bluuebunny/crossref_metadata_2025 huggingface dataset:
Sesame Meal, Vitamin E and Selenium Influence Goats’ Antioxidant Status
Authors: Tsiplakou Eleni , Mitsiopoulou Christina , Karaiskou Chrysoula , Simoni Marica , Pappas Athanasios C. , Righi Federico , Sotirakoglou Kyriaki , Labrou Nikolaos E.
Published: March 2021

This study aimed to determine the impact of sesame meal, selenium (Se), and vitamin E (VitE) on goats’ oxidative status. Thirty mid-lactation crossbred goats were divided into five homogeneous groups, and were fed 1 kg of alfalfa hay and 1.2 kg of concentrates daily. The control group (C) received a basal diet. In the concentrates of the treated groups, 10% of the soybean meal was replaced by sesame meal and no extra VitE or Se (SM), or an extra 60 mg of VitE (SME), or 0.1 mg organic Se (SMSe), or their combination (60 mg VitE and 0,1 mg organic Se/kg of concentrate (SMESe). In the plasma of the goats, the dietary treatments did not affect glutathione reductase, glutathione peroxidase, glutathione transferase, catalase, superoxide dismutase activities, malondialdehyde (MDA) content, or the total antioxidant capacity. A reduction and a trend for lower protein carbonyls content was found in goats fed SM (p = 0.03) and SME (p = 0.06) compared to SMESe. In the milk, the lactoperoxidase activity decreased with SMSe and SMESe. A numerical decrease in the total antioxidant capacity and an increase in the MDA content in the milk of the SMESe group compared with the other treated groups was found. In mid-lactation goats, SM improves the oxidative status of both the organism and the milk.
Physalis peruviana-Derived Physapruin A (PHA) Inhibits Breast Cancer Cell Proliferation and Induces Oxidative-Stress-Mediated Apoptosis and DNA Damage
Authors: Yu Tzu-Jung , Cheng Yuan-Bin , Lin Li-Ching , Tsai Yi-Hong , Yao Bo-Yi , Tang Jen-Yang , Chang Fang-Rong , Yen Chia-Hung , Ou-Yang Fu , Chang Hsueh-Wei
Published: March 2021

Breast cancer expresses clinically heterogeneous characteristics and requires multipurpose drug development for curing the different tumor subtypes. Many withanolides have been isolated from Physalis species showing anticancer effects, but the anticancer function of physapruin A (PHA) has rarely been investigated. In this study, the anticancer properties of PHA in breast cancer cells were examined by concentration and time-course experiments. In terms of cellular ATP content, PHA inhibited the proliferation of three kinds of breast cancer cells: MCF7 (estrogen receptor (ER)+, progesterone receptor (PR)+/−, human epidermal growth factor receptor 2 (HER2)−), SKBR3 (ER−/PR−/HER2+), and MDA-MB-231 (triple-negative). Moreover, PHA induced G2/M arrest in MCF7 and MDA-MB-231 cells. In terms of flow cytometry, PHA induced the generation of reactive oxygen species (ROS), the generation of mitochondrial superoxide, mitochondrial membrane potential depletion, and γH2AX-detected DNA damage in breast cancer MCF7 and MDA-MB-231 cells, which were suppressed by the ROS inhibitor N-acetylcysteine (NAC). In terms of flow cytometry and Western blotting, PHA induced apoptotic expression (annexin V, and intrinsic and extrinsic apoptotic signaling), which was suppressed by NAC and an apoptosis inhibitor (Z-VAD-FMK), in breast cancer cells. Therefore, PHA is a potential anti-breast-cancer natural product that modulates the oxidative-stress response, cell-cycle disturbance, apoptosis, and γH2AX-detected DNA damage.
Life as a Vector of Dengue Virus: The Antioxidant Strategy of Mosquito Cells to Survive Viral Infection
Authors: Cheng Chih-Chieh , Sofiyatun Eny , Chen Wei-June , Wang Lian-Chen
Published: March 2021

Dengue fever is a mosquito-borne viral disease of increasing global importance. The disease has caused heavy burdens due to frequent outbreaks in tropical and subtropical areas of the world. The dengue virus (DENV) is generally transmitted between human hosts via the bite of a mosquito vector, primarily Aedes aegypti and Ae. albopictus as a minor species. It is known that the virus needs to alternately infect mosquito and human cells. DENV-induced cell death is relevant to the pathogenesis in humans as infected cells undergo apoptosis. In contrast, mosquito cells mostly survive the infection; this allows infected mosquitoes to remain healthy enough to serve as an efficient vector in nature. Overexpression of antioxidant genes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutaredoxin (Grx), thioredoxin (Trx), and protein disulfide isomerase (PDI) have been detected in DENV2-infected mosquito cells. Additional antioxidants, including GST, eukaryotic translation initiation factor 5A (eIF5a), and p53 isoform 2 (p53-2), and perhaps some others, are also involved in creating an intracellular environment suitable for cell replication and viral infection. Antiapoptotic effects involving inhibitor of apoptosis (IAP) upregulation and subsequent elevation of caspase-9 and caspase-3 activities also play crucial roles in the ability of mosquito cells to survive DENV infection. This article focused on the effects of intracellular responses in mosquito cells to infection primarily by DENVs. It may provide more information to better understand virus/cell interactions that can possibly elucidate the evolutionary pathway that led to the mosquito becoming a vector.
A Novel Binary QUasi-Affine TRansformation Evolutionary (QUATRE) Algorithm
Authors: Chu Shu-Chuan , Zhuang Zhongjie , Li Junbao , Pan Jeng-Shyang
Published: March 2021

QUasi-Affine TRansformation Evolutionary (QUATRE) algorithm generalized differential evolution (DE) algorithm to matrix form. QUATRE was originally designed for a continuous search space, but many practical applications are binary optimization problems. Therefore, we designed a novel binary version of QUATRE. The proposed binary algorithm is implemented using two different approaches. In the first approach, the new individuals produced by mutation and crossover operation are binarized. In the second approach, binarization is done after mutation, then cross operation with other individuals is performed. Transfer functions are critical to binarization, so four families of transfer functions are introduced for the proposed algorithm. Then, the analysis is performed and an improved transfer function is proposed. Furthermore, in order to balance exploration and exploitation, a new liner increment scale factor is proposed. Experiments on 23 benchmark functions show that the proposed two approaches are superior to state-of-the-art algorithms. Moreover, we applied it for dimensionality reduction of hyperspectral image (HSI) in order to test the ability of the proposed algorithm to solve practical problems. The experimental results on HSI imply that the proposed methods are better than Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA).
Health-Monitoring Methodology for High-Temperature Steam Pipes of Power Plants Using Real-Time Displacement Data
Authors: Choi Woosung , Han Jihoon
Published: March 2021

We developed a health-monitoring methodology for high-temperature steam pipes that estimated the life prediction of creep–fatigue interaction by directly measuring the displacement of hot parts. Three different methods (boiler code, design stress, and operating stress) were used to estimate the stress of the high-temperature pipe system. As a theoretical approach, the German boiler standard code calculates the stress according to the pipe shape, while design stress, which is also called allowable stress, was determined by a function of the operating temperature. The operating stress was immediately calculated using the surrogate model, with maximum displacement measured using the 3D displacement measurement system. To achieve the surrogate model, the stress was estimated by the pipe-stress analysis under the given displacements, and the surface-response model was developed to relate the stress and displacement. We showed that those methods are efficient methods to predict the stress and are applicable in health-monitoring methodology. Finally, the creep life and the low-cycle fatigue life were investigated using the Larson–Miller parameter equation, as well as the Smith, Hirschberg, and Manson equations. Our proposed monitoring system can be used to predict the fatigue and creep life of high-temperature steam pipes in real time, and we believe that the system can be applied to actual maintenance in thermal power plants.
Impact of Adenosine A2 Receptor Ligands on BCL2 Expression in Skeletal Muscle Cells
Authors: Haddad Mansour
Published: March 2021

Background: Adenosine plays the role of regulating cell differentiation, proliferation, and apoptosis in various kinds of cells through the B-cell lymphoma 2 (BCL2) pathway. Objectives: Since anti-apoptotic (BCL2) expression plays a role in controlling apoptosis in some cell lines, this study was designed to investigate whether adenosine analogue, NECA (non-selective adenosine receptors agonist), selective adenosine A2B receptor antagonist, PSB 603, and a selective adenosine A2A receptor agonist, CG21680, affect BCL2-gene expression in the skeletal muscle cells of rats. The purpose of this investigation was to test the hypothesis that CG21680 treatment would significantly intensify BCL2 gene expression in rat skeletal muscle. Methods: Flasks measuring 25 cm2 were employed in culturing the rat L6 skeletal muscle cells. After treating these differential cells, the relative mRNA expression level for the BCL2 gene, at varying conditions of treatment, was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: From the qRT-PCR analysis results, it was concluded that BCL2 expression was markedly amplified after selective adenosine A2A receptor agonist, CGS21680 (p < 0.01) treatment. More prospective validation for the adenosine receptors’ contribution in modulating apoptosis by NECA was delivered by the outcomes from the combined pre-treatment of the cells with NECA and PSB 603. These outcomes show that when starved skeletal muscle cells are treated with a combination of NECA and 100 nM PSB 603, there was a substantial decrease in comparison to either treatment used on its own. Conclusions: This study’s results showed, for the first time, an increase in BCL2 gene expression within skeletal muscle after CGS21680 treatment. Hence, the prospective escalation in BCL2 protein expression might have a protective role to play against apoptosis and avert damage to the skeletal muscle.
Uncertainties in the Seismic Assessment of Historical Masonry Buildings
Authors: Tomić Igor , Vanin Francesco , Beyer Katrin
Published: March 2021

Seismic assessments of historical masonry buildings are affected by several sources of epistemic uncertainty. These are mainly the material and the modelling parameters and the displacement capacity of the elements. Additional sources of uncertainty lie in the non-linear connections, such as wall-to-wall and floor-to-wall connections. Latin Hypercube Sampling was performed to create 400 sets of 11 material and modelling parameters. The proposed approach is applied to historical stone masonry buildings with timber floors, which are modelled by an equivalent frame approach using a newly developed macroelement accounting for both in-plane and out-of-plane failure. Each building is modelled first with out-of-plane behaviour enabled and non-linear connections, and then with out-of-plane behaviour disabled and rigid connections. For each model and set of parameters, incremental dynamic analyses are performed until building failure and seismic fragility curves derived. The key material and modelling parameters influencing the performance of the buildings are determined based on the peak ground acceleration at failure, type of failure and failure location. This study finds that the predicted PGA at failure and the failure mode and location is as sensitive to the properties of the non-linear connections as to the material and displacement capacity parameters, indicating that analyses must account for this uncertainty to accurately assess the in-plane and out-of-plane failure modes of historical masonry buildings. It also shows that modelling the out-of-plane behaviour produces a significant impact on the seismic fragility curves.
Deep Malaria Parasite Detection in Thin Blood Smear Microscopic Images
Authors: Maqsood Asma , Farid Muhammad Shahid , Khan Muhammad Hassan , Grzegorzek Marcin
Published: March 2021

Malaria is a disease activated by a type of microscopic parasite transmitted from infected female mosquito bites to humans. Malaria is a fatal disease that is endemic in many regions of the world. Quick diagnosis of this disease will be very valuable for patients, as traditional methods require tedious work for its detection. Recently, some automated methods have been proposed that exploit hand-crafted feature extraction techniques however, their accuracies are not reliable. Deep learning approaches modernize the world with their superior performance. Convolutional Neural Networks (CNN) are vastly scalable for image classification tasks that extract features through hidden layers of the model without any handcrafting. The detection of malaria-infected red blood cells from segmented microscopic blood images using convolutional neural networks can assist in quick diagnosis, and this will be useful for regions with fewer healthcare experts. The contributions of this paper are two-fold. First, we evaluate the performance of different existing deep learning models for efficient malaria detection. Second, we propose a customized CNN model that outperforms all observed deep learning models. It exploits the bilateral filtering and image augmentation techniques for highlighting features of red blood cells before training the model. Due to image augmentation techniques, the customized CNN model is generalized and avoids over-fitting. All experimental evaluations are performed on the benchmark NIH Malaria Dataset, and the results reveal that the proposed algorithm is 96.82% accurate in detecting malaria from the microscopic blood smears.
Transient Cold Flow Simulation of Fast-Fluidized Bed Air Reactor with Hematite as an Oxygen Carrier for Chemical Looping Combustion
Authors: Kumar Pulkit , Parwani Ajit K. , Gupta Dileep Kumar , Vitankar Vivek
Published: March 2021

Chemical looping combustion (CLC) is the most reliable carbon capture technology for curtailing CO2 insertion into the atmosphere. This paper presents the cold flow simulation results necessary to understand the hydrodynamic viability of the fast-fluidized bed air reactor. Hematite is selected as an oxygen carrier due to its easy availability and active nature during the reactions. The dense discrete phase model (DDPM) approach using the commercial software Ansys Fluent is applied in the simulation. An accurate and stable solution is achieved using the second-order upwind numerical scheme. A pressure difference of 150 kPa is obtained between the outlet and inlet of the selected air reactor, which is necessary for the movement of the particle. The stable circulating rate of hematite is achieved after 28 s of particle injection inside the air reactor. The results have been validated from the experimental results taken from the literature.
Calibrating a New Constitutive Tension Model to Extract a Simplified Nonlinear Sectional Analysis of Reinforced Concrete Beams
Authors: Abouelleil Alaaeldin , Rasheed Hayder A.
Published: March 2021

Nonlinear analysis of structural members is vital to understand the behavior and the response of reinforced concrete members. Even though most design procedures concentrate on the ultimate stage of response towards the end of the post-yielding zone as the decisive design criterion, the structural members usually function at the service load levels within the post-cracking zone. Therefore, cracking is a critical aspect of concrete behavior that affects the overall response of reinforced concrete beams. The initiation and the propagation of the cracks are affected directly by the tension and shear stresses in the beam. In flexural beams, the tensile stresses dominate the crack onset and its growth. Cracks in reinforced concrete flexural beams leave non-cracked regions in between the cracked sections. In order to apply a consistent analysis strategy, the smeared crack approach averages the behavior of these different cracked sections and uncracked in between regions to generate an accurate global response of the entire beam. This study presents a numerical constitutive tensile model that captures the complete tensile response of the reinforced concrete flexural member, in terms of averaged/smeared crack response. As a second step, this model was examined against a large pool of experimental data to validate its accuracy. Overall, the main objective of this study is to develop a representative constitutive tensile model for reinforced concrete flexural members and validate its accuracy against experimental results. The full nonlinear sectional response is analytically realized, based on the assumed trilinear moment–curvature response and the assumed trilinear moment–extreme fiber compressive strain response. This is considered as the secondary outcome of the present study.
Integrating Modelling of Maintenance Policies within a Stochastic Hybrid Automaton Framework of Dynamic Reliability
Authors: Arena Simone , Roda Irene , Chiacchio Ferdinando
Published: March 2021

The dependability assessment is a crucial activity for determining the availability, safety and maintainability of a system and establishing the best mitigation measures to prevent serious flaws and process interruptions. One of the most promising methodologies for the analysis of complex systems is Dynamic Reliability (also known as DPRA) with models that define explicitly the interactions between components and variables. Among the mathematical techniques of DPRA, Stochastic Hybrid Automaton (SHA) has been used to model systems characterized by continuous and discrete variables. Recently, a DPRA-oriented SHA modelling formalism, known as Stochastic Hybrid Fault Tree Automaton (SHyFTA), has been formalized together with a software library (SHyFTOO) that simplifies the resolution of complex models. At the state of the art, SHyFTOO allows analyzing the dependability of multistate repairable systems characterized by a reactive maintenance policy. Exploiting the flexibility of SHyFTA, this paper aims to extend the tools’ functionalities to other well-known maintenance policies. To achieve this goal, the main features of the preventive, risk-based and condition-based maintenance policies will be analyzed and used to design a software model to integrate into the SHyFTOO. Finally, a case study to test and compare the results of the different maintenance policies will be illustrated.
Shock Attenuation and Electromyographic Activity of Advanced and Novice Equestrian Riders’ Trunk
Authors: Elmeua González Marc , Šarabon Nejc
Published: March 2021

Low back pain (LBP) is a prevailing affliction among recreational and professional horse riders. It lowers performance and distracts from the development of the athlete. A lower incidence of LBP has been observed in the professional riding population despite higher training volumes. This paper aims to describe neuromuscular mechanisms through which advanced and novice riders attenuate the shockwave generated between the horse and rider. Six novice riders (age 24 ± 7 years), nine advanced riders (age 31 ± 5 years) and four horses (age 15 ± 3 years) took part in this study. Surface electromyographic activity of the riders’ trunk was recorded along with inertial data from the horses’ leg, saddle and vertebrae of the riders at walk, trot and canter. Analyses of variances revealed a superior shock attenuating ability of the advanced group (F (1,38) > 5.023, p < 0.03) as well as a higher overall muscle tone (F (1,488) > 9.80, p < 0.02). Cross correlation analyses between shock attenuation and electromyographic activity showed that groups differ mostly in timing rather than the intensity of muscle activation. This finding is of great interest for equestrian athletes and coaches, as it points to a greater importance of training muscular anticipation within the trunk stabilizers rather than overall muscle activation.
A Survey of Methods and Technologies for Congestion Estimation Based on Multisource Data Fusion
Authors: Cvetek Dominik , Muštra Mario , Jelušić Niko , Tišljarić Leo
Published: March 2021

Traffic congestion occurs when traffic demand is greater than the available network capacity. It is characterized by lower vehicle speeds, increased travel times, arrival unreliability, and longer vehicular queueing. Congestion can also impose a negative impact on the society by decreasing the quality of life with increased pollution, especially in urban areas. To mitigate the congestion problem, traffic engineers and scientists need quality, comprehensive, and accurate data to estimate the state of traffic flow. Various types of data collection technologies have different advantages and disadvantages as well as data characteristics, such as accuracy, sampling frequency, and geospatial coverage. Multisource data fusion increases the accuracy and provides a comprehensive estimation of the performance of traffic flow on a road network. This paper presents a literature overview related to the estimation of congestion and prediction based on the data collected from multiple sources. An overview of data fusion methods and congestion indicators used in the literature for traffic state and congestion estimation is given. Results of these methods are analyzed, and a disseminative analysis of the advantages and disadvantages of surveyed methods is presented.
Adaptive Optimal Robust Control for Uncertain Nonlinear Systems Using Neural Network Approximation in Policy Iteration
Authors: Xu Dengguo , Wang Qinglin , Li Yuan
Published: March 2021

In this study, based on the policy iteration (PI) in reinforcement learning (RL), an optimal adaptive control approach is established to solve robust control problems of nonlinear systems with internal and input uncertainties. First, the robust control is converted into solving an optimal control containing a nominal or auxiliary system with a predefined performance index. It is demonstrated that the optimal control law enables the considered system globally asymptotically stable for all admissible uncertainties. Second, based on the Bellman optimality principle, the online PI algorithms are proposed to calculate robust controllers for the matched and the mismatched uncertain systems. The approximate structure of the robust control law is obtained by approximating the optimal cost function with neural network in PI algorithms. Finally, in order to illustrate the availability of the proposed algorithm and theoretical results, some numerical examples are provided.
Prototype of Augmented Reality Technology for Orthodontic Bracket Positioning: An In Vivo Study
Authors: Lo Yu-Cheng , Chen Guan-An , Liu Yin-Chun , Chen Yuan-Hou , Hsu Jui-Ting , Yu Jian-Hong
Published: March 2021

To improve the accuracy of bracket placement in vivo, a protocol and device were introduced, which consisted of operative procedures for accurate control, a computer-aided design, and an augmented reality–assisted bracket navigation system. The present study evaluated the accuracy of this protocol. Methods: Thirty-one incisor teeth were tested from four participators. The teeth were bonded by novice and expert orthodontists. Compared with the control group by Boone gauge and the experiment group by augmented reality-assisted bracket navigation system, our study used for brackets measurement. To evaluate the accuracy, deviations of positions for bracket placement were measured. Results: The augmented reality-assisted bracket navigation system and control group were used in the same 31 cases. The priority of bonding brackets between control group or experiment group was decided by tossing coins, and then the teeth were debonded and the other technique was used. The medium vertical (incisogingival) position deviation in the control and AR groups by the novice orthodontist was 0.90 ± 0.06 mm and 0.51 ± 0.24 mm, respectively (p < 0.05), and by the expert orthodontist was 0.40 ± 0.29 mm and 0.29 ± 0.08 mm, respectively (p < 0.05). No significant changes in the horizontal position deviation were noted regardless of the orthodontist experience or use of the augmented reality–assisted bracket navigation system. Conclusion: The augmented reality–assisted bracket navigation system increased the accuracy rate by the expert orthodontist in the incisogingival direction and helped the novice orthodontist guide the bracket position within an acceptable clinical error of approximately 0.5 mm.
Nutritional Values of Onion Bulbs with Some Essential Structural Parameters for Packaging Process
Authors: Sami Rokayya , Elhakem Abeer , Alharbi Mona , Benajiba Nada , Almatrafi Manal , Helal Mahmoud
Published: March 2021

Onions belong to the Allium genus that has been frequently used for human diet and the traditional medication due to the bioactive compounds. The main nutritional values, vitamins, and amino acid compositions of onion bulbs (Yellow, Red, Green, Leek, and Baby onions) with some essential structural parameters for the packaging process were investigated. Physical and structural parameters with frictions were applied for the packaging process. The results reported that moisture content was the main component of onion bulbs (88.65%). Besides, they were rich in proteins (9.22–13.21 g/100 g infresh weight) (FW). Results reported that Red and Yellow varieties established the largest vitamin C and carotenoids contents (45.07 mg/100 g−1 FW) and (1.44 µg/mL FW), respectively. The major amino acid was arginine which was highly found in Green variety (17.02 mg/g FW) and a relatively high amount of glutamic and aspartic acids as (9.88–14.89 mg/g FW) and (4.93–10.55 mg/g FW), respectively. Yellow variety established the largest width, thickness, surface area, aspect ratio, and sphericity. The highest static and kinetic frictions were established on steel (0.14–0.52) and (0.75–0.96), respectively. This study presents the nutritional evidence of onion varieties for the human diet besides the horticultural processing for packaging quality improvement.
The Less Known Cyclins—Uncovered
Authors: Żuryń Agnieszka , Opacka Aleksandra , Krajewski Adrian , Zielińska Wioletta , Grzanka Alina
Published: March 2021

Cyclins belong to a group of proteins that are cyclically produced and destructed in a cell. Cyclins are a family of proteins that are a key component of the cell cycle regulating system, which level of expression depends on the phase of the cycle. Cyclins regulate the activity of cyclin-dependent kinases (Cdk), thanks to which they influence the length of individual phases of the cell cycle and also determine whether the cell can enter the next life stage. Proper expression of cyclins plays an important role in processes such as proliferation, transcription, DNA repair and cell differentiation. However, dysregulation of their expression is one of the most important disorders leading to the development of different types of cancer, which suggests that cyclins can be defined as a prognostic marker. Currently, we may distinguish >10 members of the cyclins family participating in the division of human cells. The group of less known cyclins includes C, F, G, H, I, J, K, L, M, O, T and Y cyclins. The present report demonstrates the current state of knowledge considering less known cyclins and their role in normal and cancer cells.
3D Texture Feature Extraction and Classification Using GLCM and LBP-Based Descriptors
Authors: Barburiceanu Stefania , Terebes Romulus , Meza Serban
Published: March 2021

Lately, 3D imaging techniques have achieved a lot of progress due to recent developments in 3D sensor technologies. This leads to a great interest regarding 3D image feature extraction and classification techniques. As pointed out in literature, one of the most important and discriminative features in images is the textural content. Within this context, we propose a texture feature extraction technique for volumetric images with improved discrimination power. The method could be used in textured volumetric data classification tasks. To achieve this, we fuse two complementary pieces of information, feature vectors derived from Local Binary Patterns (LBP) and the Gray-Level Co-occurrence Matrix-based methods. They provide information regarding the image pattern and the contrast, homogeneity and local anisotropy in the volumetric data, respectively. The performance of the proposed technique was evaluated on a public dataset consisting of volumetric textured images affected by several transformations. The classifiers used are the Support Vector Machine, k-Nearest Neighbours and Random Forest. Our method outperforms other handcrafted 3D or 2D texture feature extraction methods and typical deep-learning networks. The proposed technique improves the discrimination power and achieves promising results even if the number of images per class is relatively small.
A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children
Authors: Ciaccio Claudia , Pantaleoni Chiara , Taroni Franco , Di Bella Daniela , Magri Stefania , Lamantea Eleonora , Ghezzi Daniele , Valente Enza Maria , Nigro Vincenzo , D’Arrigo Stefano
Published: March 2021

Background: Cerebellar atrophy is a neuroradiological definition that categorizes conditions heterogeneous for clinical findings, disease course, and genetic defect. Most of the papers proposing a diagnostic workup for pediatric ataxias are based on neuroradiology or on the literature and experimental knowledge, with a poor participation of clinics in the process of disease definition. Our study aims to offer a different perspective on the way we approach cerebellar atrophy in developmental age, building a clinical-based diagnostic workup to guide molecular diagnosis. Methods: we recruited 52 patients with pediatric-onset cerebellar atrophy and definite disease categorization. Children underwent brain MRI, neurophysiological exams, metabolic investigations, and muscle biopsy with respiratory chain complex study. Single-gene sequencing, next-generation sequencing NGS panels, whole-exome sequencing (WES), and disease-specific techniques have been used to reach genetic confirmation. Results: Brain MRI is the main method of diagnosis, followed by tests on muscle biopsy and peripheral nervous system study. Other exams (e.g., metabolic investigations or evoked potentials) may be useful to narrow the list of diagnostic possibilities. Conclusions: We propose a diagnostic approach to cerebellar atrophy in children based on clinical findings, and support the evidence that a precise phenotypic definition may lead to the formulation of a definite diagnosis or otherwise guide the back phenotyping process derived from large molecular data.
Fracture Analysis for a Crack in Orthotropic Material Subjected to Combined 2i-Order Symmetrical Thermal Flux and 2j-Order Symmetrical Mechanical Loading
Authors: Wu Bing , Peng Daren , Jones Rhys
Published: March 2021

The problems of crack formation in orthotropic materials under 2i order polynomial function heat flow and 2j order polynomial function mechanical loading are considered. An extended local insulation crack model is proposed, and fracture analysis is carried out for the above problems. Utilizing Fourier transform technique (FTT) and principle of superposition, the jumps of temperature, elastic displacements on the crack, and so on are obtained. The advantage of this analysis is that the explicit closed form solutions of main parameters in classical fracture mechanics, i.e., the stress intensity factor, the energy release rate, and the energy density have been presented. A simple example is used to demonstrate the method proposed in this paper. The analysis results show that the non-dimensional thermal conductivity and the combined ratio of the heat flux per thickness perpendicular to the crack surface to the mechanical load have a great influence on the calculation of fracture parameters. Only when they meet certain conditions can the correct fracture parameter calculation results be obtained.
Health Risk of Increased O3 Concentration Based on Regional Emission Characteristics under the Unusual State of the COVID-19 Pandemic
Authors: Okazaki Yuki , Ito Lisa , Tokai Akihiro
Published: March 2021

Photochemical oxidant concentration increases with the decrease in nitrogen oxide (NOx) concentration in volatile organic compound (VOC)-sensitive areas with several automobiles and factories. We aimed to quantify the changes in health risks from ozone (O3) and nitrogen dioxide (NO2) using disability-adjusted life years (DALY) in Osaka City, which is one of the major cities in Japan. ADMER-PRO version 1.0, an atmospheric model for secondary products, was used to estimate the concentration distribution of NO2, VOC, and O3 using the year-on-year change of traffic during the declaration of the state of emergency in response to the coronavirus disease 2019 (7 April to 21 May 2020). NO2 concentration decreased by an average of 0.962 ppb in 88.9% of the grids in Osaka City, whereas O3 concentration increased by an average of 1.00 ppb in all the grids with a 26–28% reduction of traffic volume due to the pandemic. We also found three intensities for the VOC-sensitive condition depending on the different regional emission characteristics, with the DALYs of health risks from the decrease in NO2 exceeding those from the increase in O3, reaching 811.4 and 55.90 total DALYs in the city, respectively.
Spectral Decomposition and Sound Source Localization of Highly Disturbed Flow through a Severe Arterial Stenosis
Authors: Khalili Fardin , Gamage Peshala T. , Taebi Amirtahà , Johnson Mark E. , Roberts Randal B. , Mitchel John
Published: March 2021

For the early detection of atherosclerosis, it is imperative to explore the capabilities of new, effective noninvasive diagnosis techniques to significantly reduce the associated treatment costs and mortality rates. In this study, a multifaceted comprehensive approach involving advanced computational fluid dynamics combined with signal processing techniques was exploited to investigate the highly turbulent fluctuating flow through arterial stenosis. The focus was on localizing high-energy mechano-acoustic source potential to transmit to the epidermal surface. The flow analysis results showed the existence of turbulent pressure fluctuations inside the stenosis and in the post-stenotic region. After analyzing the turbulent kinetic energy and pressure fluctuations on the flow centerline and the vessel wall, the point of maximum excitation in the flow was observed around two diameters downstream of the stenosis within the fluctuating zone. It was also found that the concentration of pressure fluctuation closer to the wall was higher inside the stenosis compared to the post-stenotic region. Additionally, the visualization of the most energetic proper orthogonal decomposition (POD) mode and spectral decomposition of the flow indicated that the break frequencies ranged from 80 to 220 Hz and were correlated to the eddies generated within these regions.
Nematicidal Activity of Benzyloxyalkanols against Pine Wood Nematode
Authors: Kim Junheon , Lee Su Jin , Park Joon Oh , Yoon Kyungjae Andrew
Published: March 2021

Pine wilt disease (PWD) is caused by the pine wood nematode (PWN; Bursaphelenchus xylophilus) and causes severe environmental damage to global pine forest ecosystems. The current strategies used to control PWN are mainly chemical treatments. However, the continuous use of these reagents could result in the development of pesticide-resistant nematodes. Therefore, the present study was undertaken to find potential alternatives to the currently used PWN control agents abamectin and emamectin. Benzyloxyalkanols (BzOROH; R = C2–C9) were synthesized and the nematicidal activity of the synthetic compounds was investigated. Enzymatic inhibitory assays (acetylcholinesterase (AChE) and glutathione S-transferase (GST)) were performed with BzOC8OH and BzOC9OH to understand their mode of action. The benzyloxyalkanols showed higher nematicidal activity than did benzyl alcohol. Among the tested BzOROHs, BzC8OH and BzC9OH showed the strongest nematicidal activity. The LD50 values of BzC8OH and BzC9OH were 246.1 and 158.0 ppm, respectively. No enzyme inhibitory activity was observed for BzC8OH and BzC9OH. The results suggested that benzyloxyalcohols could be an alternative nematicidal agent.
Luteolin-Fabricated ZnO Nanostructures Showed PLK-1 Mediated Anti-Breast Cancer Activity
Authors: Kollur Shiva Prasad , Prasad Shashanka K. , Pradeep Sushma , Veerapur Ravindra , Patil Sharanagouda S. , Amachawadi Raghavendra G. , S Rajendra Prasad , Lamraoui Ghada , Al-Kheraif Abdulaziz A. , Elgorban Abdallah M. , Syed Asad , Shivamallu Chandan
Published: March 2021

The present work describes a facile and convenient procedure for synthesizing zinc oxide nanoparticles using luteolin isolated from Eclipta alba plant (L-ZnONPs) at room temperature. The formation of as-grown L-ZnONPs was confirmed by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), and selected area electron diffraction (SAED). The Wurtzite structure of ZnO was observed by its hexagonal phases in diffraction patterns. The SEM images revealed the different sizes and morphologies of L-ZnONPs, with diameters between 12 and 25 nm. The HR-TEM result showed that the inter-planar distance between two lattice fringes was 0.262 nm, which coincides with the d-spacing of (002) and (101) lattice planes of the as-obtained material. The anticancer activity of L-ZnONPs against the breast cancer cell line MCF-7 was greater as compared to that of luteolin or ZnO alone. The mechanistic evaluation of such an activity carried out using in silico methods suggested that the anti-breast cancer activity of L-ZnONPs was mediated by polo-like kinase 1 (PLK1) proteins.
High Prevalence of Insulin Resistance in Asymptomatic Patients with Acute Intermittent Porphyria and Liver-Targeted Insulin as a Novel Therapeutic Approach
Authors: Solares Isabel , Izquierdo-Sánchez Laura , Morales-Conejo Montserrat , Jericó Daniel , Castelbón Francisco Javier , Córdoba Karol Marcela , Sampedro Ana , Lumbreras Carlos , Moreno-Aliaga María Jesús , Enríquez de Salamanca Rafael , Berraondo Pedro , Fontanellas Antonio
Published: March 2021

Acute porphyria attacks are associated with the strong up-regulation of hepatic heme synthesis and over-production of neurotoxic heme precursors. First-line therapy is based on carbohydrate loading. However, altered glucose homeostasis could affect its efficacy. Our first aim was to investigate the prevalence of insulin resistance (IR) in an observational case-control study including 44 Spanish patients with acute intermittent porphyria (AIP) and 55 age-, gender- and BMI-matched control volunteers. Eight patients (18.2%) and one control (2.3%, p = 0.01) showed a high HOMA-IR index (cut-off ≥ 3.4). Patients with IR and hyperinsulinemia showed clinically stable disease. Thus, the second aim was to evaluate the effect of the co-administration of glucose and a fast-acting or new liver-targeted insulin (the fusion protein of insulin and apolipoprotein A-I, Ins-ApoAI) in AIP mice. The combination of glucose and the Ins-ApoAI promoted partial but sustained protection against hepatic heme synthesis up-regulation compared with glucose alone or co-injected with fast-acting insulin. In a prevention study, Ins-ApoAI improved symptoms associated with a phenobarbital-induced attack but maintained high porphyrin precursor excretion, probably due to the induction of hepatic mitochondrial biogenesis mediated by apolipoprotein A-I. In conclusion, a high prevalence of IR and hyperinsulinemia was observed in patients with AIP. The experimental data provide proof-of-concept for liver-targeted insulin as a way of enhancing glucose therapy for AIP.
GPR171 Activation Modulates Nociceptor Functions, Alleviating Pathologic Pain
Authors: Cho Pyung Sun , Lee Han Kyu , Choi Young In , Choi Seung In , Lim Ji Yeon , Kim Minseok , Kim Hyun , Jung Sung Jun , Hwang Sun Wook
Published: March 2021

Modulation of the function of somatosensory neurons is an important analgesic strategy, requiring the proposal of novel molecular targets. Many G-protein-coupled receptors (GPRs) have been deorphanized, but the receptor locations, outcomes due to their activations, and their signal transductions remain to be elucidated, regarding the somatosensory nociceptor function. Here we report that GPR171, expressed in a nociceptor subpopulation, attenuated pain signals via Gi/o-coupled modulation of the activities of nociceptive ion channels when activated by its newly found ligands. Administration of its natural peptide ligand and a synthetic chemical ligand alleviated nociceptor-mediated acute pain aggravations and also relieved pathologic pain at nanomolar and micromolar ranges. This study suggests that functional alteration of the nociceptor neurons by GPR171 signaling results in pain alleviation and indicates that GPR171 is a promising molecular target for peripheral pain modulation.
MicroRNA Signatures Associated with Bronchopulmonary Dysplasia Severity in Tracheal Aspirates of Preterm Infants
Authors: Siddaiah Roopa , Oji-Mmuo Christiana N. , Montes Deborah T. , Fuentes Nathalie , Spear Debra , Donnelly Ann , Silveyra Patricia
Published: March 2021

Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease that develops in neonates as a consequence of preterm birth, arrested fetal lung development, and inflammation. The incidence of BPD remains on the rise as a result of increasing survival of extremely preterm infants. Severe BPD contributes to significant health care costs and is associated with prolonged hospitalizations, respiratory infections, and neurodevelopmental deficits. In this study, we aimed to detect novel biomarkers of BPD severity. We collected tracheal aspirates (TAs) from preterm babies with mild/moderate (n = 8) and severe (n = 17) BPD, and we profiled the expression of 1048 miRNAs using a PCR array. Associations with biological pathways were determined with the Ingenuity Pathway Analysis (IPA) software. We found 31 miRNAs differentially expressed between the two disease groups (2-fold change, false discovery rate (FDR) < 0.05). Of these, 4 miRNAs displayed significantly higher expression levels, and 27 miRNAs had significantly lower expression levels in the severe BPD group when compared to the mild/moderate BPD group. IPA identified cell signaling and inflammation pathways associated with miRNA signatures. We conclude that TAs of extremely premature infants contain miRNA signatures associated with severe BPD. These may serve as potential biomarkers of disease severity in infants with BPD.
From Mitochondria to Atherosclerosis: The Inflammation Path
Authors: Suárez-Rivero Juan M. , Pastor-Maldonado Carmen J. , Povea-Cabello Suleva , Álvarez-Córdoba Mónica , Villalón-García Irene , Talaverón-Rey Marta , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Sánchez-Alcázar José A.
Published: March 2021

Inflammation is a key process in metazoan organisms due to its relevance for innate defense against infections and tissue damage. However, inflammation is also implicated in pathological processes such as atherosclerosis. Atherosclerosis is a chronic inflammatory disease of the arterial wall where unstable atherosclerotic plaque rupture causing platelet aggregation and thrombosis may compromise the arterial lumen, leading to acute or chronic ischemic syndromes. In this review, we will focus on the role of mitochondria in atherosclerosis while keeping inflammation as a link. Mitochondria are the main source of cellular energy. Under stress, mitochondria are also capable of controlling inflammation through the production of reactive oxygen species (ROS) and the release of mitochondrial components, such as mitochondrial DNA (mtDNA), into the cytoplasm or into the extracellular matrix, where they act as danger signals when recognized by innate immune receptors. Primary or secondary mitochondrial dysfunctions are associated with the initiation and progression of atherosclerosis by elevating the production of ROS, altering mitochondrial dynamics and energy supply, as well as promoting inflammation. Knowing and understanding the pathways behind mitochondrial-based inflammation in atheroma progression is essential to discovering alternative or complementary treatments.
Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR-21-5p Dysregulation in Multiple Myeloma
Authors: Algarín Esperanza M. , Quwaider Dalia , Campos-Laborie Francisco J. , Díaz-Tejedor Andrea , Mogollón Pedro , Vuelta Elena , Martín-Sánchez Montserrat , San-Segundo Laura , González-Méndez Lorena , Gutiérrez Norma C. , García-Sanz Ramón , Paíno Teresa , De Las Rivas Javier , Ocio Enrique M. , Garayoa Mercedes
Published: March 2021

BH3-mimetics targeting anti-apoptotic proteins such as MCL-1 (S63845) or BCL-2 (venetoclax) are currently being evaluated as effective therapies for the treatment of multiple myeloma (MM). Interleukin 6, produced by mesenchymal stromal cells (MSCs), has been shown to modify the expression of anti-apoptotic proteins and their interaction with the pro-apoptotic BIM protein in MM cells. In this study, we assess the efficacy of S63845 and venetoclax in MM cells in direct co-culture with MSCs derived from MM patients (pMSCs) to identify additional mechanisms involved in the stroma-induced resistance to these agents. MicroRNAs miR-193b-3p and miR-21-5p emerged among the top deregulated miRNAs in myeloma cells when directly co-cultured with pMSCs, and we show their contribution to changes in MCL-1 and BCL-2 protein expression and in the activity of S63845 and venetoclax. Additionally, direct contact with pMSCs under S63845 and/or venetoclax treatment modifies myeloma cell dependence on different BCL-2 family anti-apoptotic proteins in relation to BIM, making myeloma cells more dependent on the non-targeted anti-apoptotic protein or BCL-XL. Finally, we show a potent effect of the combination of S63845 and venetoclax even in the presence of pMSCs, which supports this combinatorial approach for the treatment of MM.
The Immune Tolerance Role of the HMGB1-RAGE Axis
Authors: Watanabe Haruki , Son Myoungsun
Published: March 2021

The disruption of the immune tolerance induces autoimmunity such as systemic lupus erythematosus and vasculitis. A chromatin-binding non-histone protein, high mobility group box 1 (HMGB1), is released from the nucleus to the extracellular milieu in particular environments such as autoimmunity, sepsis and hypoxia. Extracellular HMGB1 engages pattern recognition receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation endproducts (RAGE). While the HMGB1-RAGE axis drives inflammation in various diseases, recent studies also focus on the anti-inflammatory effects of HMGB1 and RAGE. This review discusses current perspectives on HMGB1 and RAGE’s roles in controlling inflammation and immune tolerance. We also suggest how RAGE heterodimers responding microenvironments functions in immune responses.