bluuebunny/crossref_metadata_2025 huggingface dataset:
Porcelain Insulator Crack Location and Surface States Pattern Recognition Based on Hyperspectral Technology
Authors: Zhao Yiming , Yan Jing , Wang Yanxin , Jing Qianzhen , Liu Tingliang
Published: April 2021

A porcelain insulator is an important part to ensure that the insulation requirements of power equipment can be met. Under the influence of their structure, porcelain insulators are prone to mechanical damage and cracks, which will reduce their insulation performance. After a long-term operation, crack expansion will eventually lead to breakdown and safety hazards. Therefore, it is of great significance to detect insulator cracks to ensure the safe and reliable operation of a power grid. However, most traditional methods of insulator crack detection involve offline detection or contact measurement, which is not conducive to the online monitoring of equipment. Hyperspectral imaging technology is a noncontact detection technology containing three-dimensional (3D) spatial spectral information, whereby the data provide more information and the measuring method has a higher safety than electric detection methods. Therefore, a model of positioning and state classification of porcelain insulators based on hyperspectral technology is proposed. In this model, image data were used to extract edges to locate cracks, and spectral information was used to classify the surface states of porcelain insulators with EfficientNet. Lastly, crack extraction was realized, and the recognition accuracy of cracks and normal states was 96.9%. Through an analysis of the results, it is proven that the crack detection method of a porcelain insulator based on hyperspectral technology is an effective non-contact online monitoring approach, which has broad application prospects in the era of the Internet of Things with the rapid development of electric power.
Study of Dependence of Kinetic Freezeout Temperature on the Production Cross-Section of Particles in Various Centrality Intervals in Au–Au and Pb–Pb Collisions at High Energies
Authors: Waqas Muhammad , Peng Guang-Xiong
Published: April 2021

Transverse momentum spectra of π+, p, Λ, Ξ or Ξ¯+, Ω or Ω¯+ and deuteron (d) in different centrality intervals in nucleus–nucleus collisions at the center of mass energy are analyzed by the blast wave model with Boltzmann Gibbs statistics. We extracted the kinetic freezeout temperature, transverse flow velocity and kinetic freezeout volume from the transverse momentum spectra of the particles. It is observed that the non-strange and strange (multi-strange) particles freezeout separately due to different reaction cross-sections. While the freezeout volume and transverse flow velocity are mass dependent, they decrease with the resting mass of the particles. The present work reveals the scenario of a double kinetic freezeout in nucleus–nucleus collisions. Furthermore, the kinetic freezeout temperature and freezeout volume are larger in central collisions than peripheral collisions. However, the transverse flow velocity remains almost unchanged from central to peripheral collisions.
Towards Sustainable Crossbar Artificial Synapses with Zinc-Tin Oxide
Authors: Silva Carlos , Martins Jorge , Deuermeier Jonas , Pereira Maria Elias , Rovisco Ana , Barquinha Pedro , Goes João , Martins Rodrigo , Fortunato Elvira , Kiazadeh Asal
Published: April 2021

In this article, characterization of fully patterned zinc-tin oxide (ZTO)-based memristive devices with feature sizes as small as 25 µm2 is presented. The devices are patterned via lift-off with a platinum bottom contact and a gold-titanium top contact. An on/off ratio of more than two orders of magnitude is obtained without the need for electroforming processes. Set operation is a current controlled process, whereas the reset is voltage dependent. The temperature dependency of the electrical characteristics reveals a bulk-dominated conduction mechanism for high resistance states. However, the charge transport at low resistance state is consistent with Schottky emission. Synaptic properties such as potentiation and depression cycles, with progressive increases and decreases in the conductance value under 50 successive pulses, are shown. This validates the potential use of ZTO memristive devices for a sustainable and energy-efficient brain-inspired deep neural network computation.
Hourly Variation of Wind Speeds in the Philippines and Its Potential Impact on the Stability of the Power System
Authors: Lucas Kevin Ray Español , Sato Tomonori , Ohba Masamichi
Published: April 2021

Wind energy development has been limited by concerns associated to the varying features in wind speed which tends to destabilize the power system. This study aims to clarify the variability of winds within a day in the Philippines, specifically the hourly changes of onshore horizontal winds at 100-m hub-heights. A whole one-year experiment using the Weather Research and Forecasting model shows that onshore wind speeds decrease during the transitional hours between land breeze and sea breeze. The decreases in wind speed are most significant over coastal regions with high sloping topography. The extreme decreases in wind speed during morning hours, due to the natural processes, are found to often occur at the same time as the extreme electricity undersupply caused by the morning increase in energy demand. This result warns that the power system stability in the Philippines may become more sensitive to the variability of wind as the share of wind energy generation increases in the future. The findings of this study can contribute to promote sustainability in the operation of existing wind-reliant power systems and planning of future wind energy developments.
Design and Analysis of a Dual Airgap Radial Flux Permanent Magnet Vernier Machine with Yokeless Rotor
Authors: Siddiqi Mudassir Raza , Yazdan Tanveer , Im Jun-Hyuk , Humza Muhammad , Hur Jin
Published: April 2021

This paper presents a novel topology of dual airgap radial flux permanent magnet vernier machine (PMVM) in order to obtain a higher torque per magnet volume and similar average torque compared to a conventional PMVM machine. The proposed machine contains two stators and a sandwiched yokeless rotor. The yokeless rotor helps to reduce the magnet volume by providing an effective flux linkage in the stator windings. This effective flux linkage improved the average torque of the proposed machine. The competitiveness of the proposed vernier machine was validated using 2D finite element analysis under the same machine volume as that of conventional vernier machine. Moreover, cogging torque, torque ripples, torque density, losses, and efficiency performances also favored the proposed topology.
Development of AI-Based Diagnostic Model for the Prediction of Hydrate in Gas Pipeline
Authors: Seo Youngjin , Kim Byoungjun , Lee Joonwhoan , Lee Youngsoo
Published: April 2021

For the stable supply of oil and gas resources, industry is pushing for various attempts and technology development to produce not only existing land fields but also deep-sea, where production is difficult. The development of flow assurance technology is necessary because hydrate is aggregated in the pipeline and prevent stable production. This study established a system that enables hydrate diagnosis in the gas pipeline from a flow assurance perspective. Learning data were generated using an OLGA simulator, and temperature, pressure, and hydrate volume at each time step were generated. Stacked auto-encoder (SAE) was used as the AI model after analyzing training loss. Hyper-parameter matching and structure optimization were carried out using the greedy layer-wise technique. Through time-series forecast, we determined that AI diagnostic model enables depiction of the growth of hydrate volume. In addition, the average R-square for the maximum hydrate volume was 97%, and that for the formation location was calculated as 99%. This study confirmed that machine learning could be applied to the flow assurance area of gas pipelines and it can predict hydrate formation in real time.
The Use of the Fourier Series to Analyze the Shaping of Thermodynamic Processes in Heat Engines
Authors: Głogowski Michał , Kubiak Przemysław , Szufa Szymon , Piersa Piotr , Adrian Łukasz , Krukowski Mateusz
Published: April 2021

The article presents the application of the Fourier series to theoretical considerations on the method of maximum temperature control in thermodynamic cycles of internal combustion engines equipped with an additional independent kinematic system. The analysis assumes that the processes are zero-dimensional and the gases consumed in the engine cycles are perfect, simplifying the considerations for temperature control as a function of the two variables, pressure and volume, of which the volume as a geometric quantity can be completely controlled. In view of this fact, a predetermined temperature curve was assumed, ultimately reducing the considerations of specific volume changes, that is to say a kinematic system that could implement these changes. Moreover, in the analysis of volume changes, a cycle not used so far in the description of internal combustion engines was used. In the next step, the cycle was modified using the popular Vibe function, which was replaced in the theoretical cycle by two isochoric and isothermal transformations. Heat exchange was completely omitted in the considerations, in that it is of secondary importance, ultimately bringing the temperature function to the function of one variable, the angle of rotation of the crankshaft. Then, the kinematics was divided into the kinematics of the crank-piston system and the additional system, which was approximated with five words from the Fourier series, which in the technique correspond, for example, to the system of oscillators. At the end of the article we have explained one of the ways of actual technical implementation using a single nonlinear oscillator, the so-called ACC system equivalent to a few words from the mentioned Fourier series.
Physical Dimensions as a Design Objective in Heat Transfer Equipment: The Case of Plate and Fin Heat Exchangers
Authors: García-Castillo Jorge , Picón-Núñez Martín
Published: April 2021

To incorporate exchanger dimensions as a design objective in plate and fin heat exchangers, a variable that must be taken into consideration is the geometry of the finned surfaces to be used. In this work, a methodology to find the surface geometry that will produce the required heat transfer coefficient and pressure drop to achieve the design targets was developed. The geometry of secondary surfaces can be specified by the fin density, which represents the number of fins per unit length. All other geometrical features, as well as the thermo-hydraulic performance, can be derived from this parameter. This work showed the way finned surfaces are engineered employing generalised thermo-hydraulic correlations as a part of a design methodology. It also showed that there was a volume space referred to as volume design region (VDR) where heat duty, pressure drop, and dimensions could simultaneously be met. Such a volume design region was problem- and surface-specific; therefore, its limits were determined by the heat duty, the pressure drop, and the type of finned surface chosen in the design. The application of this methodology to a case study showed that a shell and tube heat exchanger of 227.4 m2, with the appropriate fin density using offset strip-fins, could be replaced by a plate and fin exchanger with any combination of height, width, and length in the ranges of 0–0.58 m, 0–0.58 m, and 0–3.59 m. The approach presented in this work indicated that heat exchanger dimensions could be fixed as a design objective, and they could effectively be achieved through surface design.
Analysis of Wind Turbine Aging through Operation Data Calibrated by LiDAR Measurement
Authors: Kim Hyun-Goo , Kim Jin-Young
Published: April 2021

This study analyzed the performance decline of wind turbine with age using the SCADA (Supervisory Control And Data Acquisition) data and the short-term in situ LiDAR (Light Detection and Ranging) measurements taken at the Shinan wind farm located on the coast of Bigeumdo Island in the southwestern sea of South Korea. Existing methods have generally attempted to estimate performance aging through long-term trend analysis of a normalized capacity factor in which wind speed variability is calibrated. However, this study proposes a new method using SCADA data for wind farms whose total operation period is short (less than a decade). That is, the trend of power output deficit between predicted and actual power generation was analyzed in order to estimate performance aging, wherein a theoretically predicted level of power generation was calculated by substituting a free stream wind speed projecting to a wind turbine into its power curve. To calibrate a distorted wind speed measurement in a nacelle anemometer caused by the wake effect resulting from the rotation of wind-turbine blades and the shape of the nacelle, the free stream wind speed was measured using LiDAR remote sensing as the reference data; and the nacelle transfer function, which converts nacelle wind speed into free stream wind speed, was derived. A four-year analysis of the Shinan wind farm showed that the rate of performance aging of the wind turbines was estimated to be −0.52%p/year.
The Role of Flexibility in Photovoltaic and Battery Optimal Sizing towards a Decarbonized Residential Sector
Authors: Dallapiccola Mattia , Barchi Grazia , Adami Jennifer , Moser David
Published: April 2021

The ambitious environmental goals set by the 2030 Climate Target Plan can be reached with a strong contribution coming from the residential sector and the exploitation of its flexibility, intended as the capacity of a building to shift its consumption to maximize the use of renewable energy. In the literature, the impact of flexibility has been mainly studied for the optimization of the control logic, assuming that the photovoltaic system and the electric storage have already been installed. Conversely, in this work, we adopt a different perspective that analyses the system from the designer point of view. Different scenarios with a variable degree of flexibility have been created and tested in a residential district considering various demand profiles (i.e., home appliances, heat pumps, and electric vehicles consumption). The profiles have been then used as input for an optimization tool that can design the optimal system according to a specific target function. Firstly, the system has been optimized according to economic indicators. However, results suggested that adopting only an economic perspective in the design phase could lead to results that are not in line with the European environmental targets. Thus, the system has been optimized also considering energy indicators to design a system that could give a relevant contribution to the energy transition of the residential sector. Results suggest that demand flexibility coupled with storage can boost the installation of photovoltaic systems due to the improved economic profitability and at the same time guarantee a relevant contribution to the decarbonization of the sector.
Cyber-Physical Systems Improving Building Energy Management: Digital Twin and Artificial Intelligence
Authors: Agostinelli Sofia , Cumo Fabrizio , Guidi Giambattista , Tomazzoli Claudio
Published: April 2021

The research explores the potential of digital-twin-based methods and approaches aimed at achieving an intelligent optimization and automation system for energy management of a residential district through the use of three-dimensional data model integrated with Internet of Things, artificial intelligence and machine learning. The case study is focused on Rinascimento III in Rome, an area consisting of 16 eight-floor buildings with 216 apartment units powered by 70% of self-renewable energy. The combined use of integrated dynamic analysis algorithms has allowed the evaluation of different scenarios of energy efficiency intervention aimed at achieving a virtuous energy management of the complex, keeping the actual internal comfort and climate conditions. Meanwhile, the objective is also to plan and deploy a cost-effective IT (information technology) infrastructure able to provide reliable data using edge-computing paradigm. Therefore, the developed methodology led to the evaluation of the effectiveness and efficiency of integrative systems for renewable energy production from solar energy necessary to raise the threshold of self-produced energy, meeting the nZEB (near zero energy buildings) requirements.
Investigating the Converter-Driven Stability of an Offshore HVDC System
Authors: Quester Matthias , Loku Fisnik , El Azzati Otmane , Noris Leonel , Yang Yongtao , Moser Albert
Published: April 2021

Offshore wind farms are increasingly built in the North Sea and the number of HVDC systems transmitting the wind power to shore increases as well. To connect offshore wind farms to adjacent AC transmission systems, onshore and offshore modular multilevel converters transform the transmitted power from AC to DC and vice versa. Additionally, modern wind farms mainly use wind turbines connected to the offshore point of common coupling via voltage source converters. However, converters and their control systems can cause unwanted interactions, referred to as converter-driven stability problems. The resulting instabilities can be predicted by applying an impedance-based analysis in the frequency domain. Considering that the converter models and system data are often confidential and cannot be exchanged in real systems, this paper proposes an enhanced impedance measurement method suitable for black-box applications to investigate the interactions. A frequency response analysis identifies coupling currents depending on the control system. The currents are subsequently added to the impedance models to achieve higher accuracy. The proposed method is applied to assess an offshore HVDC system’s converter-driven stability, using impedance measurements of laboratory converters and a wind turbine converter controller replica. The results show that the onshore modular multilevel converter interacts with AC grids of moderate short-circuit ratios. However, no interactions are identified between the offshore converter and the connected wind farm.
Fluid–Structure Interaction Simulation of a Coriolis Mass Flowmeter Using a Lattice Boltzmann Method
Authors: Haussmann Marc , Reinshaus Peter , Simonis Stephan , Nirschl Hermann , Krause Mathias J.
Published: April 2021

In this paper, we use a fluid–structure interaction (FSI) approach to simulate a Coriolis mass flowmeter (CMF). The fluid dynamics is calculated by the open-source framework OpenLB, based on the lattice Boltzmann method (LBM). For the structural dynamics we employ the open-source software Elmer, an implementation of the finite element method (FEM). A staggered coupling approach between the two software packages is presented. The finite element mesh is created by the mesh generator Gmsh to ensure a complete open source workflow. The Eigenmodes of the CMF, which are calculated by modal analysis, are compared with measurement data. Using the estimated excitation frequency, a fully coupled, partitioned, FSI simulation is applied to simulate the phase shift of the investigated CMF design. The calculated phase shift values are in good agreement to the measurement data and verify the suitability of the model to numerically describe the working principle of a CMF.
A New Approach for Dynamic Stochastic Fractal Search with Fuzzy Logic for Parameter Adaptation
Authors: Lagunes Marylu L. , Castillo Oscar , Valdez Fevrier , Soria Jose , Melin Patricia
Published: April 2021

Stochastic fractal search (SFS) is a novel method inspired by the process of stochastic growth in nature and the use of the fractal mathematical concept. Considering the chaotic stochastic diffusion property, an improved dynamic stochastic fractal search (DSFS) optimization algorithm is presented. The DSFS algorithm was tested with benchmark functions, such as the multimodal, hybrid, and composite functions, to evaluate the performance of the algorithm with dynamic parameter adaptation with type-1 and type-2 fuzzy inference models. The main contribution of the article is the utilization of fuzzy logic in the adaptation of the diffusion parameter in a dynamic fashion. This parameter is in charge of creating new fractal particles, and the diversity and iteration are the input information used in the fuzzy system to control the values of diffusion.
Knowledge of Antiretroviral Treatment and Associated Factors in HIV-Infected Patients
Authors: Van Nguyen Lam , Nguyen Thao N. P. , Thach Anh N. , Lam Anh N. , Lam Duc Q. , Duong Chu X. , Pham Suol T. , Nguyen Thao H. , Perwitasari Dyah A. , Taxis Katja , Nguyen Phuong M. , Nguyen Thang
Published: April 2021

This study aimed to assess the knowledge of antiretroviral (ARV) treatment and the associated factors in HIV-infected patients in Vietnam. We conducted a cross-sectional descriptive study of 350 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients being treated with ARV at outpatient clinics at Soc Trang, Vietnam, from June 2019 to December 2019. Using an interview questionnaire, patients who answered at least eight out of nine questions correctly, including some required questions, were considered to have a general knowledge of ARV treatment. Using multivariate logistic regression to identify factors associated with knowledge of ARV treatment, we found that 62% of HIV-infected patients had a general knowledge of ARV treatment, with a mean score of 8.2 (SD 1.4) out of 9 correct. A higher education level (p < 0.001); working away from home (p = 0.013); getting HIV transmitted by injecting drugs or from mother-to-child contact (p = 0.023); the presence of tension, anxiety, or stress (p = 0.005); self-reminding to take medication (p = 0.024); and a high self-evaluated adherence (p < 0.001) were found to be significantly associated with an adequate knowledge of ARV treatment. In conclusion, education programs for patients, as well as the quality of medical services and support, should be strengthened.
A Multilayer Perceptron Model for Stochastic Synthesis
Authors: Rozos Evangelos , Dimitriadis Panayiotis , Mazi Katerina , Koussis Antonis D.
Published: April 2021

Time series analysis is a major mathematical tool in hydrology, with the moving average being the most popular model type for this purpose due to its simplicity. During the last 20 years, various studies have focused on an important statistical characteristic, namely the long-term persistence and the simultaneous statistical consistency at all timescales, when different timescales are involved in the simulation. Though these issues have been successfully addressed by various researchers, the solutions that have been suggested are mathematically advanced, which poses a challenge regarding their adoption by practitioners. In this study, a multilayer perceptron network is used to obtain synthetic daily values of rainfall. In order to develop this model, first, an appropriate set of features was selected, and then, a custom cost function was crafted to preserve the important statistical properties in the synthetic time series. This approach was applied to two locations of different climatic conditions that have a long record of daily measurements (more than 100 years for the first and more than 40 years for the second). The results indicate that the suggested methodology is capable of preserving all important statistical characteristics. The advantage of this model is that, once it has been trained, it is straightforward to apply and can be modified easily to analyze other types of hydrologic time series.
Is a Mask That Covers the Mouth and Nose Free from Undesirable Side Effects in Everyday Use and Free of Potential Hazards?
Authors: Kisielinski Kai , Giboni Paul , Prescher Andreas , Klosterhalfen Bernd , Graessel David , Funken Stefan , Kempski Oliver , Hirsch Oliver
Published: April 2021

Many countries introduced the requirement to wear masks in public spaces for containing SARS-CoV-2 making it commonplace in 2020. Up until now, there has been no comprehensive investigation as to the adverse health effects masks can cause. The aim was to find, test, evaluate and compile scientifically proven related side effects of wearing masks. For a quantitative evaluation, 44 mostly experimental studies were referenced, and for a substantive evaluation, 65 publications were found. The literature revealed relevant adverse effects of masks in numerous disciplines. In this paper, we refer to the psychological and physical deterioration as well as multiple symptoms described because of their consistent, recurrent and uniform presentation from different disciplines as a Mask-Induced Exhaustion Syndrome (MIES). We objectified evaluation evidenced changes in respiratory physiology of mask wearers with significant correlation of O2 drop and fatigue (p < 0.05), a clustered co-occurrence of respiratory impairment and O2 drop (67%), N95 mask and CO2 rise (82%), N95 mask and O2 drop (72%), N95 mask and headache (60%), respiratory impairment and temperature rise (88%), but also temperature rise and moisture (100%) under the masks. Extended mask-wearing by the general population could lead to relevant effects and consequences in many medical fields.
Impact of COVID-19 Lockdown on Sun Exposure of UK Office Workers
Authors: Baczynska Katarzyna Anna , Rendell Rebecca J. , Khazova Marina
Published: April 2021

The impact of lockdown due to the COVID-19 pandemic in April–June 2020 on UV exposure of office workers was assessed using an online survey on time spent outdoors and environmental data for different locations in the UK. Without the need for commuting and with the flexibility of homeworking, weekday time spent outdoors was higher in the 2020 lockdown than in the same period in 2017. The weekday erythema effective radiant exposure was higher in 2020 due to an additional 45 min outdoors in the late afternoon that was not observed in 2017 and high UV levels due to extremely sunny weather in spring. The lockdown did not impact the frequency of time spent outdoors around midday, which was still governed by work commitments, and at the weekends, no difference between 2020 and 2017 was observed. In 2020, responders felt that time outdoors was very important for their health and well-being.
Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs
Authors: Wojtowicz Karolina , Sterzyńska Karolina , Świerczewska Monika , Nowicki Michał , Zabel Maciej , Januchowski Radosław
Published: April 2021

Our goal was to examine the anticancer effects of piperine against the resistant human ovarian cancer cells and to explore the molecular mechanisms responsible for its anticancer effects. Our study used drug-sensitive ovarian cancer cell line W1 and its sublines resistant to paclitaxel (PAC) and topotecan (TOP). We analyzed the cytotoxic effect of piperine and cytostatic drugs using an MTT assay. The impact of piperine on protein expression was determined by immunofluorescence and Western blot. We also examined its effect on cell proliferation and migration. We noticed a different level of piperine resistance between cell lines. Piperine increases the cytotoxic effect of PAC and TOP in drug-resistant cells. We observed an increase in PTPRK expression correlated with decreased pTYR level after piperine treatment and downregulation of P-gp and BCRP expression. We also noted a decrease in COL3A1 and TGFBI expression in investigated cell lines and increased COL3A1 expression in media from W1PR2 cells. The expression of Ki67 protein and cell proliferation rate decreased after piperine treatment. Piperine markedly inhibited W1TR cell migration. Piperine can be considered a potential anticancer agent that can increase chemotherapy effectiveness in cancer patients.
Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model
Authors: Friedmann Andrea , Baertel Andre , Schmitt Christine , Ludtka Christopher , Milosevic Javorina , Meisel Hans-Joerg , Goehre Felix , Schwan Stefan
Published: April 2021

Degenerated intervertebral discs (IVDs) were treated with autologous adipose-derived stem cells (ASC) loaded into an injectable collagen scaffold in a sheep model to investigate the implant’s therapeutic potential regarding the progression of degeneration of previously damaged discs. In this study, 18 merino sheep were subjected to a 3-step minimally invasive injury and treatment model, which consisted of surgically induced disc degeneration, treatment of IVDs with an ASC-loaded collagen hydrogel 6 weeks post-operatively, and assessment of the implant’s influence on degenerative tissue changes after 6 and 12 months of grazing. Autologous ASCs were extracted from subcutaneous adipose tissue and cultivated in vitro. At the end of the experiment, disc heights were determined by µ-CT measurements and morphological tissue changes were histologically examined.Histological investigations show that, after treatment with the ASC-loaded collagen hydrogel implant, degeneration-specific features were observed less frequently. Quantitative studies of the degree of degeneration did not demonstrate a significant influence on potential tissue regeneration with treatment. Regarding disc height analysis, at both 6 and 12 months after treatment with the ASC-loaded collagen hydrogel implant a stabilization of the disc height can be seen. A complete restoration of the intervertebral disc heights however could not be achieved.The reported injection procedure describes in a preclinical model a translational therapeutic approach for degenerative disc diseases based on adipose-derived stem cells in a collagen hydrogel scaffold. Further investigations are planned with the use of a different injectable scaffold material using the same test model.
Current Status of Gene Therapy Research in Polyglutamine Spinocerebellar Ataxias
Authors: Afonso-Reis Ricardo , Afonso Inês T. , Nóbrega Clévio
Published: April 2021

Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients.
Effect of Neuroprotective Magnesium Sulfate Treatment on Brain Transcription Response to Hypoxia Ischemia in Neonate Mice
Authors: Le Dieu-Lugon Bérénice , Dupré Nicolas , Derambure Céline , Janin François , Gonzalez Bruno J. , Marret Stéphane , Arabo Arnaud , Leroux Philippe
Published: April 2021

MgSO4 is widely used in the prevention of preterm neurological disabilities but its modes of action remain poorly established. We used a co-hybridization approach using the transcriptome in 5-day old mice treated with a single dose of MgSO4 (600 mg/kg), and/or exposed to hypoxia-ischemia (HI). The transcription of hundreds of genes was altered in all the groups. MgSO4 mainly produced repressions culminating 6 h after injection. Bio-statistical analysis revealed the repression of synaptogenesis and axonal development. The putative targets of MgSO4 were Mnk1 and Frm1. A behavioral study of adults did not detect lasting effects of neonatal MgSO4 and precluded NMDA-receptor-mediated side effects. The effects of MgSO4 plus HI exceeded the sum of the effects of separate treatments. MgSO4 prior to HI reduced inflammation and the innate immune response probably as a result of cytokine inhibition (Ccl2, Ifng, interleukins). Conversely, MgSO4 had little effect on HI-induced transcription by RNA-polymerase II. De novo MgSO4-HI affected mitochondrial function through the repression of genes of oxidative phosphorylation and many NAD-dehydrogenases. It also likely reduced protein translation by the repression of many ribosomal proteins, essentially located in synapses. All these effects appeared under the putative regulatory MgSO4 induction of the mTORC2 Rictor coding gene. Lasting effects through Sirt1 and Frm1 could account for this epigenetic footprint.
Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia—Molecular and Clinical Aspects
Authors: Dąbrowski Mikołaj , Kubaszewski Łukasz
Published: April 2021

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic disorders, and it is often asymptomatic and not a major issue for patients. The etiology of DISH is poorly understood, and known genetic factors indicate multiple signal pathways and multigene inheritance. In this review, we discuss the epidemiological, clinical, and etiological aspects of DISH with a special focus on dysphagia.
Predicting Pharmacokinetic Properties of Potential Anticancer Agents via Their Chromatographic Behavior on Different Reversed Phase Materials
Authors: Janicka Małgorzata , Mycka Anna , Sztanke Małgorzata , Sztanke Krzysztof
Published: April 2021

The Quantitative Structure-Activity Relationship (QSAR) methodology was used to predict biological properties, i.e., the blood–brain distribution (log BB), fraction unbounded in the brain (fu,brain), water-skin permeation (log Kp), binding to human plasma proteins (log Ka,HSA), and intestinal permeability (Caco-2), for three classes of fused azaisocytosine-containing congeners that were considered and tested as promising drug candidates. The compounds were characterized by lipophilic, structural, and electronic descriptors, i.e., chromatographic retention, topological polar surface area, polarizability, and molecular weight. Different reversed-phase liquid chromatography techniques were used to determine the chromatographic lipophilicity of the compounds that were tested, i.e., micellar liquid chromatography (MLC) with the ODS-2 column and polyoxyethylene lauryl ether (Brij 35) as the effluent component, an immobilized artificial membrane (IAM) chromatography with phosphatidylcholine column (IAM.PC.DD2) and chromatography with end-capped octadecylsilyl (ODS) column using aqueous solutions of acetonitrile as the mobile phases. Using multiple linear regression, we derived the statistically significant quantitative structure-activity relationships. All these QSAR equations were validated and were found to be very good. The investigations highlight the significance and possibilities of liquid chromatographic techniques with three different reversed-phase materials and QSARs methods in predicting the pharmacokinetic properties of our important organic compounds and reducing unethical animal testing.
Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression
Authors: Borczyk Malgorzata , Zieba Mateusz , Korostyński Michał , Piechota Marcin
Published: April 2021

The glucocorticoid receptor (GR, also known as NR3C1) coordinates molecular responses to stress. It is a potent transcription activator and repressor that influences hundreds of genes. Enhancers are non-coding DNA regions outside of the core promoters that increase transcriptional activity via long-distance interactions. Active GR binds to pre-existing enhancer sites and recruits further factors, including EP300, a known transcriptional coactivator. However, it is not known how the timing of GR-binding-induced enhancer remodeling relates to transcriptional changes. Here we analyze data from the ENCODE project that provides ChIP-Seq and RNA-Seq data at distinct time points after dexamethasone exposure of human A549 epithelial-like cell line. This study aimed to investigate the temporal interplay between GR binding, enhancer remodeling, and gene expression. By investigating a single distal GR-binding site for each differentially upregulated gene, we show that transcriptional changes follow GR binding, and that the largest enhancer remodeling coincides in time with the highest gene expression changes. A detailed analysis of the time course showed that for upregulated genes, enhancer activation persists after gene expression changes settle. Moreover, genes with the largest change in EP300 binding showed the highest expression dynamics before the peak of EP300 recruitment. Overall, our results show that enhancer remodeling may not directly be driving gene expression dynamics but rather be a consequence of expression activation.
Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far
Authors: McElwain Colm , McCarthy Fergus , McCarthy Cathal
Published: April 2021

Gestational diabetes mellitus (GDM) is an obstetric complication that affects approximately 5–10% of all pregnancies worldwide. GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy, and is characterized by exaggerated insulin resistance, a condition which is already pronounced in healthy pregnancies. Maternal hyperglycaemia ensues, instigating a ‘glucose stress’ response and concurrent systemic inflammation. Previous findings have proposed that both placental and visceral adipose tissue play a part in instigating and mediating this low-grade inflammatory response which involves altered infiltration, differentiation and activation of maternal innate and adaptive immune cells. The resulting maternal immune dysregulation is responsible for exacerbation of the condition and a further reduction in maternal insulin sensitivity. GDM pathology results in maternal and foetal adverse outcomes such as increased susceptibility to diabetes mellitus development and foetal neurological conditions. A clearer understanding of how these pathways originate and evolve will improve therapeutic targeting. In this review, we will explore the existing findings describing maternal immunological adaption in GDM in an attempt to highlight our current understanding of GDM-mediated immune dysregulation and identify areas where further research is required.
Targeting of Deregulated Wnt/β-Catenin Signaling by PRI-724 and LGK974 Inhibitors in Germ Cell Tumor Cell Lines
Authors: Schmidtova Silvia , Kalavska Katarina , Liskova Veronika , Plava Jana , Miklikova Svetlana , Kucerova Lucia , Matuskova Miroslava , Rojikova Lucia , Cierna Zuzana , Rogozea Adriana , Konig Heiko , Albany Costantine , Mego Michal , Chovanec Michal
Published: April 2021

The majority of patients with testicular germ cell tumors (GCTs) can be cured with cisplatin-based chemotherapy. However, for a subset of patients present with cisplatin-refractory disease, which confers a poor prognosis, the treatment options are limited. Novel therapies are therefore urgently needed to improve outcomes in this challenging patient population. It has previously been shown that Wnt/β-catenin signaling is active in GCTs suggesting that its inhibitors LGK974 and PRI-724 may show promise in the management of cisplatin-refractory GCTs. We herein investigated whether LGK-974 and PRI-724 provide a treatment effect in cisplatin-resistant GCT cell lines. Taking a genoproteomic approach and utilizing xenograft models we found the increased level of β-catenin in 2 of 4 cisplatin-resistant (CisR) cell lines (TCam-2 CisR and NCCIT CisR) and the decreased level of β-catenin and cyclin D1 in cisplatin-resistant NTERA-2 CisR cell line. While the effect of treatment with LGK974 was limited or none, the NTERA-2 CisR exhibited the increased sensitivity to PRI-724 in comparison with parental cell line. Furthermore, the pro-apoptotic effect of PRI-724 was documented in all cell lines. Our data strongly suggests that a Wnt/β-catenin signaling is altered in cisplatin-resistant GCT cell lines and the inhibition with PRI-724 is effective in NTERA-2 CisR cells. Further evaluation of Wnt/β-catenin pathway inhibition in GCTs is therefore warranted.
Ampelopsin Inhibits Cell Proliferation and Induces Apoptosis in HL60 and K562 Leukemia Cells by Downregulating AKT and NF-κB Signaling Pathways
Authors: Han Jang Mi , Kim Hong Lae , Jung Hye Jin
Published: April 2021

Leukemia is a type of blood cancer caused by the rapid proliferation of abnormal white blood cells. Currently, several treatment options, including chemotherapy, radiation therapy, and bone marrow transplantation, are used to treat leukemia, but the morbidity and mortality rates of patients with leukemia are still high. Therefore, there is still a need to develop more selective and less toxic drugs for the effective treatment of leukemia. Ampelopsin, also known as dihydromyricetin, is a plant-derived flavonoid that possesses multiple pharmacological functions, including antibacterial, anti-inflammatory, antioxidative, antiangiogenic, and anticancer activities. However, the anticancer effect and mechanism of action of ampelopsin in leukemia remain unclear. In this study, we evaluated the antileukemic effect of ampelopsin against acute promyelocytic HL60 and chronic myelogenous K562 leukemia cells. Ampelopsin significantly inhibited the proliferation of both leukemia cell lines at concentrations that did not affect normal cell viability. Ampelopsin induced cell cycle arrest at the sub-G1 phase in HL60 cells but the S phase in K562 cells. In addition, ampelopsin regulated the expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors differently in each leukemia cell. Ampelopsin also induced apoptosis in both leukemia cell lines through nuclear condensation, loss of mitochondrial membrane potential, increase in reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), and regulation of Bcl-2 family members. Furthermore, the antileukemic effect of ampelopsin was associated with the downregulation of AKT and NF-κB signaling pathways. Moreover, ampelopsin suppressed the expression levels of leukemia stemness markers, such as Oct4, Sox2, CD44, and CD133. Taken together, our findings suggest that ampelopsin may be an attractive chemotherapeutic agent against leukemia.
Signatures of Conical Intersection Dynamics in the Time-Resolved Photoelectron Spectrum of Furan: Theoretical Modeling with an Ensemble Density Functional Theory Method
Authors: Filatov Michael , Lee Seunghoon , Nakata Hiroya , Choi Cheol-Ho
Published: April 2021

The non-adiabatic dynamics of furan excited in the ππ* state (S2 in the Franck–Condon geometry) was studied using non-adiabatic molecular dynamics simulations in connection with an ensemble density functional method. The time-resolved photoelectron spectra were theoretically simulated in a wide range of electron binding energies that covered the valence as well as the core electrons. The dynamics of the decay (rise) of the photoelectron signal were compared with the excited-state population dynamics. It was observed that the photoelectron signal decay parameters at certain electron binding energies displayed a good correlation with the events occurring during the excited-state dynamics. Thus, the time profile of the photoelectron intensity of the K-shell electrons of oxygen (decay constant of 34 ± 3 fs) showed a reasonable correlation with the time of passage through conical intersections with the ground state (47 ± 2 fs). The ground-state recovery constant of the photoelectron signal (121 ± 30 fs) was in good agreement with the theoretically obtained excited-state lifetime (93 ± 9 fs), as well as with the experimentally estimated recovery time constant (ca. 110 fs). Hence, it is proposed to complement the traditional TRPES observations with the trXPS (or trNEXAFS) measurements to obtain more reliable estimates of the most mechanistically important events during the excited-state dynamics.
Circulating miRNAs Act as Diagnostic Biomarkers for Bladder Cancer in Urine
Authors: Lin Jen-Tai , Tsai Kuo-Wang
Published: April 2021

MicroRNAs (miRNAs) can be secreted into body fluids and have thus been reported as a new type of cancer biomarker. This study aimed to determine whether urinary miRNAs act as noninvasive biomarkers for diagnosing bladder cancer. Small RNA profiles from urine were generated for 10 patients with bladder cancer and 10 healthy controls by using next-generation sequencing. We identified 50 urinary miRNAs that were differentially expressed in bladder cancer compared with controls, comprising 44 upregulated and six downregulated miRNAs. Pathway enrichment analysis revealed that the biological role of these differentially expressed miRNAs might be involved in cancer-associated signaling pathways. Further analysis of the public database revealed that let-7b-5p, miR-149-5p, miR-146a-5p, miR-193a-5p, and miR-423-5p were significantly increased in bladder cancer compared with corresponding adjacent normal tissues. Furthermore, high miR-149-5p and miR-193a-5p expression was significantly correlated with poor overall survival in patients with bladder cancer. The qRT-PCR approach revealed that the expression levels of let-7b-5p, miR-149-5p, miR-146a-5p and miR-423-5p were significantly increased in the urine of patients with bladder cancer compared with those of controls. Although our results indicated that urinary miRNAs are promising biomarkers for diagnosing bladder cancer, this must be validated in larger cohorts in the future.