single-chain variable fragment (scFv) antibodies significantly inhibit viral infection and could be a potential treatment for controlling the infection. In this study, scFv phage display libraries were constructed from splenocytes of a laying hen immunized with CA16-infected lysate. The pComb3X vector containing the scFv genes was introduced into ER2738 Escherichia coli and rescued by helper phages to express scFv molecules. After screening with five cycles of bio-panning, an effective scFv antibody showing favorable binding activity to proteins in CA16-infected lysate on ELISA plates was selected. Importantly, the selected scFv clone showed a neutralizing capability against the CA16 virus and cross-reacted with viral proteins in EV71-infected lysate. Intriguingly, polyclonal IgY antibody not only showed binding specificity against proteins in CA16-infected lysate but also showed significant neutralization activities. Nevertheless, IgY-binding protein did not cross-react with proteins in EV71-infected lysate. These results suggest that the IgY- and scFv-binding protein antibodies provide protection against CA16 viral infection in in vitro assays and may be potential candidates for treating CA16 infection in vulnerable young children.
Temozolomide Induces the Acquisition of Invasive Phenotype by O6-Methylguanine-DNA Methyltransferase (MGMT)+ Glioblastoma Cells in a Snail-1/Cx43-Dependent Manner
Authors: Kochanowski Paweł , Catapano Jessica , Pudełek Maciej , Wróbel Tomasz , Madeja Zbigniew , Ryszawy Damian , Czyż Jarosław
Published: April 2021

Glioblastoma multiforme (GBM) recurrences after temozolomide (TMZ) treatment result from the expansion of drug-resistant and potentially invasive GBM cells. This process is facilitated by O6-Methylguanine-DNA Methyltransferase (MGMT), which counteracts alkylating TMZ activity. We traced the expansion of invasive cell lineages under persistent chemotherapeutic stress in MGMTlow (U87) and MGMThigh (T98G) GBM populations to look into the mechanisms of TMZ-induced microevolution of GBM invasiveness. TMZ treatment induced short-term, pro-invasive phenotypic shifts of U87 cells, in the absence of Snail-1 activation. They were illustrated by a transient induction of their motility and followed by the hypertrophy and the signs of senescence in scarce U87 sub-populations that survived long-term TMZ stress. In turn, MGMThigh T98G cells reacted to the long-term TMZ treatment with the permanent induction of invasiveness. Ectopic Snail-1 down-regulation attenuated this effect, whereas its up-regulation augmented T98G invasiveness. MGMTlow and MGMThigh cells both reacted to the long-term TMZ stress with the induction of Cx43 expression. However, only in MGMThigh T98G populations, Cx43 was directly involved in the induction of invasiveness, as manifested by the induction of T98G invasiveness after ectopic Cx43 up-regulation and by the opposite effect after Cx43 down-regulation. Collectively, Snail-1/Cx43-dependent signaling participates in the long-term TMZ-induced microevolution of the invasive GBM front. High MGMT activity remains a prerequisite for this process, even though MGMT-related GBM chemoresistance is not necessary for its initiation.
A Balkan View on the Left Periphery: Modal and Discourse Particles
Authors: Roussou Anna
Published: April 2021

The present paper discusses two sets of so-called particles in the Balkan languages, arguing that the correspondences attested in the E-languages reveal abstract properties at the level of the I-language. The first set involves modal particles which participate in the analytic expressions of the “future” and the “subjunctive”. Future markers are construed as V-related elements externalizing a scope position of the verb, while the subjunctive markers take their features from the nominal set. The second set of data involves the discourse marker “haide” which is argued to externalize features associated with the force of the sentence and its anchoring to the discourse participants. In the case of modal particles, the languages under consideration retain their own lexica, while in the case of the discourse marker, they share the same lexical item (lexical borrowing). Analysis of these phenomena supports an articulated left periphery which also accounts for the similar distribution of the discourse marker “haide”. At the same time, the different externalizations leave room for further microparametric variation.
Effect of Electrodeposition Parameters on the Morphology, Topography and Corrosion Resistance of Epoxy Resin/Zinc Hybrid Coatings
Authors: Mureşan Alina Crina , Buruiană Daniela Laura , Istrate Gina Genoveva , Pintilie Ştefan Cătălin
Published: April 2021

The paper presents the morphology, topography and corrosion behavior of epoxy resin/zinc hybrid coatings obtained by electrodeposition from zinc sulphate electrolyte. The effect of current density and mean diameter size of polymer particles used for electrodeposition of the epoxy resin/zinc coatings on the morphology, topography and roughness of the surfaces were investigated by Scanning Electron Microscopy and Atomic Force Microscopy. The corrosion behavior of the hybrid coatings in 0.5 M sodium chloride solution was evaluated using electrochemical methods. For microbiological corrosion, the effect of sulphate reducing bacteria (SRB) on the surfaces was evaluated using epifluorescence microscopy. The surface roughness before and after bacteria attachment was evaluated using Atomic force microscopy. Polymer particles provide an influence in restricting the growth of zinc crystals as well as a catalytic role in nucleation sites increase. The results of electrochemical tests indicate a very good corrosion resistance of hybrid coatings comparing with zinc coatings. Epifluorescence images demonstrate that hybrid coating surfaces are slightly attacked by sulphate reducing bacteria.
To What Inanimate Matter Are We Most Closely Related and Does the Origin of Life Harbor Meaning?
Authors: Martin William F. , Nagies Falk S. P. , do Nascimento Vieira Andrey
Published: April 2021

The question concerning the meaning of life is important, but it immediately confronts the present authors with insurmountable obstacles from a philosophical standpoint, as it would require us to define not only what we hold to be life, but what we hold to be meaning in addition, requiring us to do both in a properly researched context. We unconditionally surrender to that challenge. Instead, we offer a vernacular, armchair approach to life’s origin and meaning, with some layman’s thoughts on the meaning of origins as viewed from the biologist’s standpoint. One can observe that biologists generally approach the concept of biological meaning in the context of evolution. This is the basis for the broad resonance behind Dobzhansky’s appraisal that “Nothing in biology makes sense except in the light of evolution”. Biologists try to understand living things in the historical context of how they arose, without giving much thought to the definition of what life or living things are, which for a biologist is usually not an interesting question in the practical context of daily dealings with organisms. Do humans generally understand life’s meaning in the context of history? If we consider the problem of life’s origin, the question of what constitutes a living thing becomes somewhat more acute for the biologist, though not more answerable, because it is inescapable that there was a time when there were no organisms on Earth, followed by a time when there were, the latter time having persisted in continuity to the present. This raises the question of where, in that transition, chemicals on Earth became alive, requiring, in turn, a set of premises for how life arose in order to conceptualize the problem in relation to organisms we know today, including ourselves, which brings us to the point of this paper: In the same way that cultural narratives for origins always start with a setting, scientific narratives for origins also always start with a setting, a place on Earth or elsewhere where we can imagine what happened for the sake of structuring both the problem and the narrative for its solution. This raises the question of whether scientific origins settings convey meaning to humans in that they suggest to us from what kind of place and what kinds of chemicals we are descended, that is, to which inanimate things we are most closely related.