bluuebunny/crossref_metadata_2025 huggingface dataset:
Rock Cutting Simulation of Point Attack Picks Using the Smooth Particle Hydrodynamics Technique and the Cumulative Damage Model
Authors: Jeong Hoyoung , Choi Seungbeom , Lee Sudeuk , Jeon Seokwon
Published: August 2020

Various numerical methods have been used to simulate the rock cutting process. Numerical simulation is a useful tool for estimating the performance of a cutting tool and for understanding the mechanism of rock cutting and interaction between a cutting tool and the rock. These methods supplement the rock cutting test, which is commonly referred to as the linear cutting machine (LCM) test. Mechanical excavators, such as roadheaders, longwall shearers, and trenchers, generally use pick cutters as the cutting tool. In this study, a rock cutting simulation with a pick cutter was developed using the smooth particle hydrodynamics (SPH) technique, which is a mesh-free Lagrangian method. The Drucker–Prager (DP) strength model was used to simulate the brittle behavior of rock. The cumulative damage (CD) model was used to simulate the degraded fragmentation process of rock and the distinctive behavior of rock in the compression and tensile stress regions. In this study, an attempt was made to simulate sequential cutting by multiple pick cutters. The results showed that the numerical simulation matched the experimental results closely in terms of cutter forces, specific energy, and the fragmentation phenomenon. These results confirmed the applicability of the SPH technique in simulating the rock cutting process.
Empirical Quasi-Static and Inverse Kinematics of Cable-Driven Parallel Manipulators Including Presence of Sagging
Authors: Gia Luan Phan , Truong Thinh Nguyen
Published: August 2020

Cable-driven parallel manipulators (CDPMs) have been of great interest to researchers in recent years because they have many advantages compared to the traditional parallel robot. However, in many studies they lack the cable’s elasticity that leads to flexible cables just being considered as extendable rigid links. Furthermore, an external force acts on the extremities of cable and the self-weight is relevant to the length of it. Experimentally, a small change in length produces a huge change in tension act on the entire cable. By this property, the adjusting length of cable is often added to the traditional inverse kinematic solution in order to reduce the tension force exerted on the cable. This means that the load on the actuator is also reduced. Because of the relationship between tension that acts on the cable and its length, the kinematic problem itself does not make sense without concerning the static or dynamic problems. There is often interest in planning forces for actuators and the length of cables based on a given quasi-static trajectory of the moving platform. The mentioned problem is combined with the quasi-static problem with the inverse kinematic problem of CDPM. In this study, we introduce a novel procedure to produce the quasi-static model and inverse kinematic model for CDPM with the presence of sagging by using both an analytic approach and empirical approach. The produced model is time-efficient and is generalized for spatial CDPM. To illustrate the performance of the proposed model, the numerical and experimental approaches are employed to determine particular solutions in the feasible solutions set produced by our model in order to control the two redundant actuators’ CDPM tracking on a certain desired trajectory. Its results are clearly described in the experimental section.
Temporal Trend of PM10 and Associated Human Health Risk over the Past Decade in Cluj-Napoca City, Romania
Authors: Levei Levente , Hoaghia Maria-Alexandra , Roman Marius , Marmureanu Luminita , Moisa Corina , Levei Erika Andrea , Ozunu Alexandru , Cadar Oana
Published: August 2020

The human health risk associated with PM10 exposure was assessed for the residents of Cluj-Napoca city, Romania, for a best case-scenario based on the monthly average PM10 and for a worst-case scenario based on the monthly 90th percentile of PM10 concentration. As no toxicity value for PM10 was available, for the calculation of the hazard quotient, the toxicity value was considered to be equal to the annual limit value (40 µm/m3) set in the European Union (EU), and to air quality guidelines (20 µm/m3) set by the World Health Organization (WHO). The daily PM10 concentrations for the period 2009–2019, at the four monitoring stations existing in Cluj-Napoca, were obtained from the National Air Quality Monitoring Network. The annual PM10 values ranged between 20.3 and 29.5 µg/m3, and were below the annual limit value (40 µg/m3) set by European and national legislation, but above the annual air quality guideline (20 µg/m3) set by WHO. Generally, the monthly PM10 concentrations were higher from October to March than in the rest of the year. The monthly air quality index (AQI) showed the good to moderate quality of the air during the whole decade; however, there were days when the air quality was unhealthy for sensitive population groups. The air quality was more or less constant during the warm months, and improved significantly for the cold months from 2009 to 2019. In the best-case scenario, calculated using the EU annual limit value for PM10, the potential non-carcinogenic chronic health risk was present only in 2009 and 2010, but in the worst-case scenario, in each year there were periods, especially in the cold months, in which health risk was present. When considering the WHO air quality guidelines in the calculation of the health risk, the potential non-carcinogenic chronic health risk was present between October and March in each year in the best-case scenario, and in most of the months in the worst-case scenario.
Secondary Breakup Characteristics and Mechanism of Single Electrified Al/N-Decane Nanofluid Fuel Droplet in Electrostatic Field
Authors: Lu Heng , Li Shengji , Du Hongzhe , Lu Yibin , Huang Xuefeng
Published: August 2020

The combustion characteristics of nanofluid fuels have been widely investigated, but rare studies on the atomization were reported. Atomization is an imperative and crucial step to improve the combustion performance of nanofluid fuels, and the secondary breakup of droplets is an important segment for atomization to produce uniform fine droplets and distribute nanoparticles in each droplet. This paper firstly presents the secondary breakup characteristics of single electrified Al/n-decane nanofluid fuel droplets and revealed the mechanism of the secondary breakup. The results demonstrated that fine droplets could be produced in the electrostatic field and Al nanoparticles were distributed in each droplet. Before the breakup, the single electrified droplets experienced surface charge transportation, deformation, and Taylor cone formation. A gradient of the electric field deformed the droplet to produce the Taylor cone. As the Taylor cones were stabilized, the fluid was extruded from the tips of stable Taylor cones to produce jet filament parallel to the electric field direction and correspondingly broke up into fine sub droplets. At the nanoparticle concentration range of 1.0~10 mg/mL, the minimum average diameter of breakup sub droplets could achieve ~55.4 μm at 6.0 mg/mL. The Al nanoparticle concentration had a significant effect on the breakup performance by influencing the physical properties and charging. The order of the Charge-to-Mass ratio magnitude was 10−7~10−5 C/kg. Furthermore, the secondary breakup mechanism of single electrified nanofluid fuel droplets in the uniform electrostatic field was revealed by analyzing the droplet surface charge, deformation, Taylor cone formation, and nanoparticle concentration effect.
Evaluation of Shrimp Waste Valorization Combining Computer-Aided Simulation and Numerical Descriptive Inherent Safety Technique (NuDIST)
Authors: Zuorro Antonio , Cassiani-Cassiani Daylisney , Meza-González Demmy A. , Moreno-Sader Kariana Andrea , González-Delgado Ángel Darío
Published: August 2020

Nowadays, inherently safer designs are considered as key priorities to prevent or mitigate serious incidents with devastating consequences. The need for process safety assessment during early design phases has motivated the development of several contributions related to computer-aided assessment methodologies to measure the inherent safety of chemical processes. In this work, the large-scale production of chitosan from shrimp wastes was evaluated from a process safety point of view using the numerical descriptive inherent safety technique (NuDIST). To this end, simulation of the chitosan production was performed using Aspen Plus ® to obtain extended mass and energy balances. The assessment of all the chemicals involved within the process was carried out for the following safety parameters: explosivity (EXP), flammability (FL), and toxicity (TOX). The safety assessment of the process included the parameters of temperature (T), pressure (P), and heat of reaction (HR). The maximum chemical safety score was estimated in 171.01 with ethanol as the main contributor to the parameters of explosivity and flammability. The score associated with operating data was calculated at 209.20 and heat of reaction reported to be the most affecting parameter. The NuDIST score was estimated at 380.20. This NuDIST value revealed the low hazards associated with the handling of substances such as shrimp wastes, chitosan, and water, as well as the non-extreme temperature and pressure conditions. In general, the large-scale production of chitosan from shrimp shells was shown to be an inherently safe alternative of waste valorization.
Inspection and Classification of Semiconductor Wafer Surface Defects Using CNN Deep Learning Networks
Authors: Chien Jong-Chih , Wu Ming-Tao , Lee Jiann-Der
Published: August 2020

Due to advances in semiconductor processing technologies, each slice of a semiconductor is becoming denser and more complex, which can increase the number of surface defects. These defects should be caught early and correctly classified in order help identify the causes of these defects in the process and eventually help to improve the yield. In today’s semiconductor industry, visible surface defects are still being inspected manually, which may result in erroneous classification when the inspectors become tired or lose objectivity. This paper presents a vision-based machine-learning-based method to classify visible surface defects on semiconductor wafers. The proposed method uses deep learning convolutional neural networks to identify and classify four types of surface defects: center, local, random, and scrape. Experiments were performed to determine its accuracy. The experimental results showed that this method alone, without additional refinement, could reach a top accuracy in the range of 98% to 99%. Its performance in wafer-defect classification shows superior performance compared to other machine-learning methods investigated in the experiments.
Machine-Learning Based Optimal Seismic Control of Structure with Active Mass Damper
Authors: Chen Pei-Ching , Chien Kai-Yi
Published: August 2020

In recent years, optimal control which minimizes a cost function formulated by weighted states and control inputs has been applied to the seismic control of structures. Optimal control requires structural states which may not be available in real application; therefore, state estimation is essential, which inevitably takes additional computation time. However, time delay and state estimate error could affect the control performance. In this study, a multilayer perceptron (MLP) model and an autoregressive with exogenous inputs (ARX) model in machine learning are applied to learn the control force generated from a linear-quadratic regulator (LQR) with weighting matrices optimized by applying symbiotic organisms search algorithm. A 10-story building is adopted as a benchmark model for training and validation of the MLP and ARX models. Numerical simulation results demonstrate that the MLP and ARX models are able to emulate the LQR control force from the acceleration response directly, indicating that state estimation is not essential for optimal control implementation in real application. Finally, the machine-learning based approach is experimentally validated by conducting shake table testing in the laboratory in which the structural model is controlled by an active mass damper. The experimental results and structural control performance of the MLP and ARX models are compared with those of the LQR with a Kalman filter.
The Phase Composition and Mechanical Properties of the Novel Precipitation-Strengthening Al-Cu-Er-Mn-Zr Alloy
Authors: Amer Sayed , Yakovtseva Olga , Loginova Irina , Medvedeva Svetlana , Prosviryakov Alexey , Bazlov Andrey , Barkov Ruslan , Pozdniakov Andrey
Published: August 2020

The microstructure, phase composition, and mechanical properties during heat treatment and rolling of the novel Al-5.0Cu-3.2Er-0.9Mn-0.3Zr alloy were evaluated. A new quaternary (Al,Cu,Mn,Er) phase with possible composition Al25Cu4Mn2Er was found in the as-cast alloy. Al20Cu2Mn3 and Al3(Zr,Er) phases were nucleated during homogenization, and θ″(Al2Cu) precipitates were nucleated during aging. The metastable disc shaped θ″(Al2Cu) precipitates with a thickness of 5 nm and diameter of 100–200 nm were nucleated mostly on the Al3(Zr,Er) phase precipitates with a diameter of 35 nm. The hardness Vickers (HV) peak was found after the annealing of a rolled alloy at 150 °C due to strengthening by θ″(A2Cu) precipitates, which have a larger effect in materials hardness than do the softening processes. The novel Al-Cu-Er-Mn-Zr alloy has a yield strength (YS) of 320–332 MPa, an ultimate tensile strength (UTS) of 360–370 MPa, and an El. of 3.2–4.0% in the annealed alloy after rolling condition.
The Effect of Depth Information on Visual Complexity Perception in Three-Dimensional Textures
Authors: Li Liang , Yamada Tatsuro , Choi Woong
Published: August 2020

Visual complexity, as an attribute of images related to human perception, has been widely studied in computer science and psychology. In conventional studies, the research objects have been limited to the traditional two-dimensional (2D) patterns or images. Therefore, if depth information is introduced into this scenario, how will it affect our perception of visual complexity of an image? To answer this question, we developed an experimental virtual reality system that enables control and display of three-dimensional (3D) visual stimuli. In this study, we aimed to investigate the effect of depth information on visual complexity perception by comparing 2D and 3D displays of the same stimuli. We scanned three textures with different characteristics to create the experimental stimuli and recruited 25 participants for the experiment. The results showed that depth information significantly increased the visual complexity perception of the texture images. Moreover, depth information had different degrees of impact on visual complexity for different textures. The higher the maximum depth introduced in the 3D image, the more significant the increase in visual complexity perception. The experimental virtual reality system used in this study also provides a feasible experimental tool for future experiments.
Development and Application of Advanced Technological Solutions within Construction of Experimental Vehicle
Authors: Živčák Jozef , Puškár Michal , Brestovič Tomáš , Nagyová Anna , Palko Miroslav , Palko Maroš , Krajňáková Viktória , Ivanková Juliána , Šmajda Norbert
Published: August 2020

Changing market requirements, pressure to minimize production costs, competition, but also legislative restrictions have an impact on a number of areas, not excluding the automotive industry. Currently, development trends are moving towards the application of advanced technological solutions and materials, with the aim to reduce vehicle‘s weight, increase their strength and safety, and at the same time reduce the emission of vehicles. The Shell Eco Marathon competition is an excellent platform for the implementation of these activities. The main goal of the competition is to support the creative invention of research teams and bring innovative ideas and technical solutions. The scientific article focuses on a detailed analysis of development steps in the construction of experimental vehicles. The results of the research were presented at a competition in London 2019 with successful achievement. This work is a contribution to the design and aerodynamic optimization of the body and at the same time brings new ideas and structural elements to improve the production power unit.
Recent Advancement of Thermal Fluid Engineering in the Supercritical CO2 Power Cycle
Authors: Lee Jeong Ik , Sanchez David
Published: August 2020

The supercritical CO2 (S-CO2) power cycle is an emerging energy technology that has potential to revolutionize the conversion process of heat to mechanical or electric power [...]
A New Feature Selection Scheme for Emotion Recognition from Text
Authors: Erenel Zafer , Adegboye Oluwatayomi Rereloluwa , Kusetogullari Huseyin
Published: August 2020

This paper presents a new scheme for term selection in the field of emotion recognition from text. The proposed framework is based on utilizing moderately frequent terms during term selection. More specifically, all terms are evaluated by considering their relevance scores, based on the idea that moderately frequent terms may carry valuable information for discrimination as well. The proposed feature selection scheme performs better than conventional filter-based feature selection measures Chi-Square and Gini-Text in numerous cases. The bag-of-words approach is used to construct the vectors for document representation where each selected term is assigned the weight 1 if it exists or assigned the weight 0 if it does not exist in the document. The proposed scheme includes the terms that are not selected by Chi-Square and Gini-Text. Experiments conducted on a benchmark dataset show that moderately frequent terms boost the representation power of the term subsets as noticeable improvements are observed in terms of Accuracies.
Temporal Variability in the Response of a Linear Time-Invariant Catchment System to a Non-Stationary Inflow Concentration Field
Authors: Chang Ching-Min , Ma Kuo-Chen , Chuang Mo-Hsiung
Published: August 2020

Predicting the effects of changes in dissolved input concentration on the variability of discharge concentration at the outlet of the catchment is essential to improve our ability to address the problem of surface water quality. The goal of this study is therefore dedicated to the stochastic quantification of temporal variability of concentration fields in outflow from a catchment system that exhibits linearity and time invariance. A convolution integral is used to determine the output of a linear time-invariant system from knowledge of the input and the transfer function. This work considers that the nonstationary input concentration time series of an inert solute to the catchment system can be characterized completely by the Langevin equation. The closed-form expressions for the variances of inflow and outflow concentrations at the catchment scale are derived using the Fourier–Stieltjes representation approach. The variance is viewed as an index of temporal variability. The closed-form expressions therefore allow to evaluate the impacts of the controlling parameters on the temporal variability of outflow concentration.
Longitudinal Study on Construction Organization’s BIM Acceptance
Authors: Lee Seulki , Yu Jungho
Published: August 2020

The Korean domestic market is focused on the introduction of BIM (Building Information Modeling) owing to an influx of investment due to increased interest and mandatory application of BIM. However, the rate of BIM introduction is high, while BIM user proficiency is low. Against these problems, the authors proposed an acceptance model for BIM in construction organizations in 2012. As the number of BIM application cases increases and the number of BIM-trained users increases as time goes on, BIM users’ positive perception of BIM values are expected to increase, which may change the BIM acceptance mechanism. Therefore, we conducted a longitudinal study of the 2012 BIM acceptance model against 2019 data to estimate changes in factors affecting BIM acceptance attitudes as well as the mechanism of the relationships between factors over time spent using the technology. To generalize the results, the respondents were spread across construction sites. The data obtained 119 samples from a sample of experienced users of BIM. We used AMOS 21.0 for hypothesis testing of structural equation modeling (SEM), and the 2019 BIM acceptance model was compared against the 2012 acceptance model using an independent sample t-test. As a result, it was confirmed that the 2012 BIM acceptance model is still suitable for describing the BIM acceptance mechanism of the construction organization, and there was a difference between the 2012 model and the 2019 model. This seems to have changed the mechanism of BIM acceptance by being change perception of BIM users as time goes on. The results of this study can be used to establish a BIM activation strategy for each BIM acceptance stage and are expected to be applicable to establishing a BIM activation strategy for construction organizations or countries with similar BIM acceptance stage.
A Brief Description of Cyclic Voltammetry Transducer-Based Non-Enzymatic Glucose Biosensor Using Synthesized Graphene Electrodes
Authors: Fahmy Taha Mohamed , Ashraf Hager , Caesarendra Wahyu
Published: August 2020

The essential disadvantages of conventional glucose enzymatic biosensors such as high fabrication cost, poor stability of enzymes, pH value-dependent, and dedicated limitations, have been increasing the attraction of non-enzymatic glucose sensors research. Beneficially, patients with diabetes could use this type of sensor as a fourth-generation of glucose sensors with a very low cost and high performance. We demonstrate the most common acceptable transducer for a non-enzymatic glucose biosensor with a brief description of how it works. The review describes the utilization of graphene and its composites as new materials for high-performance non-enzymatic glucose biosensors. The electrochemical properties of graphene and the electrochemical characterization using the cyclic voltammetry (CV) technique of electrocatalysis electrodes towards glucose oxidation have been summarized. A recent synthesis method of the graphene-based electrodes for non-enzymatic glucose sensors have been introduced along with this study. Finally, the electrochemical properties such as linearity, sensitivity, and the limit of detection (LOD) for each sensor are introduced with a comparison with each other to figure out their strengths and weaknesses.
Exercise Ameliorates Insulin Resistance of Type 2 Diabetes through Motivating Short-Chain Fatty Acid-Mediated Skeletal Muscle Cell Autophagy
Authors: Yang Ling , Lin Haiqi , Lin Wentao , Xu Xiaoyang
Published: August 2020

Background: Exercise can ameliorate type II diabetes mellitus (T2DM) by regulating intestinal flora metabolites. However, the detailed mechanism needs to be further explored. Methods: A T2DM model using mice was established by feeding them a high-fat diet and giving them subsequent streptozocin injections. Fasting blood glucose and serum insulin were determined by blood glucose meter and radioimmunoassay, respectively. Intestinal flora was measured by 16sRNA sequencing. SCFA content was measured by gas chromatography (GC) or enzyme-linked immunosorbent assay (ELISA). A fluorescently labeled 2-deoxyglucose (2-NBDG) kit was employed to detect glucose uptake capacity, and western blot was utilized to explore the signaling pathway of insulin resistance and cell autophagy. Results: In the T2DM model, along with a reduction in insulin resistance (IR), exercise reversed the decline of intestinal Bacteroidetes and the increase of Firmicutes. For metabolites of Bacteroides, exercise restored the decline in total intestinal and plasma short-chain fatty acids (SCFAs) in T2DM mice. However, the administration of GLPG0974—the inhibitor of G protein-coupled receptor 43 (GPR43), which is the receptor of SCFAs—abolished exercise-mediated alleviation in IR in vivo and acetate-mediated reduction of skeletal muscle IR (SMIR) in vitro. Mechanistically, exercise induced skeletal muscle cell autophagy, thereby ameliorating SMIR, which was neutralized by GLPG0974 exposure. Conclusions: Exercise-mediated SCFAs-upregulation may ameliorate insulin resistance (IR) through increasing autophagy of skeletal muscle cells by binding to GPR43. This study provides a theoretical basis for targeting gut bacterial metabolites to prevent T2DM.
Matrix Metalloproteinases in Health and Disease
Authors: Serra Raffaele
Published: August 2020

Matrix metalloproteinases (MMPs) are members of an enzyme family and, under normal physiological conditions, are critical for maintaining tissue allostasis [...]
Development of Recombinant Immunotoxins for Hairy Cell Leukemia
Authors: Kreitman Robert J. , Pastan Ira
Published: August 2020

Hairy cell leukemia (HCL) is an indolent B-cell malignancy with excellent initial response to purine analogs pentostatin or cladribine, but patients are rarely, if ever, cured. Younger patients will usually need repeat chemotherapy which has declining benefits and increasing toxicities with each course. Targeted therapies directed to the BRAF V600E mutation and Bruton’s tyrosine kinase may be helpful, but rarely eradicate the minimal residual disease (MRD) which will eventually lead to relapse. Moxetumomab pasudotox (Moxe) is an anti-CD22 recombinant immunotoxin, which binds to CD22 on HCL cells and leads to apoptotic cell death after internalization and trafficking of the toxin to the cytosol. Phase I testing achieved a complete remission (CR) rate of 57% in relapsed/refractory HCL. Most CRs were without MRD and eradication of MRD correlated with prolonged CR duration. Patients were often MRD-free after five years. Important mild-moderate toxicities included capillary leak and hemolytic uremic syndromes which could be prevented and managed conservatively. A phase 3 trial met its endpoint of durable CR with acceptable toxicity, leading to FDA approval of Moxe for relapsed/refractory HCL, under the name Lumoxiti. Moxe combined with rituximab is currently being evaluated in relapsed/refractory HCL to improve the rate of MRD-free CR.
Epigenetic Targeting of Mcl-1 Is Synthetically Lethal with Bcl-xL/Bcl-2 Inhibition in Model Systems of Glioblastoma
Authors: Shang Enyuan , Nguyen Trang T. T. , Shu Chang , Westhoff Mike-Andrew , Karpel-Massler Georg , Siegelin Markus D.
Published: August 2020

Apoptotic resistance remains a hallmark of glioblastoma (GBM), the most common primary brain tumor in adults, and a better understanding of this process may result in more efficient treatments. By utilizing chromatin immunoprecipitation with next-generation sequencing (CHIP-seq), we discovered that GBMs harbor a super enhancer around the Mcl-1 locus, a gene that has been known to confer cell death resistance in GBM. We utilized THZ1, a known super-enhancer blocker, and BH3-mimetics, including ABT263, WEHI-539, and ABT199. Combined treatment with BH3-mimetics and THZ1 led to synergistic growth reduction in GBM models. Reduction in cellular viability was accompanied by significant cell death induction with features of apoptosis, including disruption of mitochondrial membrane potential followed by activation of caspases. Mechanistically, THZ1 elicited a profound disruption of the Mcl-1 enhancer region, leading to a sustained suppression of Mcl-1 transcript and protein levels, respectively. Mechanism experiments suggest involvement of Mcl-1 in the cell death elicited by the combination treatment. Finally, the combination treatment of ABT263 and THZ1 resulted in enhanced growth reduction of tumors without induction of detectable toxicity in two patient-derived xenograft models of GBM in vivo. Taken together, these findings suggest that combined epigenetic targeting of Mcl-1 along with Bcl-2/Bcl-xL is potentially therapeutically feasible.
Multiplex Digital PCR to Detect Amplifications of Specific Androgen Receptor Loci in Cell-Free DNA for Prognosis of Metastatic Castration-Resistant Prostate Cancer
Authors: Du Meijun , Huang Chiang-Ching , Tan Winston , Kohli Manish , Wang Liang
Published: August 2020

Amplification of androgen receptor (AR) is a common genomic event in metastatic castration-resistant prostate cancer (mCRPC). To evaluate the prognostic value of the amplifications of specific loci in the AR gene in cell-free DNA, we developed a multiplex digital PCR (dPCR) assay that targeted AR enhancer (AR-En), AR exon 1 (AR-E1), AR exon 8 (AR-E8) and OPHN1 (downstream of AR). We selected three relatively stable genes, C2orf16, FAM111B, and GRIA3, as reference controls for copy number normalization. One hundred and eight mCRPC patients were recruited to test the association of specific AR loci amplification with clinical outcome. Using a normalized ratio ≥ 1.92 as cutoff, amplification of AR-En, AR-E1, AR-E8 and OPHN1 was observed in 28, 25, 24 and 19 of 108 mCRPC patients, respectively. Among the 41 patients with AR region amplification, 9 (21.9%) showed amplification at all four selected regions and 15 (36.6%) showed amplification at AR-En, AR-E1, and AR-E8. Six (14.6%) patients showed independent AR-En amplification, while the remaining 3 (7.3%) demonstrated AR-E8 amplification only. Kaplan–Meier analysis showed overall survival’s association with the amplification of AR-En (p = 0.02, HR = 1.68 (1.07–2.65)), AR-E8 (p = 0.02, HR = 1.78 (1.08–2.92)) and AR-En-E8 (the combination of AR-En and AR-E8 (p = 0.009, HR = 1.77 (1.15–2.73)). Multivariate models that included AR-En-E8 amplification and clinical factors significantly improved prognostic performance (p = 0.0001). With further validation, the multiplex dPCR assay may assist in prognostication of mCRPC patients.
Stable Isotope Tracing Metabolomics to Investigate the Metabolic Activity of Bioactive Compounds for Cancer Prevention and Treatment
Authors: Choudhury Feroza K. , Hackman G. Lavender , Lodi Alessia , Tiziani Stefano
Published: August 2020

A major hallmark of cancer is the metabolic reprogramming of cancer cells to fuel tumor growth and proliferation. Various plant-derived bioactive compounds efficiently target the metabolic vulnerabilities of cancer cells and exhibit potential as emerging therapeutic agents. Due to their safety and common use as dietary components, they are also ideal for cancer prevention. However, to render their use as efficient as possible, the mechanism of action of these phytochemicals needs to be well characterized. Stable isotope tracing is an essential technology to study the molecular mechanisms by which nutraceuticals modulate and target cancer metabolism. The use of positionally labeled tracers as exogenous nutrients and the monitoring of their downstream metabolites labeling patterns enable the analysis of the specific metabolic pathway activity, via the relative production and consumption of the labeled metabolites. Although stable isotope tracing metabolomics is a powerful tool to investigate the molecular activity of bioactive compounds as well as to design synergistic nutraceutical combinations, this methodology is still underutilized. This review aims to investigate the research efforts and potentials surrounding the use of stable isotope tracing metabolomics to examine the metabolic alterations mediated by bioactive compounds in cancer.
Structure of Nanocrystalline, Partially Disordered MoS2+δ Derived from HRTEM—An Abundant Material for Efficient HER Catalysis
Authors: Ronge Emanuel , Hildebrandt Sonja , Grutza Marie-Luise , Klein Helmut , Kurz Philipp , Jooss Christian
Published: August 2020

Molybdenum sulfides (MoSx, x > 2) are promising catalysts for the hydrogen evolution reaction (HER) that show high hydrogen evolution rates and potentially represent an abundant alternative to platinum. However, a complete understanding of the structure of the most active variants is still lacking. Nanocrystalline MoS2+δ was prepared by a solvothermal method and immobilized on graphene. The obtained electrodes exhibit stable HER current densities of 3 mA cm−2 at an overpotential of ~200 mV for at least 7 h. A structural analysis of the material by high-resolution transmission electron microscopy (HRTEM) show partially disordered nanocrystals of a size between 5–10 nm. Both X-ray and electron diffraction reveal large fluctuations in lattice spacing, where the average c-axis stacking is increased and the in-plane lattice parameter is locally reduced in comparison to the layered structure of crystalline MoS2. A three-dimensional structural model of MoS2+δ could be derived from the experiments, in which [Mo2S12]2− and [Mo3S13]2− clusters as well as disclinations represent the typical defects in the ideal MoS2 structure. It is suggested that the partially disordered nanostructure leads to a high density of coordinatively modified Mo sites with lower Mo–Mo distances representing the active sites for HER catalysis, and, that these structural features are more important than the S:Mo ratio for the activity.
The Secret Garden of Neuronal circRNAs
Authors: Gasparini Silvia , Licursi Valerio , Presutti Carlo , Mannironi Cecilia
Published: August 2020

High-throughput transcriptomic profiling approaches have revealed that circular RNAs (circRNAs) are important transcriptional gene products, identified across a broad range of organisms throughout the eukaryotic tree of life. In the nervous system, they are particularly abundant, developmentally regulated, region-specific, and enriched in genes for neuronal proteins and synaptic factors. These features suggested that circRNAs are key components of an important layer of neuronal gene expression regulation, with known and anticipated functions. Here, we review major recognized aspects of circRNA biogenesis, metabolism and biological activities, examining potential new functions in the context of the nervous system.
Cholesterol and Mevalonate: Two Metabolites Involved in Breast Cancer Progression and Drug Resistance through the ERRα Pathway
Authors: Brindisi Matteo , Fiorillo Marco , Frattaruolo Luca , Sotgia Federica , Lisanti Michael P. , Cappello Anna Rita
Published: August 2020

Breast cancer is the second greatest cause of cancer-related death in women. Resistance to endocrine treatments or chemotherapy is a limiting drawback. In this context, this work aims to evaluate the effects of cholesterol and mevalonate during tumor progression and their contribution in the onset of resistance to clinical treatments in use today. In this study, we demonstrated that cholesterol and mevalonate treatments were able to activate the estrogen-related receptor alpha (ERRα) pathway, increasing the expression levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), ERbB2/human epithelial receptor (HER2), tumor protein D52 (TPD52), and NOTCH2 proteins in breast cancer cells. The activation of this pathway is shown to be responsible for intense metabolic switching, higher proliferation rates, sustained motility, the propagation of cancer stem-like cells (CSCs), and lipid droplet formation. All of these events are related to greater tumor propagation, aggressiveness, and drug resistance. Furthermore, the activation and expression of proteins induced by the treatment with cholesterol or mevalonate are consistent with those obtained from the MCF-7/TAMr cell line, which is largely used as a breast cancer model of acquired endocrine therapy resistance. Altogether, our data indicate that cholesterol and mevalonate are two metabolites implicated in breast cancer progression, aggressiveness, and drug resistance, through the activation of the ERRα pathway. Our findings enable us to identify the ERRα receptor as a poor prognostic marker in patients with breast carcinoma, suggesting the correlation between cholesterol/mevalonate and ERRα as a new possible target in breast cancer treatment.
Tat-Cannabinoid Receptor Interacting Protein Reduces Ischemia-Induced Neuronal Damage and Its Possible Relationship with 14-3-3η
Authors: Kwon Hyun Jung , Kim Duk-Soo , Kim Woosuk , Jung Hyo Young , Yu Yeon Hee , Ju Young In , Park Dae-Kyoon , Hwang In Koo , Kim Dae Won , Yoo Dae Young
Published: August 2020

Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the C-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H2O2-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H2O2 treatment in HT22 cells. Ischemia–reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.
Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions
Authors: Carenzo Andrea , Serafini Mara S. , Roca Elisa , Paderno Alberto , Mattavelli Davide , Romani Chiara , Saintigny Pierre , Koljenović Senada , Licitra Lisa , De Cecco Loris , Bossi Paolo
Published: August 2020

Background: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS). Materials and methods: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan–Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis. Results: Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, p = 0.0052) and they expressed four enriched hallmarks: “TGF beta signaling” “angiogenesis”, “unfolded protein response”, “apical junction”. Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters. Conclusions: Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs.
Dozy-Chaos Mechanics for a Broad Audience
Authors: Egorov Vladimir V.
Published: August 2020

A new and universal theoretical approach to the dynamics of the transient state in elementary physico-chemical processes, called dozy-chaos mechanics (Egorov, V.V. Heliyon Physics2019, 5, e02579), is introduced to a wide general readership.
Corrosion Modeling of Magnesium and Its Alloys for Biomedical Applications: Review
Authors: Abdalla Moataz , Joplin Alexander , Elahinia Mohammad , Ibrahim Hamdy
Published: August 2020

Biodegradable metals have been under significant research as promising alternatives to the currently in-use nonbiodegradable materials in the field of supportive medical implants. In this scope, magnesium and its alloys were widely investigated due to their superior biocompatibility over other metals. Most of the research effort in the literature has been focused on assuring the biocompatibility, improving mechanical properties, and tailoring the corrosion rate of magnesium-based implants. Furthermore, considerable research was done to develop numerical models towards an inexpensive and fast designing tools capable of simulating the degradation/corrosion behavior of magnesium-based implants. Due to the complexity of the degradation process and the various factors that can be involved, several hypotheses were introduced to provide a realistic simulation of the corrosion behavior in vitro and in vivo. A review of the current literature hypothesis and different modeling constitutive equations for modeling the corrosion of magnesium alloys along with a summary of the supplementary experimental methods is provided in this paper.
Controlling the Structural, Mechanical and Frictional Properties of MoSx Coatings by High-Power Impulse Magnetron Sputtering
Authors: Kokalj David , Debus Jörg , Stangier Dominic , Moldenhauer Henning , Nikolov Alexander , Wittig Alexandra , Brümmer Andreas , Tillmann Wolfgang
Published: August 2020

Tribology, as the science and technology of interacting surfaces, typically relies on liquid lubricants which reduce friction and wear. For environmentally friendly tribological purposes and applications requiring a liquid-free performance, solid lubricants, such as MoS2 coatings, play an essential role. It is crucial to understand the interplay between the parameters of the coating synthesis and the characteristics of the coating. The impact of the deposition parameters on the structural, mechanical and frictional properties of MoSx thin films, which are synthesized by high-power impulse magnetron sputtering, are studied. The morphology, topography and stoichiometry (2.02 < x < 2.22) of the films are controlled by, in particular, the bias-voltage and heating power applied during the sputtering process. In combination with a low pulse frequency the hardness and elastic stiffness of the MoSx films are enhanced up to 2 and 90 GPa, respectively. This enhancement is assigned to a shortening of the Mo-S bonding lengths and a strengthening in the interatomic coupling as well as to a formation of small-sized crystallites at the surface. The friction coefficient reduces to µ = 0.10 for films with an initial (100) orientation and the mean roughness of the MoSx films decreases below 15 nm by shortening the cathode pulses.
Protruding Nanostructured Surfaces for Antimicrobial and Osteogenic Titanium Implants
Authors: Ishak Mohd I. , Liu Xiayi , Jenkins Joshua , Nobbs Angela H. , Su Bo
Published: August 2020

Protruding nanostructured surfaces have gained increasing interest due to their unique wetting behaviours and more recently their antimicrobial and osteogenic properties. Rapid development in nanofabrication techniques that offer high throughput and versatility on titanium substrate open up the possibility for better orthopaedic and dental implants that deter bacterial colonisation while promoting osteointegration. In this review we present a brief overview of current problems associated with bacterial infection of titanium implants and of efforts to fabricate titanium implants that have both bactericidal and osteogenic properties. All of the proposed mechano-bactericidal mechanisms of protruding nanostructured surfaces are then considered so as to explore the potential advantages and disadvantages of adopting such novel technologies for use in future implant applications. Different nanofabrication methods that can be utilised to fabricate such nanostructured surfaces on titanium substrate are briefly discussed.
Microstructure Characterization and Corrosion Resistance of Zinc Coating Obtained in a Zn-AlNiBi Galvanizing Bath
Authors: Kania Henryk , Saternus Mariola , Kudláček Jan , Svoboda Jakub
Published: August 2020

The article examines the impact of the addition of Al, Ni, and Bi to a zinc bath on the microstructure and corrosion resistance of hot dip galvanizing coatings. The microstructure on the surface and the cross-section of the coatings obtained in the Zn-AlNiBi bath were examined. The corrosion resistance of the coatings was assessed by the standard neutral salt spray test (EN ISO 9227), the sulfur dioxide test in a humid atmosphere (EN ISO 6988), and the electrochemical test. The corrosion resistance of Zn-AlNiBi coatings was compared with the corrosion resistance of coatings attained in the bath of “pure” zinc. The corrosion tests showed higher corrosion wear of the coating obtained in the Zn-AlNiBi bath and a higher value of the corrosion current density for this coating. It was found that the cause of the reduction of the corrosion resistance of the coating, in contrast to the coating obtained in the “pure” zinc bath, may be the presence of bismuth precipitates in the coating, which may form additional corrosion cells.
On the Solution of Equations by Extended Discretization
Authors: Argyros Gus I. , Argyros Michael I. , Regmi Samundra , Argyros Ioannis K. , George Santhosh
Published: August 2020

The method of discretization is used to solve nonlinear equations involving Banach space valued operators using Lipschitz or Hölder constants. But these constants cannot always be found. That is why we present results using ω− continuity conditions on the Fréchet derivative of the operator involved. This way, we extend the applicability of the discretization technique. It turns out that if we specialize ω− continuity our new results improve those in the literature too in the case of Lipschitz or Hölder continuity. Our analysis includes tighter upper error bounds on the distances involved.