bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Urease, Elastase, and β-Glucuronidase Enzymatic Activity by Applying Aqueous Extracts of Opuntia oligacantha C.F. Först Acid Fruits: In Vitro Essay under Simulated Digestive Conditions
Authors: Medina-Pérez Gabriela , Peralta-Adauto Laura , Afanador-Barajas Laura , Fernández-Luqueño Fabián , Pérez-Soto Elizabeth , Campos-Montiel Rafael , Peláez-Acero Armando
Published: August 2021

Non-communicable diseases such as gastric inflammatory diseases and the hepatic pathologies are mainly related to bad lifestyle habits such as recurrent consumption of non-steroidal anti-inflammatory drugs (NSAIDs), excessive intake of alcohol, tobacco, steroids (high doses), alkaline agents, strong acid foods, and high-fat food, and Helicobacter pylori infections, among others. The fruit of Opuntia oligacantha C.F. Först var. Ulapa (xoconostle) is currently being studied due its nutritional and functional properties. The objective of the present study was to evaluate gastroprotective, anti-inflammatory, and hepatoprotective activities of different parts of xoconostle fruit by establishing in vitro simulated gastrointestinal conditions. Four treatments were established to test aqueous extracts (pericarp (P), mesocarp (M), endocarp (E) and whole fruit (W)). The quantified bioactive compounds were the total phenols, flavonoids, tannins, and betalains. The enzymatic assays were: urease, elastase, and β-glucuronidase. Significant differences (p < 0.05) of bioactive compounds content were measured in xoconostle extracts, the highest concentration was found in W (phenols 313 mg GAE/100 g, flavonoids 189 mg QE/100 g, tannins 71 mg CATE/100 g). The betalains content was higher in E; 17 mg/100 g significant differences were observed (p < 0.05) in the enzymatic inhibitions test (urease, elastase and β-glucuronidase), where W presented the highest inhibition activity (86%, 79%, and 84%), respectively. Bioactive compounds after in vitro gastrointestinal tests were maintained above 60% enzymatic inhibition activity.
XPS, SEM, DSC and Nanoindentation Characterization of Silver Nanoparticle-Coated Biopolymer Pellets
Authors: Motas Justina G. , Gorji Nima E. , Nedelcu Dumitru , Brabazon Dermot , Quadrini Fabrizio
Published: August 2021

The development of environmentally friendly materials has been the focus of many research groups in recent years due to increased harmful effects of plastics on the environment. Bio-based materials are considered a key solution from a sustainable manufacturing perspective. The nano-coating of biopolymer blends with silver nanoparticles is the subject of challenging research projects in line with the EU Directive on environment protection and sustainable manufacturing. Coating biopolymers with silver nanoparticles provides an antimicrobial and antiviral active surface. In this work, we develop silver nanoparticle-coated biopolymer Arboblend V2 Nature pellets. The main goal is to obtain a new material with antibacterial action obtained from the blending of a biopolymer pellets with silver nanoparticles through physical vapor deposition. The study is divided in three steps. The first step represents the silver nano-coating of the Arboblend V2 Nature and the characterization of the coated/raw pellets. The second step involves the injection molding of the silver nano-coated pellets and the characterization of the samples obtained. The last step regards the press molding of the coated pellets in order to obtain thin films, as well as their characterization. The PVD-sputtering technique is used to coat the pellets with silver nanoparticles. This process is especially optimized for coating raw materials with high water content and small-size pellets. The mechanical properties, surface chemical composition and the thermal properties of the both virgin and silver nanoparticle-coated biopolymer pellets are measured and analyzed for mechanical and thermal resistance of the nano-coating layer. Differential scanning calorimetry, scanning electron microscopy, X-ray photoemission spectroscopy and nanoindentation mechanical testing is performed. The calorimetry test detects no significant alteration of the biopolymer produced from the PVD process and confirms the optimized PVD process for nano-coating of the Arboblend V2 Nature pellets with a viable application in nano-silver–biopolymer composite products.
A Hazard Analysis Approach for the SOTIF in Intelligent Railway Driving Assistance Systems Using STPA and Complex Network
Authors: Zhang Shijie , Tang Tao , Liu Jintao
Published: August 2021

The Intelligent Railway Driving Assistance System (IRDAS) is a novel kind of onboard system that relies on its own situational awareness function to ensure the safety and efficiency of train driving. In such systems, the use of situational awareness brings about a new fault-free safety problem, i.e., the safety of the intended functionality (SOTIF). It is essential to analyze the SOTIF-related hazardous factors for ensuring a safe train operation. In this paper, a hazard analysis approach is proposed to capture and evaluate SOTIF-related hazardous factors of IRDAS. This approach consists of an extended STPA-based hazardous factor identification part and a complex network-based hazardous factor evaluation part. In the first part, an extended control structure of STPA is designed for the modeling of the situational awareness process, followed by a new classification of SOTIF-related causal scenarios to assist the identification of causal scenarios. In the second part, a modeling method for heterogeneous complex networks and some customized topological indexes are proposed to evaluate the hazardous factors identified in the STPA causal analysis. The outcomes of the approach can help develop targeted hazard control strategies. The proposed approach has been applied to a new IRDAS operating in Tsuen Wan Line of Hong Kong MTR. The result shows that the approach is effective for the analysis of hazardous factors and is helpful for the formulation of hazard control strategies.
Compliance of Distribution System Reactive Flows with Transmission System Requirements
Authors: Pediaditis Panagiotis , Sirviö Katja , Ziras Charalampos , Kauhaniemi Kimmo , Laaksonen Hannu , Hatziargyriou Nikos
Published: August 2021

Transmission system operators (TSOs) often set requirements to distribution system operators (DSOs) regarding the exchange of reactive power on the interface between the two parts of the system they operate, typically High Voltage and Medium Voltage. The presence of increasing amounts of Distributed Energy Resources (DERs) at the distribution networks complicates the problem, but provides control opportunities in order to keep the exchange within the prescribed limits. Typical DER control methods, such as constant cosϕ or Q/V functions, cannot adequately address these limits, while power electronics interfaced DERs provide to DSOs reactive power control capabilities for complying more effectively with TSO requirements. This paper proposes an optimisation method to provide power set-points to DERs in order to control the hourly reactive power exchanges with the transmission network. The method is tested via simulations using real data from the distribution substation at the Sundom Smart Grid, in Finland, using the operating guidelines imposed by the Finnish TSO. Results show the advantages of the proposed method compared to traditional methods for reactive power compensation from DERs. The application of more advanced Model Predictive Control techniques is further explored.
A Multivariate Randomized Controlled Experiment about the Effects of Mindfulness Priming on EEG Neurofeedback Self-Regulation Serious Games
Authors: da Costa Nuno M. C. , Bicho Estela , Ferreira Flora , Vilhena Estela , Dias Nuno S.
Published: August 2021

Neurofeedback training (NFT) is a technique often proposed to train brain activity SR with promising results. However, some criticism has been raised due to the lack of evaluation, reliability, and validation of its learning effects. The current work evaluates the hypothesis that SR learning may be improved by priming the subject before NFT with guided mindfulness meditation (MM). The proposed framework was tested in a two-way parallel-group randomized controlled intervention with a single session alpha NFT, in a simplistic serious game design. Sixty-two healthy naïve subjects, aged between 18 and 43 years, were divided into MM priming and no-priming groups. Although both the EG and CG successfully attained the up-regulation of alpha rhythms (F(1,59) = 20.67, p < 0.001, ηp2 = 0.26), the EG showed a significantly enhanced ability (t(29) = 4.38, p < 0.001) to control brain activity, compared to the CG (t(29) = 1.18, p > 0.1). Furthermore, EG superior performance on NFT seems to be explained by the subject’s lack of awareness at pre-intervention, less vigour at post-intervention, increased task engagement, and a relaxed non-judgemental attitude towards the NFT tasks. This study is a preliminary validation of the proposed assisted priming framework, advancing some implicit and explicit metrics about its efficacy on NFT performance, and a promising tool for improving naïve “users” self-regulation ability.
The Experimental Study of Innovative Methods Regarding the Removal of Sm(III)
Authors: Lobacheva Olga Leonidovna , Dzhevaga Natalia Vladimirovna
Published: August 2021

The modern development of the construction materials sector determines the use of rare earth metals (REM) for various purposes. In particular, REM are added as basic alloying elements into magnesium alloys to increase alloy durability and strength. The complex systematic study of structural components and REM interaction are the basis for the phase state monitoring of multicomponent oxide polyfunctional materials. In addition, on the preparatory stage, layers with specified construction material coatings are formed. The paper presents experimental and theoretical results of studies of adsorptive bubble methods in the systems containing Samarium cations and surfactants, namely sodium dodecyl sulphate (NaDS). To identify the process mechanisms and prediction of optimal conditions of metal cations’ removal and separation by extraction, flotation, and ion flotation methods, one should know the pH of metal hydroxo-complexes and pH of the hydrate formation. The possibility of lanthanide ions’ removal (by the example of Samarium ions) by the solvent sublation method with NaDS as a collector and isooctyl alcohol as an extractant was studied. From the obtained experimental data, it was clear that the Sm3+ removal in acidic mediums is practically non-existent. The results obtained in this paper are topical in the production of electrode coating components, welding fluxes, sorbents for nuclear wastewater burial, wastewater treatment, highly porous heat-insulating and fire-resistant materials, cement, and concrete with improved frost resistance.
Fault Diagnosis of Intelligent Production Line Based on Digital Twin and Improved Random Forest
Authors: Guo Kai , Wan Xiang , Liu Lilan , Gao Zenggui , Yang Muchen
Published: August 2021

Digital twin (DT) is a key technology for realizing the interconnection and intelligent operation of the physical world and the world of information and provides a new paradigm for fault diagnosis. Traditional machine learning algorithms require a balanced dataset. Training and testing sets must have the same distribution. Training a good generalization model is difficult in an actual production line operation process. Fault diagnosis technology based on the digital twin uses its ultrarealistic, multisystem, and high-precision characteristics to simulate fault data that are difficult to obtain in an actual production line to train a reliable fault diagnosis model. In this article, we first propose an improved random forest (IRF) algorithm, which reselects decision trees with high accuracy and large differences through hierarchical clustering and gives them weights. Digital twin technology is used to simulate a large number of balanced datasets to train the model, and the trained model can be transferred to a physical production line through transfer learning for fault diagnosis. Finally, the feasibility of our proposed algorithm is verified through a case study of an automobile rear axle assembly line, for which the accuracy of the proposed algorithm reaches 97.8%. The traditional machine learning plus digital twin fault diagnosis method proposed in this paper involves some generalization, and thus has practical value when extended to other fields.
Nonlinear Loads Compensation Using a Shunt Active Power Filter Controlled by Feedforward Neural Networks
Authors: Flores-Garrido Juan L. , Salmerón Patricio , Gómez-Galán Juan A.
Published: August 2021

The shunt active power filter (SAPF) is a widely used tool for compensation of disturbances in three-phase electric power systems. A high number of control methods have been successfully developed, including strategies based on artificial neural networks. However, the typical feedforward neural network, the multilayer perceptron, which has provided effective solutions to many nonlinear problems, has not yet been employed with satisfactory performance in the implementation of the SAPF control for obtaining the reference currents. In order to prove the capabilities of this simple neural topology, this work describes a suitable strategy of use, based on the accurate estimation of the Fourier coefficients corresponding to the fundamental harmonic of any distorted voltage or current. An effective training method has been developed, consisting of the use of many distorted patterns. The new generation procedure uses random combinations of multiple harmonics, including the possible nominal frequency deviations occurring in real power systems. The design of the generation of reference signals through computations based on the Fourier coefficients is presented. The objectives were the harmonic mitigation and power factor correction. Practical cases were tested through simulation and also by using an experimental platform, showing the feasibility of the proposal.
Cyber-Attack Scoring Model Based on the Offensive Cybersecurity Framework
Authors: Kim Kyounggon , Alfouzan Faisal Abdulaziz , Kim Huykang
Published: August 2021

Cyber-attacks have become commonplace in the world of the Internet. The nature of cyber-attacks is gradually changing. Early cyber-attacks were usually conducted by curious personal hackers who used simple techniques to hack homepages and steal personal information. Lately, cyber attackers have started using sophisticated cyber-attack techniques that enable them to retrieve national confidential information beyond the theft of personal information or defacing websites. These sophisticated and advanced cyber-attacks can disrupt the critical infrastructures of a nation. Much research regarding cyber-attacks has been conducted; however, there has been a lack of research related to measuring cyber-attacks from the perspective of offensive cybersecurity. This motivated us to propose a methodology for quantifying cyber-attacks such that they are measurable rather than abstract. For this purpose, we identified each element of offensive cybersecurity used in cyber-attacks. We also investigated the extent to which the detailed techniques identified in the offensive cyber-security framework were used, by analyzing cyber-attacks. Based on these investigations, the complexity and intensity of cyber-attacks can be measured and quantified. We evaluated advanced persistent threats (APT) and fileless cyber-attacks that occurred between 2010 and 2020 based on the methodology we developed. Based on our research methodology, we expect that researchers will be able to measure future cyber-attacks.
Machine Learning for the Identification of Hydration Mechanisms of Pharmaceutical-Grade Cellulose Polymers and Their Mixtures with Model Drugs
Authors: Talik Przemysław , Mendyk Aleksander
Published: August 2021

Differently bound water molecules confined in hydrated hydroxypropyl cellulose (HPC) type MF and their mixtures (1:1 w/w) with lowly soluble salicylic acid and highly soluble sodium salicylate were investigated by differential scanning calorimetry (DSC). The obtained ice-melting DSC curves of the HPC/H2O samples were deconvoluted into multiple components, using a specially developed curve decomposition tool. The ice-melting enthalpies of the individual deconvoluted components were used to estimate the amounts of water in three states in the HPC matrix: free water (FW), freezing bound water (FBW), and non-freezing water (NFW). A search for an optimal number of Gaussian functions was carried out among all available samples of data and was based on the analysis of the minimum fitting error vs. the number of Gaussians. Finally, three Gaussians accounting for three fractions of water were chosen for further analysis. The results of the calculations are discussed in detail and compared to previously obtained experimental DSC data. AI/ML tools assisted in theory elaboration and indirect validation of the hypothetical mechanism of the interaction of water with the HPC polymer.
Features of Ni-W Plating Film Obtained by the Jet-Flow System
Authors: Tsuruta Yuka , Umeda Yasushi , Honma Hideo , Takai Osamu , Tashiro Katsuhiko
Published: August 2021

Chromium plating has excellent corrosion resistance and is widely used in industry. However, it also has a high environmental load. As an alternative, electric Ni-W plating is attracting attention. However, it is not widely used because the stress is high and the film is prone to cracks. Furthermore, although it is necessary to thicken the film to improve the corrosion resistance, there are also problems that the current efficiency is low and the plating time is long. Therefore, we investigate a film with high corrosion resistance by using the jet-flow plating method that enables plating at a high current density. Our results show that the jet-flow plating enables plating of 50 µm, and high corrosion resistance is obtained by randomly generating fine cracks in the film at 20 A·dm−2. We also found that the stress changed depending on the current density and shape of the crack also changed.
Warming Trends of the Upper Troposphere in Taiwan Observed by Radiosonde and Surface Meteorological Stations at Various Altitudes
Authors: Hung Chih-wen , Shih Ming-Fu
Published: August 2021

In recent decades, a more prominent warming trend in the upper troposphere above the tropical western Pacific has been proposed in the literature derived from model simulations, satellite-borne observations, or reanalysis datasets. Rather than applying these “indirect” approaches, this study obtains surface-based and radiosonde observations in Taiwan in order to investigate long-term changes in temperature at different altitudes within the troposphere under the conditions of ongoing global warming. These surface-based observations indicate more pronounced warming in areas of high terrain, and the radiosondes reveal faster warming trends in the upper troposphere, with the maximum temperature increase between 400 hPa and 250 hPa. The upper-tropospheric warming becomes even more pronounced during boreal winter and spring; however, the intense warming does not carry over near the tropopause. Notable warming is also observed near the surface in Taipei, which may be related to the urban heat island effect caused by the rapid development of anthropic activities. Since Taiwan is located right on the edge of the tropics in the western Pacific, the upper-tropospheric warming, particularly between December and March, above the island should be contributed by the radiative and non-radiative processes, which were previously proposed by other studies.
Computer Simulations of Air Quality and Bio-Climatic Indices for the City of Sofia
Authors: Gadzhev Georgi , Ganev Kostadin
Published: August 2021

Air pollution is responsible for many adverse effects on human beings. Thermal discomfort, on the other hand, is able to overload the human body and eventually provoke health implications due to the heat imbalance. Methods: The aim of the presented work is to study the behavior of two bio-climatic indices and statistical characteristics of the air quality index for Sofia city—the capital of Bulgaria for the period 2008–2014. The study is based on the WRF-CMAQ model system simulations with a spatial resolution of 1 km. The air quality is estimated by the air quality index, taking into account the influence of different pollutants and the thermal conditions by two indices, respectively, for hot and cold weather. It was found that the recurrence of both the heat and cold index categories and of the air quality categories have heterogeneous space distribution and well manifested diurnal and seasonal variability. For all of the situations, only O3 and PM10 are the dominant pollutants—these which determine the AQI category. It was found that AQI1, AQI2, and AQI3, which fall in the “Low” band, have the highest recurrence during the different seasons, up to more than 70% in some places and situations. The recurrence of AQI10 (very high) is rather small—no more than 5% and concentrated in small areas, mostly in the city center. The Heat index of category “Danger” never appears, and the Heat index of category “Extreme caution” appears only in the spring and summer with the highest recurrence of less than 5% in the city center. For the Wind-chill index category, “Very High Risk” never appears, and the category “High Risk” appears with a frequency of about 1–2%. The above leads to the conclusion that both from a point of view of bioclimatic and air quality indices, the human health risks in the city of Sofia are not as high.
A Global Empirical Model of the Ion Temperature in the Ionosphere for the International Reference Ionosphere
Authors: Truhlík Vladimír , Bilitza Dieter , Kotov Dmytro , Shulha Maryna , Třísková Ludmila
Published: August 2021

This study presents a suggestion for improvement of the ion temperature (Ti) model in the International Reference Ionosphere (IRI). We have re-examined ion temperature data (primarily available from NASA’s Space Physics Data Facility (SPDF)from older satellites and combined them with newly available data from the Defense Meteorological Satellite Program (DMSP), the Communication Navigation Outage Forecasting System (C/NOFS), and from the recently launched Ionospheric Connection Explorer (ICON). We have compiled these data into a unified database comprising in total Ti data from 18 satellites. By comparisons with long term records of ion temperature from the three incoherent scatter radars (ISRs) (Jicamarca, Arecibo, and Millstone Hill), it was found that an intercalibration is needed to achieve consistency with the ISR data and among individual satellite data sets. This database with thus corrected data has been used for the development of a new global empirical model of Ti with inclusion of solar activity variation. This solar activity dependence is represented by an additive correction term to the Ti global pattern. Due to the limited data coverage at altitudes above 1000 km, the altitude range described by the model ranges from 350 km to 850 km covering only the region where generally Ti is higher than the neutral temperature (Tn) and lower than the electron temperature (Te). This approach is consistent with the current description of Ti in the IRI model. However, instead of one anchor point at 430 km altitude as in the current IRI, our approach includes anchor points at 350, 430, 600, and 850 km. At altitudes above 850 km Ti is merged using a gradient derived from the model at 600 and 850 km, with the electron temperature described by the IRI-2016/TBT-2012 option. Comparisons with the ISR data (Jicamarca, Arecibo, Millstone Hill, and Kharkiv) for high and low solar activity and equinox show that the proposed Ti model captures local time variation of Ti at different altitudes and latitudes better than the current IRI-2016 Ti model.
Analysis of the Precipitable Water Vapor Observation in Yunnan–Guizhou Plateau during the Convective Weather System in Summer
Authors: Hu Heng , Cao Yunchang , Shi Chuang , Lei Yong , Wen Hao , Liang Hong , Tu Manhong , Wan Xiaomin , Wang Haishen , Liang Jingshu , Zhao Panpan
Published: August 2021

The ERA5 reanalysis dataset of the European Center for Medium-Range Weather Forecasts (ECMWF) in the summers from 2015 to 2020 was used to compare and analyze the features of the precipitable water vapor (PWV) observed by six ground-based Global Navigation Satellite System (GNSS) meteorology (GNSS/MET) stations in the Yunnan–Guizhou Plateau. The correlation coefficients of the two datasets ranged between 0.804 and 0.878, the standard deviations ranged between 4.686 and 7.338 mm, and the monthly average deviations ranged between −4.153 and 9.459 mm, which increased with the altitude of the station. Matching the quality-controlled ground precipitation data with the PWV in time and space revealed that most precipitation occurred when the PWV was between 30 and 65 mm and roughly met the normal distribution. We used the vertical integral of divergence of moisture flux (∇p) and S-band Doppler radar networking products combined with the PWV to study the convergence and divergence process and the water vapor delivery conditions during the deep convective weather process from August 24 to 26, 2020, which can be used to analyze the real-time observation capability and continuity of PWV in small-scale and mesoscale weather processes. Furthermore, the 1 h precipitation and the cloud top temperature (ctt) data at the same site were used to demonstrate the effect of PWV on the transit of convective weather systems from different time–space scales.
Random Walk Analysis in a Reliability System under Constant Degradation and Random Shocks
Authors: Dshalalow Jewgeni H. , White Ryan T.
Published: August 2021

In this paper, we study a reliability system subject to occasional random shocks hitting an underlying device in accordance with a general marked point process with position dependent marking. In addition, the system ages according to a linear path that eventually fails even without any external shocks that accelerate the total failure. The approach for obtaining the distribution of the failure time falls into the area of random walk analysis. The results obtained are in closed form. A special case of a marked Poisson process with exponentially distributed marks is discussed that supports our claim of analytical tractability. The example is further confirmed by simulation. We also provide a classification of the literature pertaining to various reliability systems with degradation and shocks.
Polyploidy Improves Photosynthesis Regulation within the Ranunculus auricomus Complex (Ranunculaceae)
Authors: Ulum Fuad Bahrul , Hadacek Franz , Hörandl Elvira
Published: August 2021

Polyploidy has substantially contributed to successful plant evolution, and is often connected to a higher resilience to environmental stress. We test the hypothesis that polyploids tolerate light stress better than diploids. The Ranunculus auricomus complex comprises diploid (2x), tetraploid (4x), and hexaploid (6x) cytotypes, the former of which occur in shaded habitats and the latter more in open, sun-exposed habitats in Central Europe. In this study, we experimentally explored the effects of ploidy and photoperiod extension on the efficiency of photosystem II in the three cytotypes in climate growth chambers. Quantum yields and various coefficients that can be calculated from light curve, Kautsky curve, and fluorescent transient OJIP experiments provided support for the hypothesis that, in comparison to diploids, the improved regulation of excess light by more efficient photochemical and non-chemical quenching in polyploids might have facilitated the adaptation to unshaded habitats. We suggest how lower stress levels in reproductive tissues of polyploids might have favored asexual reproduction.
Comprehensive Utilization of Immature Honey Pomelo Fruit for the Production of Value-Added Compounds Using Novel Continuous Phase Transition Extraction Technology
Authors: Liu Guo , Hou Tao , Guo Shenglan , Lin Hongyu , Chen Meng , Miao Jianyin , Liu Xiaojuan , Huang Yahui , Cao Yong , Lan Yaqi , Song Mingyue
Published: August 2021

The immature honey pomelo fruit (IPF) is a huge agro-industrial by-product generated during pomelo planting. Although IPF is rich in nutrients, more than 95% of IPF is discarded annually, which causes resource waste and a serious environmental problem. Here, we report a novel continuous phase transition extraction technology (CPTE) to improve the comprehensive utilization of IPF by sequentially generating high value products and solve pollution problems related to their disposal. First, essential oil was successively extracted by CPTE at a yield of 1.12 ± 0.36%, in which 43 species were identified. Second, naringin extraction parameters were optimized using the response surface methodology (RSM), resulting in a maximum extraction rate of 99.47 ± 0.15%. Finally, pectin was extracted at a yield of 20.23 ± 0.66%, which is similar to the contents of commercial pectin. In conclusion, this study suggested that IPF was an excellent potential substrate for the production of value-added components by CPTE.
Gene Flow and Diversification in Himalopsyche martynovi Species Complex (Trichoptera: Rhyacophilidae) in the Hengduan Mountains
Authors: Deng Xi-Ling , Favre Adrien , Lemmon Emily Moriarty , Lemmon Alan R. , Pauls Steffen U.
Published: August 2021

The Hengduan Mountains are one of the most species-rich mountainous areas in the world. The origin and evolution of such a remarkable biodiversity are likely to be associated with geological or climatic dynamics, as well as taxon-specific biotic processes (e.g., hybridization, polyploidization, etc.). Here, we investigate the mechanisms fostering the diversification of the endemic Himalopsyche martynovi complex, a poorly known group of aquatic insects. We used multiple allelic datasets generated from 691 AHE loci to reconstruct species and RaxML phylogenetic trees. We selected the most reliable phylogenetic tree to perform network and gene flow analyses. The phylogenetic reconstructions and network analysis identified three clades, including H. epikur, H. martynovi sensu stricto and H. cf. martynovi. Himalopsyche martynovi sensu stricto and H. cf. martynovi present an intermediate morphology between H. epikur and H. viteceki, the closest known relative to the H. martynovi-complex. The gene flow analysis revealed extensive gene flow among these lineages. Our results suggest that H. viteceki and H. epikur are likely to have contributed to the evolution of H. martynovi sensu stricto and H. cf. martynovi via gene flow, and thus, our study provides insights in the diversification process of a lesser-known ecological group, and hints at the potential role of gene flow in the emergence of biological novelty in the Hengduan Mountains.
Anticoronavirus and Immunomodulatory Phenolic Compounds: Opportunities and Pharmacotherapeutic Perspectives
Authors: Dejani Naiara Naiana , Elshabrawy Hatem A. , Bezerra Filho Carlos da Silva Maia , de Sousa Damião Pergentino
Published: August 2021

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.
Role of Vitamin E and the Orexin System in Neuroprotection
Authors: La Torre Maria , Villano Ines , Monda Marcellino , Messina Antonietta , Cibelli Giuseppe , Valenzano Anna , Pisanelli Daniela , Panaro Maria , Tartaglia Nicola , Ambrosi Antonio , Carotenuto Marco , Monda Vincenzo , Messina Giovanni , Porro Chiara
Published: August 2021

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction between neurotransmitters and their specific receptors, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.
(Dys)Prosody in Parkinson’s Disease: Effects of Medication and Disease Duration on Intonation and Prosodic Phrasing
Authors: Frota Sónia , Cruz Marisa , Cardoso Rita , Guimarães Isabel , Ferreira Joaquim , Pinto Serge , Vigário Marina
Published: August 2021

The phonology of prosody has received little attention in studies of motor speech disorders. The present study investigates the phonology of intonation (nuclear contours) and speech chunking (prosodic phrasing) in Parkinson’s disease (PD) as a function of medication intake and duration of the disease. Following methods of the prosodic and intonational phonology frameworks, we examined the ability of 30 PD patients to use intonation categories and prosodic phrasing structures in ways similar to 20 healthy controls to convey similar meanings. Speech data from PD patients were collected before and after a dopaminomimetic drug intake and were phonologically analyzed in relation to nuclear contours and intonational phrasing. Besides medication, disease duration and the presence of motor fluctuations were also factors included in the analyses. Overall, PD patients showed a decreased ability to use nuclear contours and prosodic phrasing. Medication improved intonation regardless of disease duration but did not help with dysprosodic phrasing. In turn, disease duration and motor fluctuations affected phrasing patterns but had no impact on intonation. Our study demonstrated that the phonology of prosody is impaired in PD, and prosodic categories and structures may be differently affected, with implications for the understanding of PD neurophysiology and therapy.
Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes
Authors: Di Stazio Mariateresa , Bigoni Stefania , Iuso Nicola , Vuch Josef , Selvatici Rita , Ulivi Sheila , d’Adamo Pio Adamo
Published: August 2021

Background: Coffin–Lowry syndrome (CLS) is a syndromic form of X-linked intellectual disability, in which specific associated facial, hand, and skeletal abnormalities are diagnostic features. Methods: In the present study, an unreported missense genetic variant of the ribosomal S6 kinase 2 (RSK2) gene has been identified, by next-generation sequencing, in two related males with two different phenotypes of intellectual disability (ID) and peculiar facial dysmorphisms. We performed functional studies on this variant and another one, already reported in the literature, involving the same amino acid residue but, to date, without an efficient characterization. Results: Our study demonstrated that the two variants involving residue 189 significantly impaired its kinase activity. Conclusions: We detected a loss-of-function RSK2 mutation with loss in kinase activity in a three-generation family with an X-linked ID.
PER Gene Family Polymorphisms in Relation to Cluster Headache and Circadian Rhythm in Sweden
Authors: Jennysdotter Olofsgård Felicia , Ran Caroline , Fourier Carmen , Wirth Catalina , Sjöstrand Christina , Waldenlind Elisabet , Steinberg Anna , Belin Andrea Carmine
Published: August 2021

The trigeminal autonomic cephalalgia, cluster headache (CH), is one of the most painful disorders known to man. One of the disorder’s most striking features is the reported diurnal rhythmicity of the attacks. For a majority of patients, the headache attacks occur at approximately the same time every day. Genetic variants of genes involved in the circadian rhythm such as Period Circadian Regulator 1, 2, and 3 (PER1, 2 and 3) are hypothesized to have an effect on the rhythmicity of the attacks. Six PER1, 2 and 3 genetic markers; the indel rs57875989 and five single nucleotide polymorphisms (SNPs), rs2735611, rs2304672, rs934945, rs10462020, and rs228697, were genotyped, using TaqMan® or regular polymerase chain reaction (PCR), in a Swedish CH case control material. Logistic regression showed no association between CH and any of the six genetic variants; rs57875989, p = 0.523; rs2735611, p = 0.416; rs2304672, p = 0.732; rs934945, p = 0.907; rs10462020, p = 0.726; and rs228697, p = 0.717. Furthermore, no difference in allele frequency was found for patients reporting diurnal rhythmicity of attacks, nor were any of the variants linked to diurnal preference. The results of this study indicate no involvement of these PER genetic variants in CH or diurnal phenotype in Sweden.
Acute Regression in Down Syndrome
Authors: Handen Benjamin , Clare Isabel , Laymon Charles , Petersen Melissa , Zaman Shahid , O'Bryant Sid , Minhas Davneet , Tudorascu Dana , Brown Stephanie , Christian Bradley
Published: August 2021

Background: Acute regression has been reported in some individuals with Down syndrome (DS), typically occurring between the teenage years and mid to late 20s. Characterized by sudden, and often unexplained, reductions in language skills, functional living skills and reduced psychomotor activity, some individuals have been incorrectly diagnosed with Alzheimer’s disease (AD). Methods: This paper compares five individuals with DS who previously experienced acute regression with a matched group of 15 unaffected individuals with DS using a set of AD biomarkers. Results: While the sample was too small to conduct statistical analyses, findings suggest there are possible meaningful differences between the groups on proteomics biomarkers (e.g., NfL, total tau). Hippocampal, caudate and putamen volumes were slightly larger in the regression group, the opposite of what was hypothesized. A slightly lower amyloid load was found on the PET scans for the regression group, but no differences were noted on tau PET. Conclusions: Some proteomics biomarker findings suggest that individuals with DS who experience acute regression may be at increased risk for AD at an earlier age in comparison to unaffected adults with DS. However, due to the age of the group (mean 38 years), it may be too early to observe meaningful group differences on image-based biomarkers.
Vestibular Stimulation May Drive Multisensory Processing: Principles for Targeted Sensorimotor Therapy (TSMT)
Authors: Tele-Heri Brigitta , Dobos Karoly , Harsanyi Szilvia , Palinkas Judit , Fenyosi Fanni , Gesztelyi Rudolf , More Csaba E. , Zsuga Judit
Published: August 2021

At birth, the vestibular system is fully mature, whilst higher order sensory processing is yet to develop in the full-term neonate. The current paper lays out a theoretical framework to account for the role vestibular stimulation may have driving multisensory and sensorimotor integration. Accordingly, vestibular stimulation, by activating the parieto-insular vestibular cortex, and/or the posterior parietal cortex may provide the cortical input for multisensory neurons in the superior colliculus that is needed for multisensory processing. Furthermore, we propose that motor development, by inducing change of reference frames, may shape the receptive field of multisensory neurons. This, by leading to lack of spatial contingency between formally contingent stimuli, may cause degradation of prior motor responses. Additionally, we offer a testable hypothesis explaining the beneficial effect of sensory integration therapies regarding attentional processes. Key concepts of a sensorimotor integration therapy (e.g., targeted sensorimotor therapy (TSMT)) are also put into a neurological context. TSMT utilizes specific tools and instruments. It is administered in 8-weeks long successive treatment regimens, each gradually increasing vestibular and postural stimulation, so sensory-motor integration is facilitated, and muscle strength is increased. Empirically TSMT is indicated for various diseases. Theoretical foundations of this sensorimotor therapy are discussed.
A Contractor-Centric Construction Performance Model Using Non-Price Measures
Authors: Gunasekara Kasun , Perera Srinath , Hardie Mary , Jin Xiaohua
Published: August 2021

Selecting a better performing contractor at the procurement stage is crucial in achieving a successful outcome for a construction project. The construction industry lacks a systematic and purpose driven method to assess performance of contractors using objective metrics. There are many approaches to measuring construction performance, but most are complicated and have high dependency on data that is difficult to attain. This paper aims to create a model for evaluating construction contractors’ performance based on directly attributable measures that are quantitative and easy to gather. This makes such a model more attractive and easier to use. Initially, a detailed literature review revealed different categories of measures of performance (MoP) and corresponding critical measures of performance (CMoP). Through a series of Delphi-based expert forums, the set of measures were fine-tuned and shortlisted. Fuzzy analytic hierarchy process-based comparisons were then used for developing a contractors’ performance model to quantify their level of performance based on a limited set of organisation-specific and project-specific measures. The results indicate a shift from traditional measures and a higher preference towards non-price measures. The performance model can be further developed to systematically rank the prospective contractors at the procurement stage based on seven non-price measures.
Chromoanagenesis Landscape in 10,000 TCGA Patients
Authors: Rasnic Roni , Linial Michal
Published: August 2021

During the past decade, whole-genome sequencing of tumor biopsies and individuals with congenital disorders highlighted the phenomenon of chromoanagenesis, a single chaotic event of chromosomal rearrangement. Chromoanagenesis was shown to be frequent in many types of cancers, to occur in early stages of cancer development, and significantly impact the tumor’s nature. However, an in-depth, cancer-type dependent analysis has been somewhat incomplete due to the shortage in whole genome sequencing of cancerous samples. In this study, we extracted data from The Pan-Cancer Analysis of Whole Genome (PCAWG) and The Cancer Genome Atlas (TCGA) to construct and test a machine learning algorithm that can detect chromoanagenesis with high accuracy (86%). The algorithm was applied to ~10,000 unlabeled TCGA cancer patients. We utilize the chromoanagenesis assignment results, to analyze cancer-type specific chromoanagenesis characteristics in 20 TCGA cancer types. Our results unveil prominent genes affected in either chromoanagenesis or non-chromoanagenesis tumorigenesis. The analysis reveals a mutual exclusivity relationship between the genes impaired in chromoanagenesis versus non-chromoanagenesis cases. We offer the discovered characteristics as possible targets for cancer diagnostic and therapeutic purposes.
Selective Targeting of Class I Histone Deacetylases in a Model of Human Osteosarcoma
Authors: Torres Haydee M. , VanCleave Ashley M. , Vollmer Mykayla , Callahan Dakota L. , Smithback Austyn , Conn Josephine M. , Rodezno-Antunes Tania , Gao Zili , Cao Yuxia , Afeworki Yohannes , Tao Jianning
Published: August 2021

Dysregulation of histone deacetylases (HDACs) is associated with the pathogenesis of human osteosarcoma, which may present an epigenetic vulnerability as well as a therapeutic target. Domatinostat (4SC-202) is a next-generation class I HDAC inhibitor that is currently being used in clinical research for certain cancers, but its impact on human osteosarcoma has yet to be explored. In this study, we report that 4SC-202 inhibits osteosarcoma cell growth in vitro and in vivo. By analyzing cell function in vitro, we show that the anti-tumor effect of 4SC-202 involves the combined induction of cell-cycle arrest at the G2/M phase and apoptotic program, as well as a reduction in cell invasion and migration capabilities. We also found that 4SC-202 has little capacity to promote osteogenic differentiation. Remarkably, 4SC-202 revised the global transcriptome and induced distinct signatures of gene expression in vitro. Moreover, 4SC-202 decreased tumor growth of established human tumor xenografts in immunodeficient mice in vivo. We further reveal key targets regulated by 4SC-202 that contribute to tumor cell growth and survival, and canonical signaling pathways associated with progression and metastasis of osteosarcoma. Our study suggests that 4SC-202 may be exploited as a valuable drug to promote more effective treatment of patients with osteosarcoma and provide molecular insights into the mechanism of action of class I HDAC inhibitors.
Exploring the Interplay of Telomerase Reverse Transcriptase and β-Catenin in Hepatocellular Carcinoma
Authors: Kotiyal Srishti , Evason Kimberley Jane
Published: August 2021

Hepatocellular carcinoma (HCC) is one of the deadliest human cancers. Activating mutations in the telomerase reverse transcriptase (TERT) promoter (TERTp) and CTNNB1 gene encoding β-catenin are widespread in HCC (~50% and ~30%, respectively). TERTp mutations are predicted to increase TERT transcription and telomerase activity. This review focuses on exploring the role of TERT and β-catenin in HCC and the current findings regarding their interplay. TERT can have contradictory effects on tumorigenesis via both its canonical and non-canonical functions. As a critical regulator of proliferation and differentiation in progenitor and stem cells, activated β-catenin drives HCC; however, inhibiting endogenous β-catenin can also have pro-tumor effects. Clinical studies revealed a significant concordance between TERTp and CTNNB1 mutations in HCC. In stem cells, TERT acts as a co-factor in β-catenin transcriptional complexes driving the expression of WNT/β-catenin target genes, and β-catenin can bind to the TERTp to drive its transcription. A few studies have examined potential interactions between TERT and β-catenin in HCC in vivo, and their results suggest that the coexpression of these two genes promotes hepatocarcinogenesis. Further studies are required with vertebrate models to better understand how TERT and β-catenin influence hepatocarcinogenesis.