bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Two-Level Fusion Feature for Mixed ECG Identity Recognition
Authors: Liu Xin , Si Yujuan , Yang Weiyi
Published: August 2021

In recent years, with the increasing standard of biometric identification, it is difficult to meet the requirements of data size and accuracy in practical application for training a single ECG (electrocardiogram) database. The paper aims to construct a recognition model for processing multi-source data and proposes a novel ECG identification system based on two-level fusion features. Firstly, the features of Hilbert transform and power spectrum are extracted from the segmented heartbeat data, then two features are combined into a set and normalized to obtain the elementary fusion feature. Secondly, PCANet (Principal Component Analysis Network) is used to extract the discriminative deep feature of signal, and MF (MaxFusion) algorithm is proposed to fuse and compress the two layers learning features. Finally, a linear support vector machine (SVM) is used to obtain labels of single feature classification and complete the individual identification. The recognition results of the proposed two-level fusion PCANet deep recognition network achieve more than 95% on ECG-ID, MIT-BIH, and PTB public databases. Most importantly, the recognition accuracy of the mixed database can reach 99.77%, which includes 426 individuals.
Smarter Robotic Sprayer System for Precision Agriculture
Authors: Baltazar André Rodrigues , Santos Filipe Neves dos , Moreira António Paulo , Valente António , Cunha José Boaventura
Published: August 2021

The automation of agricultural processes is expected to positively impact the environment by reducing waste and increasing food security, maximising resource use. Precision spraying is a method used to reduce the losses during pesticides application, reducing chemical residues in the soil. In this work, we developed a smart and novel electric sprayer that can be assembled on a robot. The sprayer has a crop perception system that calculates the leaf density based on a support vector machine (SVM) classifier using image histograms (local binary pattern (LBP), vegetation index, average, and hue). This density can then be used as a reference value to feed a controller that determines the air flow, the water rate, and the water density of the sprayer. This perception system was developed and tested with a created dataset available to the scientific community and represents a significant contribution. The results of the leaf density classifier show an accuracy score that varies between 80% and 85%. The conducted tests prove that the solution has the potential to increase the spraying accuracy and precision.
Comprehensive Design of DC Shipboard Power Systems for Pure Electric Propulsion Ship Based on Battery Energy Storage System
Authors: Kim Ye-Rin , Kim Jae-Myeong , Jung Jae-Jung , Kim So-Yeon , Choi Jae-Hak , Lee Hyun-Goo
Published: August 2021

With the strengthening of international environmental regulations, many studies on the integrated electric propulsion systems applicable to eco-friendly ship are being conducted. However, few studies have been performed to establish a guide line for the overall pure electric propulsion ship design. Therefore, this paper introduces the comprehensive design of DC shipboard power system for pure electric propulsion ship based on battery energy storage system (BESS). To design and configure the pure electric propulsion ship, 2 MW propulsion car ferry was assumed and adopted to be the target vessel in this paper. In order to design the overall system, a series of design processes, such as the decision of the ship operation profile, BESS capacity selection, configuration of the power conversion systems for propulsion, battery charging/discharging procedures, classification of system operation modes, and analysis of the efficiency, were considered. The proposed efficient design and analysis of the pure electric propulsion ship was qualitatively and quantitatively validated by MATLAB Simulink tool. The methodology presented in this paper can help design real ships before the system commissioning.
Fossil Energy in the Framework of Sustainable Development: Analysis of Prospects and Development of Forecast Scenarios
Authors: Zhukovskiy Yuriy Leonidovich , Batueva Daria Evgenievna , Buldysko Alexandra Dmitrievna , Gil Bernard , Starshaia Valeriia Vladimirovna
Published: August 2021

In the next 20 years, the fossil energy must become a guarantor of the sustainable development of the energy sector for future generations. Significant threats represent hurdles in this transition. This study identified current global trends in the energy sector and the prospects for the development of energy until 2035. The importance of risk assessment in scenario forecasting based on expert judgments was proven. Three contrasting scenarios, #StayHome, #StayAlone, and #StayEffective, for the development of fossil energy, all based on comprehensive analysis of global risks by expert survey and factor analysis, were developed. It was concluded that fossil energy is mandatory with integration of advanced technologies at every stage of the production of traditional energy and of renewable energy as an integral part of the modern energy sector. Based on the results of the study, nine ambitious programs for the development of sustainable energy are presented. They require the creation and the utilization of a single interactive digital platform adapted to this purpose. It is a passport mandatory for the flexible interaction of energy production, its transmission, and its consumption in the perspective of having a future sustainable, reliable, and secured energy sector.
Investigation of Control Characteristics for a Molten Salt Reactor Plant under Normal and Accident Conditions
Authors: Luo Run , Liu Chunyu , Macián-Juan Rafael
Published: August 2021

A molten salt reactor (MSR) has unique safety and economic advantages due to the liquid fluoride salt adopted as the reactor fuel and heat carrier fluid. The operation scheme and control strategy of the MSR plant are significantly different from those of traditional solid-fuel reactors because of the delayed neutron precursors drift with the liquid-fuel flow. In this paper, a simulation platform of the MSR plant is developed to study the control characteristics under normal and accident conditions. A nonlinear dynamic model of the whole system is built in the platform consisting of a liquid-fuel reactor with a graphite moderator, an intermediate heat exchanger and a steam generator. A new control strategy is presented based on a feed-forward and feedback combined scheme, a power control system and a steam temperature control system are designed to regulate load changes of the plant. Three different types of operation conditions are simulated with the control systems, including transients of normal load-follow operation, a reactivity insertion accident and a loss of flow accident. The simulation results show that the developed control system not only has a fast load-follow capability during normal operation, but also has a good control performance under accident conditions.
Star Wars? Space Weather and Electricity Market: Evidence from China
Authors: Wu Tong , You Zhe , Gong Mengqi , Cheng Jinhua
Published: August 2021

This paper aims to investigate the impact of space weather on China’s electricity market. Based on data products provided by NOAA and the National Energy Administration in China, this paper uses solar wind velocity as a solar weather indicator and the disturbance storm time index as a magnetospheric weather indicator to match monthly Chinese electricity market data over 10 years. Based on a VAR model, we found that (1) space weather increases the demand for electricity in China, and solar wind speed and the geomagnetic index increase the electricity consumption of the whole of Chinese society, as space weather mainly increases the electricity consumption of the secondary and industrial sectors. (2) The geomagnetic index significantly promotes power station revenue. (3) Space weather is associated with increased energy consumption. The geomagnetic index significantly increases the coal consumption rate of fossil power plants in China, but the solar wind speed has nothing to do with the coal consumption rate of fossil power plants.
Soft Switching of Non-Isolated Buck-Type Converter with Common-Ground Switch
Authors: Yau Yeu-Torng , Hwu Kuo-Ing , Shieh Jenn-Jong
Published: August 2021

A non-isolated buck converter, together with resonance and zero voltage transition to achieve zero voltage switching (ZVS) and zero current switching (ZCS), is presented herein to upgrade the conversion efficiency. In this circuit, the main switch and the auxiliary switch are connected to the common ground so as to make the two switches easily driven. Furthermore, these two switches take time division multiplexing operation. In addition, the pulse width modulation (PWM) control technique is utilized so as to render the output inductor and capacitor easily designed. In this paper, the theoretical derivation is first introduced, and secondly, some experimental results are provided to demonstrate the effectiveness of the proposed topology.
Development of an Adaptive Model Predictive Control for Platooning Safety in Battery Electric Vehicles
Authors: Capuano Antonio , Spano Matteo , Musa Alessia , Toscano Gianluca , Misul Daniela Anna
Published: August 2021

The recent and continuous improvement in the transportation field provides several different opportunities for enhancing safety and comfort in passenger vehicles. In this context, Adaptive Cruise Control (ACC) might provide additional benefits, including smoothness of the traffic flow and collision avoidance. In addition, Vehicle-to-Vehicle (V2V) communication may be exploited in the car-following model to obtain further improvements in safety and comfort by guaranteeing fast response to critical events. In this paper, firstly an Adaptive Model Predictive Control was developed for managing the Cooperative ACC scenario of two vehicles; as a second step, the safety analysis during a cut-in maneuver was performed, extending the platooning vehicles’ number to four. The effectiveness of the proposed methodology was assessed for in different driving scenarios such as diverse cruising speeds, steep accelerations, and aggressive decelerations. Moreover, the controller was validated by considering various speed profiles of the leader vehicle, including a real drive cycle obtained using a random drive cycle generator software. Results demonstrated that the proposed control strategy was capable of ensuring safety in virtually all test cases and quickly responding to unexpected cut-in maneuvers. Indeed, different scenarios have been tested, including acceleration and deceleration phases at high speeds where the control strategy successfully avoided any collision and stabilized the vehicle platoon approximately 20–30 s after the sudden cut-in. Concerning the comfort, it was demonstrated that improvements were possible in the aggressive drive cycle whereas different scenarios were found in the random cycle, depending on where the cut-in maneuver occurred.
Oxyfuel Combustion of a Model MSW—An Experimental Study
Authors: Becidan Michaël , Ditaranto Mario , Carlsson Per , Bakken Jørn , Olsen Maria N. P. , Stuen Johnny
Published: August 2021

The oxyfuel combustion of a model MSW (municipal solid waste) under various conditions was carried out in a lab-scale reactor. The aim was to study the behavior of MSW and identify challenges and opportunities associated with the development of this technology in the context of integration with CCS (carbon capture and storage). The experimental results show the effects of the oxidizer composition on the combustion process. Complete combustion can be attained under a variety of oxyfuel conditions, and the differences highlighted with O2/CO2 as an oxidizer compared with O2/N2 do not constitute showstoppers. MSW oxyfuel combustion hence offers a great potential for the combined (1) treatment of waste (contaminants’ destruction, volume, and weight reduction), (2) production of heat/power, and (3) CCS with negative CO2 emissions.
Evaluation of the Sectoral Energy Development Intensity in the Euro Area Countries
Authors: Ginevičius Romualdas , Bilan Yuriy , Kądzielawski Grzegorz , Novotny Miloslav , Kośmider Tomasz
Published: August 2021

National economic development largely depends on the development of the energy sector. Its condition is most commonly assessed based on the situation over the last year. An alternative approach, however, is to evaluate fluctuations in development that have occurred over a longer period. In this paper, both methodologies have been applied, in order to assess, based on the results, which of them is more accurate. The article hypothesizes that the second method is more accurate. To prove this empirically, values representing the energy development in various sectors (industrial, agricultural, transport, service and the other (miscellaneous) sectors) in various European countries over the 2009–2018 period were estimated. The development fluctuations that occurred during the period under consideration were evaluated according to two parameters—intensity and stability. The first parameter was taken to be the difference between the values representing energy development in a given sectors at the end and beginning of the period under consideration. The second parameter was taken as the aggregate change across consecutive time slots during which positive or negative fluctuations occurred. The value of energy development in a particular economic sector was estimated as the product of the latter coefficient and the development intensity indicator. Comparison of the results representing evaluation of energy development based on the methodology proposed, and the analysis of the situation in the last year for which data was available revealed that the results in both cases differed, with the values varying from 2% (for the transport sector) to 4.5% (for the agricultural sector). Taking into account the fact that the indicator representing energy development in particular economic sectors was estimated as a percentage of the total sectoral energy consumption, this difference was relatively significant (22.7 and 1.5% respectively). Thus, the findings suggest that application of the proposed methodology is relevant. The methodology provides a greater potential to adequately research issues related to national economic development.
Do People Understand and Observe the Effects of Climate Crisis on Forests? The Case Study of Cyprus
Authors: Miltiadou Milto , Antoniou Efrosyni , Theocharidis Christos , Danezis Chris
Published: August 2021

Recent reports stress the vulnerability of forest ecosystems in the European Union (EU), especially in the south. Cyprus is an island in the south of EU and the eastern of the Mediterranean Sea. While Cyprus’ vulnerability is stressed, Cyprus was included in the worst-performing countries regarding EU carbon emission’s targets of 2020. For mitigating climate change, Cyprus could benefit for tailored education and improved policy making. This study analyses the perceptions of the Cypriot residents about climate change and forest degradation aiming (1) to gain a better understanding of whether Cypriot residents understand its importance, (2) to understand if the general public is able to observe the changes noted in the literature, (3) to understand how perceptions are differentiated across different demographic categories, and (4) to derive correlations between demographic data and perceptions. This is a quantitative study; a questionnaire was used as a tool and the responses received were 416. It was highlighted that 65.62% of the participants stated that they noticed moderate to very much degradation of Cypriot coniferous forests. A potential degradation reason was written down by 150 people, of whom 31.33% referred to tree die-back, while many stated decreased soil moisture and difficulty in regeneration. All these reasons of degradation were either stated or suspected in the literature. Additionally, the demographic analysis showed that there may be an association between employability and beliefs/observations about climate change. The results of the research could be used for tailored education, further research, and promoting environmentally friendly policies. This will support Cyprus and other countries in reaching their Green Deal targets and, consequently, mitigate the severe effects of climate change.
A Novel Approach to Modelling Stand-Level Growth of an Even-Aged Forest Using a Volume Productivity Index with Application to New Zealand-Grown Coast Redwood
Authors: Kimberley Mark O. , Watt Michael S.
Published: August 2021

Empirical growth models are widely used to predict the growth and yield of plantation tree species, and the precise estimation of site quality is an important component of these models. The most commonly used proxy for site quality in growth models is Site Index (SI), which describes the mean height of dominant trees at a specified base age. Although SI is widely used, considerable research shows significant site-dependent variation in height for a given volume, with this latter variable more closely reflecting actual site productivity. Using a national dataset, this study develops and describes a stand-level growth and yield model for even-aged New Zealand-grown coast redwood (Sequoia sempervirens). We used a novel modelling approach that quantifies site quality using SI and a volume-based index termed the 300 Index, defined as the volume mean annual increment at age 30 years for a reference regime of 300 stems ha−1. The growth model includes a number of interrelated components. Mean top height is modelled from age and SI using a polymorphic Korf function. A modified anamorphic Korf function is used to describe tree quadratic mean diameter (Dq) as a function of age, stand density, SI and a diameter site index. As the Dq model includes stand density in its formulation, it can predict tree growth for different stand densities and thinning regimes. The mortality model is based on a simple attritional equation improved through incorporation of the Reineke stand density index to account for competition-induced mortality. Using these components, the model precisely estimates stand-level volume. The developed model will be of considerable value to growers for yield projection and regime evaluation. By more robustly describing the site effect, the growth model provides researchers with an improved framework for quantifying and understanding the causes of spatial and temporal variation in plantation productivity.
Should the Endoscopic Restrictions during COVID-19 Pandemic Remain Unchanged?
Authors: Bresky Emilio , Bresky Gustavo , Lancellotti Domingo , Madariaga Juan , Licuime Sebastian , Palma Paulette , Saez Fabian , Rojas Maria Jose , Seijas Luis
Published: August 2021

(Background) Endoscopic procedures are interventions that have been defined as carrying a high-risk of infection with COVID-19. Most endoscopy units restrict their activity based on pre-endoscopic diagnosis. (Objective) To determine the consequences of endoscopic restrictions as a result of the COVID-19 pandemic and their impact on digestive cancer diagnosis. (Design) A comparison of upper digestive endoscopies and colonoscopies with gastrointestinal cancers diagnosed between three endoscopic centers, two of which restricted their procedures and one that did not but performed the procedures under a strict protocol. (Setting) A retrospective analysis was performed collecting data between 15 March 2019 and 15 August 2020. Two-factor ANOVA and a Tukey’s a posteriori test were used as statistical tests. (Main outcome measures) There was variation in gastrointestinal cancer diagnosis between 2019 and 2020, considering the endoscopic procedures performed each year. (Result) There was a significant decrease in the total endoscopic procedures performed between 2019 and 2020 (p < 0.001), the result of reduced testing at the two centers (p < 0.001) with pre-endoscopic restrictions, which was not compensated for by a slight increase in procedures at the center without restrictions (p = 0.139). Regarding the total cancers diagnosed, while a significant decrease was observed for the two centers with pre-endoscopic restrictions (p = 0.007), a significant increase was registered in the center that maintained its endoscopic productivity (p < 0.001). After 851 procedures (537 upper digestive endoscopies and 314 colonoscopies) there was no evidence of COVID-19 infection in the endoscopic staff. (Conclusion) Endoscopic restrictions based on pre-endoscopic diagnosis should be reassessed in consideration of local pandemic situations, and a balance should be sought between COVID-19 infection risk and the detrimental delay of potential cancer diagnosis.
A Missense Variant in SLC39A4 in a Litter of Turkish Van Cats with Acrodermatitis Enteropathica
Authors: Kiener Sarah , Cikota Robert , Welle Monika , Jagannathan Vidhya , Åhman Susanne , Leeb Tosso
Published: August 2021

In a litter of Turkish Van cats, three out of six kittens developed severe signs of skin disease, diarrhea, and systemic signs of stunted growth at 6 weeks of age. Massive secondary infections of the skin lesions evolved. Histopathological examinations showed a mild to moderate hyperplastic epidermis, covered by a thick layer of laminar to compact, mostly parakeratotic keratin. The dermis was infiltrated with moderate amounts of lymphocytes and plasma cells. Due to the severity of the clinical signs, one affected kitten died and the other two had to be euthanized. We sequenced the genome of one affected kitten and compared the data to 54 control genomes. A search for private variants in the two candidate genes for the observed phenotype, MKLN1 and SLC39A4, revealed a single protein-changing variant, SLC39A4:c.1057G>C or p.Gly353Arg. The solute carrier family 39 member 4 gene (SLC39A4) encodes an intestinal zinc transporter required for the uptake of dietary zinc. The variant is predicted to change a highly conserved glycine residue within the first transmembrane domain, which most likely leads to a loss of function. The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 173 unrelated control cats. Together with the knowledge on the effects of SLC39A4 variants in other species, these data suggest SLC39A4:c.1057G>C as candidate causative genetic variant for the phenotype in the investigated kittens. In line with the human phenotype, we propose to designate this disease acrodermatitis enteropathica (AE).
Epigenetic Regulation of Inflammatory Responses in the Context of Physical Activity
Authors: Tarnowski Maciej , Kopytko Patrycja , Piotrowska Katarzyna
Published: August 2021

Epigenetic modifications occur in response to environmental changes and play a fundamental role in the regulation of gene expression. PA is found to elicit an inflammatory response, both from the innate and adaptive divisions of the immunological system. The inflammatory reaction is considered a vital trigger of epigenetic changes that in turn modulate inflammatory actions. The tissue responses to PA involve local and general changes. The epigenetic mechanisms involved include: DNA methylation, histone proteins modification and microRNA. All of them affect genetic expression in an inflammatory milieu in physical exercise depending on the magnitude of physiological stress experienced by the exerciser. PA may evoke acute or chronic biochemical and physiological responses and have a positive or negative immunomodulatory effect.
Characterizing HIV-1 Genetic Subtypes and Drug Resistance Mutations among Children, Adolescents and Pregnant Women in Sierra Leone
Authors: Yendewa George A. , Lakoh Sulaiman , Yendewa Sahr A. , Bangura Khadijah , Tabernilla Andrés , Patiño Lucia , Jiba Darlinda F. , Vandy Alren O. , Massaquoi Samuel P. , Osório Nuno S. , Deen Gibrilla F. , Sahr Foday , Salata Robert A. , Poveda Eva
Published: August 2021

Human immunodeficiency virus (HIV) drug resistance (HIVDR) is widespread in sub-Saharan Africa. Children and pregnant women are particularly vulnerable, and laboratory testing capacity remains limited. We, therefore, used a cross-sectional design and convenience sampling to characterize HIV subtypes and resistance-associated mutations (RAMs) in these groups in Sierra Leone. In total, 96 children (age 2–9 years, 100% ART-experienced), 47 adolescents (age 10–18 years, 100% ART-experienced), and 54 pregnant women (>18 years, 72% ART-experienced) were enrolled. Median treatment durations were 36, 84, and 3 months, respectively, while the sequencing success rates were 45%, 70%, and 59%, respectively, among children, adolescents, and pregnant women. Overall, the predominant HIV-1 subtype was CRF02_AG (87.9%, 95/108), with minority variants constituting 12%. Among children and adolescents, the most common RAMs were M184V (76.6%, n = 49/64), K103N (45.3%, n = 29/64), Y181C/V/I (28.1%, n = 18/64), T215F/Y (25.0%, n = 16/64), and V108I (18.8%, n = 12/64). Among pregnant women, the most frequent RAMs were K103N (20.6%, n = 7/34), M184V (11.8%, n = 4/34), Y181C/V/I (5.9%, n = 2/34), P225H (8.8%, n = 3/34), and K219N/E/Q/R (5.9%, n = 2/34). Protease and integrase inhibitor-RAMs were relatively few or absent. Based on the genotype susceptibility score distributions, 73%, 88%, and 14% of children, adolescents, and pregnant women, respectively, were not susceptible to all three drug components of the WHO preferred first-line regimens per 2018 guidelines. These findings suggest that routine HIVDR surveillance and access to better ART choices may improve treatment outcomes in Sierra Leone.
Genetic Markers of Differential Vulnerability to Sleep Loss in Adults
Authors: Casale Courtney , Goel Namni
Published: August 2021

In this review, we discuss reports of genotype-dependent interindividual differences in phenotypic neurobehavioral responses to total sleep deprivation or sleep restriction. We highlight the importance of using the candidate gene approach to further elucidate differential resilience and vulnerability to sleep deprivation in humans, although we acknowledge that other omics techniques and genome-wide association studies can also offer insights into biomarkers of such vulnerability. Specifically, we discuss polymorphisms in adenosinergic genes (ADA and ADORA2A), core circadian clock genes (BHLHE41/DEC2 and PER3), genes related to cognitive development and functioning (BDNF and COMT), dopaminergic genes (DRD2 and DAT), and immune and clearance genes (AQP4, DQB1*0602, and TNFα) as potential genetic indicators of differential vulnerability to deficits induced by sleep loss. Additionally, we review the efficacy of several countermeasures for the neurobehavioral impairments induced by sleep loss, including banking sleep, recovery sleep, caffeine, and naps. The discovery of reliable, novel genetic markers of differential vulnerability to sleep loss has critical implications for future research involving predictors, countermeasures, and treatments in the field of sleep and circadian science.
The NUNAtak Ice Thinning (NUNAIT) Calculator for Cosmonuclide Elevation Profiles
Authors: Rodés Ángel
Published: August 2021

Cosmogenic nuclides are widely used to constrain the landscape history of glaciated areas. At nunataks in continental polar regions with extremely arid conditions, cosmogenic nuclides are often the only method available to date the ice thinning history of the glacier. However, the amount of cosmogenic isotopes accumulated at the surface of nunataks depends not only on the length of time that rock has been exposed since the last deglaciation but also on the full history of the surface, including muon production under ice, exposure during previous interglacials, subaerial weathering rate, glacial erosion rate, and uplift rate of the nunatak. The NUNAtak Ice Thinning model (NUNAIT) simulates the cosmonuclide accumulation on vertical profiles, fitting the aforementioned parameters to a set of multi-isotope apparent ages from samples taken at different elevations over the ice-sheet surface. The NUNAIT calculator is an easy-to-use tool that constrains parameters that describe the geological history of a nunatak from a set of surface exposure ages.
Immune Cells Invade the Collateral Circulation during Human Stroke: Prospective Replication and Extension
Authors: Strinitz Marc , Pham Mirko , März Alexander G. , Feick Jörn , Weidner Franziska , Vogt Marius L. , Essig Fabian , Neugebauer Hermann , Stoll Guido , Schuhmann Michael K. , Kollikowski Alexander M.
Published: August 2021

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.
Exercise, but Not Metformin Prevents Loss of Muscle Function Due to Doxorubicin in Mice Using an In Situ Method
Authors: Mackay Amy D. , Marchant Erik D. , Louw Makensie , Thomson David M. , Hancock Chad R.
Published: August 2021

Though effective in treating various types of cancer, the chemotherapeutic doxorubicin (DOX) is associated with skeletal muscle wasting and fatigue. The purpose of this study was to assess muscle function in situ following DOX administration in mice. Furthermore, pre-treatments with exercise (EX) or metformin (MET) were used in an attempt to preserve muscle function following DOX. Mice were assigned to the following groups: control, DOX, DOX + EX, or DOX + MET, and were given a single injection of DOX (15 mg/kg) or saline 3 days prior to sacrifice. Preceding the DOX injection, DOX + EX mice performed 60 min/day of running for 5 days, while DOX + MET mice received 5 daily oral doses of 500 mg/kg MET. Gastrocnemius–plantaris–soleus complex function was assessed in situ via direct stimulation of the sciatic nerve. DOX treatment increased time to half-relaxation following contractions, indicating impaired recovery (p < 0.05). Interestingly, EX prevented any increase in half-relaxation time, while MET did not. An impaired relaxation rate was associated with a reduction in SERCA1 protein content (p = 0.07) and AMPK phosphorylation (p < 0.05). There were no differences between groups in force production or mitochondrial respiration. These results suggest that EX, but not MET may be an effective strategy for the prevention of muscle fatigue following DOX administration in mice.
Fourier Transform Infrared Microspectroscopy Combined with Principal Component Analysis and Artificial Neural Networks for the Study of the Effect of β-Hydroxy-β-Methylbutyrate (HMB) Supplementation on Articular Cartilage
Authors: Świetlicka Izabela , Muszyński Siemowit , Prein Carina , Clausen-Schaumann Hauke , Aszodi Attila , Arciszewski Marcin B. , Blicharski Tomasz , Gagoś Mariusz , Świetlicki Michał , Dobrowolski Piotr , Kras Katarzyna , Tomaszewska Ewa , Arczewska Marta
Published: August 2021

The potential of Fourier Transform infrared microspectroscopy (FTIR microspectroscopy) and multivariate analyses were applied for the classification of the frequency ranges responsible for the distribution changes of the main components of articular cartilage (AC) that occur during dietary β-hydroxy-β-methyl butyrate (HMB) supplementation. The FTIR imaging analysis of histological AC sections originating from 35-day old male piglets showed the change in the collagen and proteoglycan contents of the HMB-supplemented group compared to the control. The relative amount of collagen content in the superficial zone increased by more than 23% and in the middle zone by about 17%, while no changes in the deep zone were observed compared to the control group. Considering proteoglycans content, a significant increase was registered in the middle and deep zones, respectively; 62% and 52% compared to the control. AFM nanoindentation measurements collected from animals administered with HMB displayed an increase in AC tissue stiffness by detecting a higher value of Young’s modulus in all investigated AC zones. We demonstrated that principal component analysis and artificial neural networks could be trained with spectral information to distinguish AC histological sections and the group under study accurately. This work may support the use and effectiveness of FTIR imaging combined with multivariate analyses as a quantitative alternative to traditional collagenous tissue-related histology.
A Dansyl-Modified Sphingosine Kinase Inhibitor DPF-543 Enhanced De Novo Ceramide Generation
Authors: Shamshiddinova Maftuna , Gulyamov Shokhid , Kim Hee-Jung , Jung Seo-Hyeon , Baek Dong-Jae , Lee Yong-Moon
Published: August 2021

Sphingosine-1-phosphate (S1P) synthesized by sphingosine kinase (SPHK) is a signaling molecule, involved in cell proliferation, growth, differentiation, and survival. Indeed, a sharp increase of S1P is linked to a pathological outcome with inflammation, cancer metastasis, or angiogenesis, etc. In this regard, SPHK/S1P axis regulation has been a specific issue in the anticancer strategy to turn accumulated sphingosine (SPN) into cytotoxic ceramides (Cers). For these purposes, there have been numerous chemicals synthesized for SPHK inhibition. In this study, we investigated the comparative efficiency of dansylated PF-543 (DPF-543) on the Cers synthesis along with PF-543. DPF-543 deserved attention in strong cytotoxicity, due to the cytotoxic Cers accumulation by ceramide synthase (CerSs). DPF-543 exhibited dual actions on Cers synthesis by enhancing serine palmitoyltransferase (SPT) activity, and by inhibiting SPHKs, which eventually induced an unusual environment with a high amount of 3-ketosphinganine and sphinganine (SPA). SPA in turn was consumed to synthesize Cers via de novo pathway. Interestingly, PF-543 increased only the SPN level, but not for SPA. In addition, DPF-543 mildly activates acid sphingomyelinase (aSMase), which contributes a partial increase in Cers. Collectively, a dansyl-modified DPF-543 relatively enhanced Cers accumulation via de novo pathway which was not observed in PF-543. Our results demonstrated that the structural modification on SPHK inhibitors is still an attractive anticancer strategy by regulating sphingolipid metabolism.
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Authors: Sinsky Jakub , Pichlerova Karoline , Hanes Jozef
Published: August 2021

Tau protein plays a critical role in the assembly, stabilization, and modulation of microtubules, which are important for the normal function of neurons and the brain. In diseased conditions, several pathological modifications of tau protein manifest. These changes lead to tau protein aggregation and the formation of paired helical filaments (PHF) and neurofibrillary tangles (NFT), which are common hallmarks of Alzheimer’s disease and other tauopathies. The accumulation of PHFs and NFTs results in impairment of physiological functions, apoptosis, and neuronal loss, which is reflected as cognitive impairment, and in the late stages of the disease, leads to death. The causes of this pathological transformation of tau protein haven’t been fully understood yet. In both physiological and pathological conditions, tau interacts with several proteins which maintain their proper function or can participate in their pathological modifications. Interaction partners of tau protein and associated molecular pathways can either initiate and drive the tau pathology or can act neuroprotective, by reducing pathological tau proteins or inflammation. In this review, we focus on the tau as a multifunctional protein and its known interacting partners active in regulations of different processes and the roles of these proteins in Alzheimer’s disease and tauopathies.
The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review
Authors: Vahedi Parviz , Moghaddamshahabi Rana , Webster Thomas J. , Calikoglu Koyuncu Ayse Ceren , Ahmadian Elham , Khan Wasim S. , Jimale Mohamed Ali , Eftekhari Aziz
Published: August 2021

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.
Keratin 8/18 Regulate the Akt Signaling Pathway
Authors: Lim Younglan , Kim Sujin , Yoon Han-Na , Ku Nam-On
Published: August 2021

Keratin 8 and keratin 18 (K8/K18) are intermediate filament proteins that form the obligate heteropolymers in hepatocytes and protect the liver against toxins. The mechanisms of protection include the regulation of signaling pathway associated with cell survival. Previous studies show K8/K18 binding with Akt, which is a well-known protein kinase involved in the cell survival signaling pathway. However, the role of K8/K18 in the Akt signaling pathway is unclear. In this study, we found that K8/K18-Akt binding is downregulated by K8/K18 phosphorylation, specifically phosphorylation of K18 ser7/34/53 residues, whereas the binding is upregulated by K8 gly-62-cys mutation. K8/K18 expression in cultured cell system tends to enhance the stability of the Akt protein. A comparison of the Akt signaling pathway in a mouse system with liver damage shows that the pathway is downregulated in K18-null mice compared with nontransgenic mice. K18-null mice with Fas-induced liver damage show enhanced apoptosis combined with the downregulation of the Akt signaling pathway, i.e., lower phosphorylation levels of GSK3β and NFκB, which are the downstream signaling factors in the Akt signaling pathway, in K18-null mice compared with the control mice. Our study indicates that K8/K18 expression protects mice from liver damage by participating in enhancing the Akt signaling pathway.
Light-Inducible Spatio-Temporal Control of TLR4 and NF-κB-Gluc Reporter in Human Pancreatic Cell Line
Authors: Stierschneider Anna , Grünstäudl Petra , Colleselli Katrin , Atzler Josef , Klein Christian T. , Hundsberger Harald , Wiesner Christoph
Published: August 2021

Augmented Toll-like receptor 4 (TLR4) expression was found in nearly 70% of patients with pancreatic adenocarcinoma, which is correlated with increased tumorigenesis and progression. In this study, we engineered a new light-oxygen-voltage-sensing (LOV) domain-based optogenetic cell line (opto-TLR4 PANC-1) that enables time-resolved activation of the NF-κB and extracellular-signal regulated kinases (ERK)1/2 signalling pathway upon blue light-sensitive homodimerisation of the TLR4-LOV fusion protein. Continuous stimulation with light indicated strong p65 and ERK1/2 phosphorylation even after 24 h, whereas brief light exposure peaked at 8 h and reached the ground level 24 h post-illumination. The cell line further allows a voltage-dependent TLR4 activation, which can be continuously monitored, turned on by light or off in the dark. Using this cell line, we performed different phenotypic cell-based assays with 2D and 3D cultures, with the aim of controlling cellular activity with spatial and temporal precision. Light exposure enhanced cell attachment, the formation and extension of invadopodia, and cell migration in 3D spheroid cultures, but no significant changes in proliferation or viability could be detected. We conclude that the opto-TLR4 PANC-1 cell line is an ideal tool for investigating the underlying molecular mechanisms of TLR4, thereby providing strategies for new therapeutic options.
Caveolae-Mediated Endothelial Transcytosis across the Blood-Brain Barrier in Acute Ischemic Stroke
Authors: Zhou Min , Shi Samuel X. , Liu Ning , Jiang Yinghua , Karim Mardeen S. , Vodovoz Samuel J. , Wang Xiaoying , Zhang Boli , Dumont Aaron S.
Published: August 2021

Blood-brain barrier (BBB) disruption following ischemic stroke (IS) contributes to hemorrhagic transformation, brain edema, increased neural dysfunction, secondary injury, and mortality. Brain endothelial cells form a para and transcellular barrier to most blood-borne solutes via tight junctions (TJs) and rare transcytotic vesicles. The prevailing view attributes the destruction of TJs to the resulting BBB damage following IS. Recent studies define a stepwise impairment of the transcellular barrier followed by the paracellular barrier which accounts for the BBB leakage in IS. The increased endothelial transcytosis that has been proven to be caveolae-mediated, precedes and is independent of TJs disintegration. Thus, our understanding of post stroke BBB deficits needs to be revised. These recent findings could provide a conceptual basis for the development of alternative treatment strategies. Presently, our concept of how BBB endothelial transcytosis develops is incomplete, and treatment options remain limited. This review summarizes the cellular structure and biological classification of endothelial transcytosis at the BBB and reviews related molecular mechanisms. Meanwhile, relevant transcytosis-targeted therapeutic strategies for IS and research entry points are prospected.
Arterial Remodelling in Chronic Kidney Disease: Impact of Uraemic Toxins and New Pharmacological Approaches
Authors: Foudi Nabil , Palayer Maeva , Briet Marie , Garnier Anne-Sophie
Published: August 2021

Chronic kidney disease (CKD) is a major public health concern that affects around 10 percent of the world’s population. The severity of CKD is mainly due to the high prevalence of cardiovascular (CV) complications in this population. The aim of this review is to describe the arterial remodelling associated with CKD, to provide a quick overview of the mechanisms involved and to review the recent pharmacological approaches aimed at improving vascular health in CKD. CKD patients are exposed to metabolic and haemodynamic disorders that may affect the CV system. Large artery functional and geometric abnormalities have been well documented in CKD patients and are associated with an increase in arterial stiffness and a maladaptive remodelling. Uraemic toxins, such as indoxyl sulphate, p-cresyl sulphate, protein carbamylation and advanced glycation products, exert various effects on vascular smooth muscle cell functions. The low-grade inflammation associated with CKD may also affect arterial wall composition and remodelling. It is worth noting that the CV risk for CKD patients remains high despite the pharmacological control of traditional CV risk factors, suggesting the need for innovative therapeutic strategies. An interventional study targeting the NLRP3 inflammasome has provided some interesting preliminary results that need to be confirmed, especially in terms of safety.
Secundum Type Atrial Septal Defect in Patients with Trisomy 21—Therapeutic Strategies, Outcome, and Survival: A Nationwide Study of the German National Registry for Congenital Heart Defects
Authors: Lammers Astrid E. , Stegger Julia , Koerten Marc-André , Helm Paul C. , Bauer Ulrike M. , Baumgartner Helmut , Uebing Anselm S.
Published: August 2021

(1) Secundum type atrial septal defect (ASD II) is usually considered a relatively benign cardiac lesion amenable to elective closure at preschool age. Patients with trisomy 21 (T21), however, are known to have a higher susceptibility for pulmonary vascular disease (PVD). Therefore, T21 children may present with clinical symptoms earlier than those without associated anomalies. In addition, early PVD may even preclude closure in selected T21 patients. (2) We performed a retrospective analysis of the German National Register for Congenital Heart Defects including T21 patients with associated isolated ASD II. We report incidence, demographics, therapeutic strategy, outcome, and survival of this cohort. (3) Of 46,628 patients included in the registry, 1549 (3.3%) had T21. Of these, 156 (49.4% female) had an isolated ASD II. Fifty-four patients (34.6%) underwent closure at 6.4 ± 9.9 years of age. Over a cumulative follow-up (FU) of 1148 patient-years, (median 7.4 years), only one patient developed Eisenmenger syndrome and five patients died. Survival of T21 patients without PVD was not statistically different to age- and gender-matched controls from the normal population (p = 0.62), whereas children with uncorrected T21/ASD II (including patients with severe PVD, in whom ASD-closure was considered contraindicated) showed a significantly higher mortality. (4) The outcome of T21-patients with ASD II and without PVD is excellent. However, PVD, either precluding ASD-closure or development of progressive PVD after ASD-closure, is associated with significant mortality in this cohort. Thus T21 patients with ASD II who fulfill general criteria for closure and without PVD should be offered defect closure analogous to patients without T21.