bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid Machine Learning Model for Body Fat Percentage Prediction Based on Support Vector Regression and Emotional Artificial Neural Networks
Authors: Hussain Solaf A. , Cavus Nadire , Sekeroglu Boran
Published: October 2021

Obesity or excessive body fat causes multiple health problems and diseases. However, obesity treatment and control need an accurate determination of body fat percentage (BFP). The existing methods for BFP estimation require several procedures, which reduces their cost-effectivity and generalization. Therefore, developing cost-effective models for BFP estimation is vital for obesity treatment. Machine learning models, particularly hybrid models, have a strong ability to analyze challenging data and perform predictions by combining different characteristics of the models. This study proposed a hybrid machine learning model based on support vector regression and emotional artificial neural networks (SVR-EANNs) for accurate recent BFP prediction using a primary BFP dataset. SVR was applied as a consistent attribute selection model on seven properties and measurements, using the left-out sensitivity analysis, and the regression ability of the EANN was considered in the prediction phase. The proposed model was compared to seven benchmark machine learning models. The obtained results show that the proposed hybrid model (SVR-EANN) outperformed other machine learning models by achieving superior results in the three considered evaluation metrics. Furthermore, the proposed model suggested that abdominal circumference is a significant factor in BFP prediction, while age has a minor effect.
Estimating Directed Phase-Amplitude Interactions from EEG Data through Kernel-Based Phase Transfer Entropy
Authors: De La Pava Panche Iván , Gómez-Orozco Viviana , Álvarez-Meza Andrés , Cárdenas-Peña David , Orozco-Gutiérrez Álvaro
Published: October 2021

Cross-frequency interactions, a form of oscillatory neural activity, are thought to play an essential role in the integration of distributed information in the brain. Indeed, phase-amplitude interactions are believed to allow for the transfer of information from large-scale brain networks, oscillating at low frequencies, to local, rapidly oscillating neural assemblies. A promising approach to estimating such interactions is the use of transfer entropy (TE), a non-linear, information-theory-based effective connectivity measure. The conventional method involves feeding instantaneous phase and amplitude time series, extracted at the target frequencies, to a TE estimator. In this work, we propose that the problem of directed phase-amplitude interaction detection is recast as a phase TE estimation problem, under the hypothesis that estimating TE from data of the same nature, i.e., two phase time series, will improve the robustness to the common confounding factors that affect connectivity measures, such as the presence of high noise levels. We implement our proposal using a kernel-based TE estimator, defined in terms of Renyi’s α entropy, which has successfully been used to compute single-trial phase TE. We tested our approach on the synthetic data generated through a simulation model capable of producing a time series with directed phase-amplitude interactions at two given frequencies, and on EEG data from a cognitive task designed to activate working memory, a memory system whose underpinning mechanisms are thought to include phase–amplitude couplings. Our proposal detected statistically significant interactions between the simulated signals at the desired frequencies for the synthetic data, identifying the correct direction of the interaction. It also displayed higher robustness to noise than the alternative methods. The results attained for the working memory data showed that the proposed approach codes connectivity patterns based on directed phase–amplitude interactions, that allow for the different cognitive load levels of the working memory task to be differentiated.
Analysis of Thermomechanical Stresses of a Photovoltaic Panel Using a Passive System of Cooling
Authors: Pérez Escobar Brayan L. , Pérez Hernández Germán , Ocampo Ramírez Arturo , Rojas Blanco Lizeth , Díaz Flores Laura L. , Vidal Asencio Inocente , Hernández Perez José G. , Ramírez Morales Erik
Published: October 2021

In this paper, the gradient temperature and the thermomechanical stresses of a photovoltaic panel has been studied with and without heatsink. For this purpose, a three-dimensional analysis was carried out. Accordingly, a heat transfer analysis was developed. The numerical results show a cooling close to 26.7% with the proposed triangle fins compared with the rectangular fins studied before by another author, and the temperature distribution was determined. With this information, the stress analysis was carried out in order to find the effect on the panel due to the thermomechanical stresses. The aluminium frame was restricted to move freely. The resulting stresses field established the magnitude of the alternative stresses, resulting in a 6.7% drop compared with a reference panel. The guidelines of IEC 61215 have to be take into account. Due to the results obtained, the use of this kind of system in desert conditions is desirable because of its high operational temperature and due to the increase in heat transfer by the fins.
Experimental Testing of Passive Linear TMD for Postural Tremor Attenuation
Authors: Gebai Sarah , Hammoud Mohammad , Cumunel Gwendal , Foret Gilles , Roze Emmanuel , Hainque Elodie
Published: October 2021

Research interest to provide a mechanical solution for involuntary tremors is increasing due to the severe side effects caused by the medications used to lessen its symptoms. This paper deals with the design of a cantilever-type tuned mass damper (TMD) used to prove the effectiveness of passive controllers in reducing the involuntary tremor’s vibrational signals transmitted by the muscles to the hand segment. TMD is tested on an experimental arm, reflecting the flexion-extension motion of the wrist, excited by a mechanical shaker with the measured tremor signal of a patient with essential tremor. The designed TMD provides a new operational frequency for each position of the screw fixed to its beam. Modal damping ratios are also calculated using different methods for each position. The effectiveness of the TMD is quantified by measurements using a vibrometer and inertial measurement unit. Three TMDs, representing 15.7% total mass ratio, cause a reduction of 29% for the acceleration, 69% for the velocity, 79% for the displacement, 67% for the angular velocity, and 82% for the angular displacement signals. These encouraging results will allow the improvement of the design of the passive controller in the form of a wearable bracelet suitable for daily life.
Cybersecurity of Microgrid: State-of-the-Art Review and Possible Directions of Future Research
Authors: Jamil Norziana , Qassim Qais Saif , Bohani Farah Aqilah , Mansor Muhamad , Ramachandaramurthy Vigna Kumaran
Published: October 2021

The infrastructure of and processes involved in a microgrid electrical system require advanced technology to facilitate connection among its various components in order to provide the intelligence and automation that can benefit users. As a consequence, the microgrid has vulnerabilities that can expose it to a wide range of attacks. If they are not adequately addressed, these vulnerabilities may have a destructive impact on a country’s critical infrastructure and economy. While the impact of exploiting vulnerabilities in them is understood, research on the cybersecurity of microgrids is inadequate. This paper provides a comprehensive review of microgrid cybersecurity. In particular, it (1) reviews the state-of-the-art microgrid electrical systems, communication protocols, standards, and vulnerabilities while highlighting prevalent solutions to cybersecurity-related issues in them; (2) provides recommendations to enhance the security of these systems by segregating layers of the microgrid, and (3) identifies the gap in research in the area, and suggests directions for future work to enhance the cybersecurity of microgrids.
Characterization of Infant Cardiopulmonary Resuscitation Delivery with Range Sensor Feedback on Performance
Authors: Alkhafaji Farah M. , Khalid Ghaidaa A. , Al-Naji Ali , Hussein Basheer M. , Chahl Javaan
Published: October 2021

Cardiac arrest (CA) in infants is an issue worldwide, which causes significant morbidity and mortality rates. Cardiopulmonary resuscitation (CPR) is a technique performed in case of CA to save victims’ lives. However, CPR is often not performed effectively, even when delivered by qualified rescuers. Therefore, international guidelines have proposed applying a CPR feedback device to achieve high-quality application of CPR to enhance survival rates. Currently, no feedback device is available to guide learners through infant CPR performance in contrast to a number of adult CPR feedback devices. This study presents a real-time feedback system to improve infant CPR performance by medical staff and laypersons using a commercial CPR infant manikin. The proposed system uses an IR sensor to compare CPR performance obtained with no feedback and with a real-time feedback system. Performance was validated by analysis of the CPR parameters actually delivered against the recommended target parameters. Results show that the real-time feedback system significantly improves the quality of chest compression parameters. The two-thumb compression technique is the achievable and appropriate mechanism applied to infant subjects for delivering high-quality CPR. Under the social distancing constraints imposed by the SARS-CoV-2 pandemic, the results from the training device were sent to a CPR training center and provided each participant with CPR proficiency.
Lab Scale Implementation of Industry 4.0 for an Automatic Yogurt Filling Production System—Experimentation, Modeling and Process Optimization
Authors: Salah Bashir , Khan Razaullah , Ramadan Muawia , Ahmad Rafiq , Saleem Waqas
Published: October 2021

Currently, Industry 4.0 is word of mouth, and its implementation has gained increased attention from industrial and academic researchers, entrepreneurs, and service providers all over the world. With Industry 4.0, the integration of facilities and products enables real-time data exchange, and the overall production system becomes self-reliant and intelligent to predict and maintain its operational performance. In this research, the lab-scale implementation of Industry 4.0 is implemented for an automatic yogurt filling production system. A mathematical model for the process optimization of Industry 4.0 was also developed. A real-life problem was solved optimally using linear programming techniques with the objective of maximizing the speed of the conveyor belt. Moreover, the sequencing of processing orders using single-dimensional rules was performed. The effects of changes in the feed rate of the yogurt valve and length of the conveyor belt on the feed rate of the flavor valve, speed of conveyor belt, waiting time, processing times, and the different performance measures were investigated at the end.
Dosimetric Optimization of a Laser-Driven Irradiation Facility Using the G4-ELIMED Application
Authors: Mingo Barba Sergio , Schillaci Francesco , Catalano Roberto , Petringa Giada , Margarone Daniele , Cirrone Giuseppe Antonio Pablo
Published: October 2021

ELIMED has been developed and installed at ELI beamlines as a part of the ELIMAIA beamline to transport, monitor, and use laser-driven ion beams suitable for multidisciplinary applications, including biomedical ones. This paper aims to investigate the feasibility to perform radiobiological experiments using laser-accelerated proton beams with intermediate energies (up to 30 MeV). To reach this goal, we simulate a proton source based on experimental data like the ones expected to be available in the first phase of ELIMED commissioning by using the G4-ELIMED application (an application based on the Geant4 toolkit that simulates the full ELIMED beamline). This allows the study of transmission efficiency and the final characteristics of the proton beam at the sample irradiation point. The Energy Selector System is used as an active energy modulator to obtain the desired beam features in a relatively short irradiation time (around 6 min). Furthermore, we demonstrate the capability of the beamline to filter out other ion contaminants, typically co-accelerated in a laser-plasma environment. These results can be considered as a detailed feasibility study for the use of ELIMED for various user applications such as radiobiological experiments with ultrahigh dose rate proton beams.
Self-Tuning Lam Annealing: Learning Hyperparameters While Problem Solving
Authors: Cicirello Vincent A.
Published: October 2021

The runtime behavior of Simulated Annealing (SA), similar to other metaheuristics, is controlled by hyperparameters. For SA, hyperparameters affect how “temperature” varies over time, and “temperature” in turn affects SA’s decisions on whether or not to transition to neighboring states. It is typically necessary to tune the hyperparameters ahead of time. However, there are adaptive annealing schedules that use search feedback to evolve the “temperature” during the search. A classic and generally effective adaptive annealing schedule is the Modified Lam. Although effective, the Modified Lam can be sensitive to the scale of the cost function, and is sometimes slow to converge to its target behavior. In this paper, we present a novel variation of the Modified Lam that we call Self-Tuning Lam, which uses early search feedback to auto-adjust its self-adaptive behavior. Using a variety of discrete and continuous optimization problems, we demonstrate the ability of the Self-Tuning Lam to nearly instantaneously converge to its target behavior independent of the scale of the cost function, as well as its run length. Our implementation is integrated into Chips-n-Salsa, an open-source Java library for parallel and self-adaptive local search.
Long-Term Monitored Road Degradation Functions as a Tool to Increase Quality of Pavement Design
Authors: Sedivy Stefan , Mikulova Lenka , Danisovic Peter , Sramek Juraj , Remek Lubos , Kozel Matus
Published: October 2021

Ensuring the sustainability of road infrastructure cannot be achieved without the continuous application of new knowledge and approaches within individual management steps. A particularly risky stage in the life cycle of existing roads is the operation phase. High attention is paid to the environmental, financial and social impacts and benefits of individual processes applied by road managers. These processes meet in pavement management systems (PMS), which, however, cannot work reliably without the necessary input data. Information on the development of the technical condition of the road can also be included among the most important data. The paper brings the first outputs from several years of research of measurements on the Slovak 1st class road. Its aim is to gradually determine the degradation functions for the needs of Slovak geographical, climatic and transport conditions. The secondary objective is to verify the reliability of non-destructive measurement procedures of the technical condition of the road. Emphasis is placed on the application of such mathematical procedures that can not only reliably bring about the determination of past developments in the roadway, but can also present the expected picture of future developments.
Docosahexaenoic Acid and Eicosapentaenoic Acid Intakes Modulate the Association of FADS2 Gene Polymorphism rs526126 with Plasma Free Docosahexaenoic Acid Levels in Overweight Children
Authors: Mihailescu Alexandra , Serafim Vlad , Paul Corina , Andreescu Nicoleta , Tiugan Diana-Andreea , Tutac Paul , Velea Iulian , Zimbru Cristian G. , Serban Costela Lacrimioara , Ion Adina Iuliana , David Vlad Laurentiu , Ionescu Alin , Puiu Maria , Niculescu Mihai Dinu
Published: October 2021

Polyunsaturated fatty acids are involved in a wide variety of biological functions. Linoleic acid and alpha-linolenic acid are two essential fatty acids that the body cannot synthesize. The conversion rates in the body depend on FADS2 genetic variants. Certain variations in this gene are directly responsible for the low levels and poor conversion efficiency of the delta-6 desaturase enzyme, resulting in low circulating levels of docosahexaenoic acid. In this study, we evaluated the impact of the rs526126 FADS2 gene polymorphism on fatty acid levels in a group of two hundred children (n = 95 males, n = 105 females) aged 7–18 years, with obesity defined by BMI > +2 SD. Fatty acid quantification was performed by LC-MS/MS while genotyping for genetic variants was performed using a custom-made hotspot sequencing panel of 55 SNPs. Our results suggest that rs526126 FADS2 gene polymorphism specifically impacts the plasma levels of free n-3 polyunsaturated fatty acids. Finally, the presence of the minor allele G of rs526126 could have beneficial effects, as it was associated with higher levels of free docosahexaenoic acid in plasma, especially in children with low n-3 intakes.
Parallel-Structure Deep Learning for Prediction of Remaining Time of Process Instances
Authors: Wahid Nur Ahmad , Bae Hyerim , Adi Taufik Nur , Choi Yulim , Iskandar Yelita Anggiane
Published: October 2021

Event logs generated by Process-Aware Information Systems (PAIS) provide many opportunities for analysis that are expected to help organizations optimize their business processes. The ability to monitor business processes proactively can allow an organization to achieve, maintain or enhance competitiveness in the market. Predictive Business Process Monitoring (PBPM) can provide measures such as the prediction of the remaining time of an ongoing process instance (case) by taking past activities in running process instances into account, as based on the event logs of previously completed process instances. With the prediction provided, we expect that organizations can respond quickly to deviations from the desired process. In the context of the growing popularity of deep learning and the need to utilize heterogeneous representation of data; in this study, we derived a new deep-learning approach that utilizes two types of data representation based on a parallel-structure model, which consists of a convolutional neural network (CNN) and a multi-layer perceptron (MLP) with an embedding layer, to predict the remaining time. Conducting experiments with real-world datasets, we compared our proposed method against the existing deep-learning approach to confirm its utility for the provision of more precise prediction (as indicated by error metrics) relative to the baseline method.
Performance of Scoring Systems in Predicting Clinical Outcomes in Patients with Bacteremia of Listeria monocytogenes: A 9-Year Hospital-Based Study
Authors: Huang Shang-Hsuan , Hsieh Ming-Shun , Hu Sung-Yuan , Huang Shih-Che , Tsai Che-An , Hsu Chiann-Yi , Lin Tzu-Chieh , Lee Yi-Chen , Liao Shu-Hui
Published: October 2021

Background: Listeria monocytogenes (LM) is a facultative anaerobe, Gram-positive bacillus which is widely distributed in nature, and can be separated from soil, water, and rotten vegetables. Immunocompetent people are less likely to suffer from LM infection or may only show gastrointestinal symptoms. However, immunocompromised elderly people, pregnant women, and newborns may develop life-threatening invasive infections. The mortality rate of LM infection is as high as 25–30%. The aim of this study is to investigate clinical scores of patients with bacteremia of LM confirmed by one or more blood cultures. We analyzed their demographics and laboratory findings in relation to their clinical outcomes. Materials and Methods: This was a hospital-based retrospective study on patients with bacteremia of LM. Data were collected from the electronic clinical database of Taichung Veterans General Hospital between January 2012 and December 2020. Bacteremia of LM was confirmed by at least one blood culture. Demographics, clinical characteristics, and laboratory data were collected for analysis. A variety of clinical scoring systems were used to predict the clinical outcome. Results: A total of 39 patients had confirmed bacteremia of LM. Among them, 1 neonatal patient was excluded. The remaining 38 patients were studied. They included 16 males (42.1%) and 22 females (57.9%), with a mean age of 59.9 ± 19.6 years. Their hospital stay averaged 23.3 ± 20.9 days. The in-hospital mortality rate was 36.8%. Mortality in Emergency Department Sepsis (MEDS) Score was 6.6 ± 4.0 for survivors and 12.4 ± 4.4 for non-survivors (P < 0.001). The National Early Warning Score (NEWS) was 3.9 ± 2.8 for survivors and 7.8 ± 3.1 for non-survivors (P = 0.001). Regarding the prediction of mortality risk, the AUC of ROC was 0.829 for MEDS and 0.815 for NEWS. Conclusions: MEDS and NEWS were both good predictors of the clinical outcome in LM bacteremic patients. In those with higher scores of MEDS (≥10) and NEWS (≥8), we recommended an early goal-directed therapy and appropriate antibiotic treatment as early as possible to reduce mortality. Further large-scale studies are required to gain a deeper understanding of this disease and to ensure patient safety.
Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression
Authors: Tolg Cornelia , Messam Britney Jodi-Ann , McCarthy James Benjamin , Nelson Andrew Cook , Turley Eva Ann
Published: October 2021

Signaling from an actively remodeling extracellular matrix (ECM) has emerged as a critical factor in regulating both the repair of tissue injuries and the progression of diseases such as metastatic cancer. Hyaluronan (HA) is a major component of the ECM that normally functions in tissue injury to sequentially promote then suppress inflammation and fibrosis, a duality in which is featured, and regulated in, wound repair. These essential response-to-injury functions of HA in the microenvironment are hijacked by tumor cells for invasion and avoidance of immune detection. In this review, we first discuss the numerous size-dependent functions of HA and emphasize the multifunctional nature of two of its receptors (CD44 and RHAMM) in regulating the signaling duality of HA in excisional wound healing. This is followed by a discussion of how HA metabolism is de-regulated in malignant progression and how targeting HA might be used to better manage breast cancer progression.
The Evolving Concept of Neuro-Thromboinflammation for Neurodegenerative Disorders and Neurotrauma: A Rationale for PAR1-Targeting Therapies
Authors: Festoff Barry W. , Dockendorff Chris
Published: October 2021

Interest in the role of coagulation and fibrinolysis in the nervous system was active in several laboratories dating back before cloning of the functional thrombin receptor in 1991. As one of those, our attention was initially on thrombin and plasminogen activators in synapse formation and elimination in the neuromuscular system, with orientation towards diseases such as amyotrophic lateral sclerosis (ALS) and how clotting and fibrinolytic pathways fit into its pathogenesis. This perspective is on neuro-thromboinflammation, emphasizing this emerging concept from studies and reports over more than three decades. It underscores how it may lead to novel therapeutic approaches to treat the ravages of neurotrauma and neurodegenerative diseases, with a focus on PAR1, ALS, and parmodulins.
Direct Extraction of Fumaric Acid from Rhizopus oryzae Suspensions—Interfacial Mass Transfer
Authors: Cascaval Dan , Galaction Anca-Irina , Tucaliuc Alexandra , Kloetzer Lenuta
Published: October 2021

Experimental studies on the reactive extraction of fumaric acid with Amberlite LA-2 from Rhizopus oryzae suspensions using three solvents with different dielectric constants varying from 9.08 to 1.90 (dichloromethane, n-butyl acetate, and n-heptane, respectively) underlined the particular behavior of the extraction system in the presence of fungal biomass. The interfacial mass flow of the reaction product was found to be significantly affected by the biomass, due mainly to its adsorption onto the phase separation interface, this leading to the appearance of a physical barrier against the solute’s transfer. However, the magnitude of the adsorption phenomenon was found to depend on Rhizopus oryzae’s affinity for the solvent phase, which increased significantly from dichloromethane to n-heptane. The negative influence of the biomass on the interfacial mass transfer can be partially counteracted by adding 1-octanol into the organic phase, improving the solvent’s ability to solve the fumaric acid–Amberlite LA-2 complex and simplifying the reactive extraction mechanism, effects that were found to be more important for low-polar solvents. Consequently, for the same mixing intensity, the maximum amplification factor was reached for n-heptane, its value being almost 5–6 times higher than that obtained for dichloromethane and over 2 times higher than that obtained with n-butyl acetate.
Applicability of Preliminary Standards for the Hanok Comfort Evaluation Based on Spatial Indices
Authors: Kim Jae-Hyang , Han Seung-Hoon
Published: October 2021

There is much discussion of the energy performance of buildings in order to carry out sustainable construction. However, buildings are not simply spaces that offer excellent energy performance, but are based on climate, culture, and context, which for sustainability are factors that also need to be considered. Hanok, a vernacular housing form in Korea, is based on organic characteristics and harmony between nature and human. Hanok aims to avoid the destruction of the surrounding ecosystem and to borrow the natural environment as a passive element. Wood, stone, clay lime and paper are mainly used as building materials. Therefore, hanok has a sustainable value that is different from its energy performance. In this context, it is necessary to analyze whether a hanok is a good space to live in, and a study on comfort performance was conducted. In this study, an analysis of the spatial comfort of Hanok was conducted. This research tried to derive performance indicators to pursue the spatial comfort of hanok that is mainly investigated through correlational analysis. The purpose of this study is, therefore, to find correlations by statistically analyzing user surveys and physical indicators, using Pearson correlation coefficient and regression analysis. This makes it possible to set preliminary standards for hanok comfort and how to consider these in the design stage.
Cyanobacteria as Valuable Tool in Biotechnology
Authors: Śliżewska Agnieszka , Żymańczyk-Duda Ewa
Published: October 2021

Cyanobacteria constitute an interesting group of photosynthetic microorganisms due to their morphological and genetic diversity that is related to their extremely long evolution process, which created the need for them to adapt to immensely heterogeneous environmental conditions. Cyanobacteria grow in salt and fresh waters as well as on the surface of soils and rocks. The diverse cell structure is characterized by the fact that they occur in many morphological forms, from small single cells through to larger ones as well as branches, threads, or spirals. Taking into account the presence of cyanobacteria in virtually all possible conditions and places on Earth, cyanobacteria represent an unexplored potential that is worth investigating. This review presents the possibilities of using algae in chosen areas of biotechnology: e.g., as biocatalysts or in industries such as the pharmaceutical industry. It covers the characteristics of secondary metabolites along with their division and the potential of using them as sources of effective drugs for many diseases. It presents an overview of the possibilities of using cyanobacteria in biotransformation processes. These processes are of great importance in the case of, for example, the neutralization of municipal, industrial, or chemical waste, the amount of which is constantly growing every year, and they are also an easier and cheaper path to obtain chemical compounds.
The Influence of Si/Al Ratio on the Physicochemical and Catalytic Properties of MgO/ZSM-5 Catalyst in Transesterification Reaction of Rapeseed Oil
Authors: Szkudlarek Łukasz , Chałupka Karolina , Maniukiewicz Waldemar , Albińska Jadwiga , Szynkowska-Jóźwik Malgorzata I. , Mierczyński Paweł
Published: October 2021

This work presents the comparative physicochemical and catalytic studies of metal oxide MgO catalysts in a transesterification reaction. The influence of the Si/Al ratio in the catalytic material on their catalytic properties in the studied process was extensively evaluated. In addition, the effect of the type of zeolite ZSM-5 form on the catalytic reactivity of MgO based catalysts was investigated. In order to achieve the main goals of this work, a series of MgO/ZSM-5 catalysts were prepared via the impregnation method. Their physicochemical properties were studied using X-ray diffraction (XRD), BET, FTIR and TPD-CO2 methods. The highest activity in the studied process exhibited MgO catalyst supported on ZSM-5 characterized by the highest ratio between silica and alumina. The most active catalyst system in the transesterification reaction was 10% MgO/ZSM-5 (Si/Al = 280), which showed the highest value of higher fatty acid methyl esters (94.6%) and high yield of triglyceride conversion (92.9%). The high activity of this system is explained by the alkalinity, sorption properties in relation to methanol and its high specific surface area compared to the rest of the investigated MgO based catalysts.
Recent Progress of Metal Nanoparticle Catalysts for C–C Bond Forming Reactions
Authors: Ohtaka Atsushi
Published: October 2021

Over the past few decades, the use of transition metal nanoparticles (NPs) in catalysis has attracted much attention and their use in C–C bond forming reactions constitutes one of their most important applications. A huge variety of metal NPs, which have showed high catalytic activity for C–C bond forming reactions, have been developed up to now. Many kinds of stabilizers, such as inorganic materials, magnetically recoverable materials, porous materials, organic–inorganic composites, carbon materials, polymers, and surfactants have been utilized to develop metal NPs catalysts. This review classified and outlined the categories of metal NPs by the type of support.
Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease
Authors: Xue Rui , Su Lianyong , Lai Shengyi , Wang Yanyan , Zhao Derrick , Fan Jiangao , Chen Weidong , Hylemon Phillip B. , Zhou Huiping
Published: October 2021

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.
An Inducible System for Silencing Establishment Reveals a Stepwise Mechanism in Which Anchoring at the Nuclear Periphery Precedes Heterochromatin Formation
Authors: Loïodice Isabelle , Garnier Mickael , Nikolov Ivaylo , Taddei Angela
Published: October 2021

In eukaryotic cells, silent chromatin is mainly found at the nuclear periphery forming subnuclear compartments that favor silencing establishment. Here, we set up an inducible system to monitor silencing establishment at an ectopic locus in relation with its subnuclear localization in budding yeast. We previously showed that introducing LacI bound lacO arrays in proximity to gene flanked by HML silencers favors the recruitment of the yeast silencing complex SIR at this locus, leading to its silencing and anchoring at the nuclear periphery. Using an inducible version of this system, we show that silencing establishment is a stepwise process occurring over several cell cycles, with the progressive recruitment of the SIR complex. In contrast, we observed a rapid, SIR-independent perinuclear anchoring, induced by the high amount of LacI binding at the lacO array leading to nucleosome eviction at this array and to the phosphorylation of H2A in the neighboring nucleosomes by Mec1 kinase. While the initial phosphorylation of H2A (H2A-P) and perinuclear anchoring are independent of the SIR complex, its latter recruitment stabilizes H2A-P and reinforces the perinuclear anchoring. Finally, we showed that Sir3 spreading stabilizes nucleosomes and limits the access of specific DNA-binding protein to DNA.
GM101 in Combination with Histone Deacetylase Inhibitor Enhances Anti-Tumor Effects in Desmoplastic Microenvironment
Authors: Chang Han-Gyu , Choi Yong-Hyeon , Hong JinWoo , Choi Joung-Woo , Yoon A-Rum , Yun Chae-Ok
Published: October 2021

Oncolytic adenoviruses (oAds) have been evaluated in numerous clinical trials due to their promising attributes as cancer therapeutics. However, the therapeutic efficacy of oAds was limited due to variable coxsackie and adenovirus receptor (CAR) expression levels and the dense extracellular matrix (ECM) of heterogenic clinical tumors. To overcome these limitations, our present report investigated the therapeutic efficacy of combining GM101, an oAd with excellent tumor ECM degrading properties, and histone deacetylase inhibitor (HDACi). Four different HDACi (suberohydroxamic acid (SBHA), MS-275, trichostatin A (TSA), and valproic acid) candidates in combination with replication-incompetent and GFP-expressing Ad (dAd/GFP) revealed that SBHA and MS-275 exerted more potent enhancement in Ad transduction efficacy than TSA or valproic acid. Further characterization revealed that SBHA and MS-275 effectively upregulated CAR expression in cancer cells, improved the binding of Ad with cancer cell membranes, and led to dynamin 2- and clathrin-mediated endocytosis of Ad. The combination of GM101 with HDACi induced superior cancer cell killing effects compared to any of the monotherapies, without any additional cytotoxicity in normal cell lines. Further, GM101+SBHA and GM101+MS-275 induced more potent antitumor efficacy than any monotherapy in U343 xenograft tumor model. Potent antitumor efficacy was achieved via the combination of GM101 with HDACi, inducing necrotic and apoptotic cancer cell death, inhibiting cancer cell proliferation, degrading ECM in tumor tissue, and thus exerting the highest level of virus dispersion and accumulation. Collectively, these data demonstrate that the combination of GM101 and HDACi can enhance intratumoral dispersion and accumulation of oAd through multifaced mechanisms, making it a promising strategy to address the challenges toward successful clinical development of oAd.
Towards Splicing Therapy for Lysosomal Storage Disorders: Methylxanthines and Luteolin Ameliorate Splicing Defects in Aspartylglucosaminuria and Classic Late Infantile Neuronal Ceroid Lipofuscinosis
Authors: Banning Antje , Tikkanen Ritva
Published: October 2021

Splicing defects caused by mutations in the consensus sequences at the borders of introns and exons are common in human diseases. Such defects frequently result in a complete loss of function of the protein in question. Therapy approaches based on antisense oligonucleotides for specific gene mutations have been developed in the past, but they are very expensive and require invasive, life-long administration. Thus, modulation of splicing by means of small molecules is of great interest for the therapy of genetic diseases resulting from splice-site mutations. Using minigene approaches and patient cells, we here show that methylxanthine derivatives and the food-derived flavonoid luteolin are able to enhance the correct splicing of the AGA mRNA with a splice-site mutation c.128-2A>G in aspartylglucosaminuria, and result in increased AGA enzyme activity in patient cells. Furthermore, we also show that one of the most common disease causing TPP1 gene variants in classic late infantile neuronal ceroid lipofuscinosis may also be amenable to splicing modulation using similar substances. Therefore, our data suggest that splice-modulation with small molecules may be a valid therapy option for lysosomal storage disorders.
Functional Recellularization of Acellular Rat Liver Scaffold by Induced Pluripotent Stem Cells: Molecular Evidence for Wnt/B-Catenin Upregulation
Authors: Ebrahim Nesrine , Badr Omnia A. M. , Yousef Mohamed M. , Hassouna Amira , Sabry Dina , Farid Ayman Samir , Mostafa Ola , Saihati Hajir A. Al , Seleem Yasmin , Abd El Aziz Eman , Khalil Ahmed Hassan , Nawar Ahmed , Shoulah Ahmed A. , Aljasir Mohammad , Mohamed Amira Zaki , El-Sherbiny Mohamed , Elsherbiny Nehal M. , Eladl Mohamed Ahmed , Forsyth Nicholas Robert , Salim Rabab F.
Published: October 2021

Background. Liver transplantation remains the only viable therapy for liver failure but has a severely restricted utility. Here, we aimed to decellularize rat livers to form acellular 3D bio-scaffolds suitable for seeding with induced pluripotent cells (iPSCs) as a tool to investigate the role of Wnt/β-catenin signaling in liver development and generation. Methods. Dissected rat livers were randomly divided into three groups: I (control); II (decellularized scaffolds) and III (recellularized scaffolds). Liver decellularization was established via an adapted perfusion procedure and assessed through the measurement of extracellular matrix (ECM) proteins and DNA content. Liver recellularization was assessed through histological examination and measurement of transcript levels of Wnt/β-catenin pathway, hepatogenesis, liver-specific microRNAs and growth factors essential for liver development. Adult rat liver decellularization was confirmed by the maintenance of ECM proteins and persistence of growth factors essential for liver regeneration. Results. iPSCs seeded rat decellularized livers displayed upregulated transcript expression of Wnt/β-catenin pathway-related, growth factors, and liver specification genes. Further, recellularized livers displayed restored liver-specific functions including albumin secretion and urea synthesis. Conclusion. This establishes proof-of-principle for the generation of three-dimensional liver organ scaffolds as grafts and functional re-establishment.
Modulation of Immune Components on Stem Cell and Dormancy in Cancer
Authors: Jiang Xiaofan , Liang Lu , Chen Guanglei , Liu Caigang
Published: October 2021

Cancer stem cells (CSCs) refer to a certain subpopulation within the tumor entity that is characterized by restricted cellular proliferation and multipotent differentiation potency. The existence of CSCs has been proven to contribute to the heterogeneity of malignancies, accounting for intensified tumorigenesis, treatment resistance, and metastatic spread. Dormancy was proposed as a reversible state of cancer cells that are temporarily arrested in the cell cycle, possessing several hallmarks that facilitate their survival within a devastating niche. This transient period is evoked to enter an actively proliferating state by multiple regulatory alterations, and one of the most significant and complex factors comes from local and systemic inflammatory reactions and immune components. Although CSCs and dormant cancer cells share several similarities, the clear relationship between these two concepts remains unclear. Thus, the detailed mechanism of immune cells interacting with CSCs and dormant cancer cells also warrants elucidation for prevention of cancer relapse and metastasis. In this review, we summarize recent findings and prospective studies on CSCs and cancer dormancy to conclude the relationship between these two concepts. Furthermore, we aim to outline the mechanism of immune components in interfering with CSCs and dormant cancer cells to provide a theoretical basis for the prevention of relapse and metastasis.
The Cytotoxicity and Clearance of Mutant Huntingtin and Other Misfolded Proteins
Authors: Folger Austin , Wang Yanchang
Published: October 2021

Protein misfolding and aggregation are implicated in many neurodegenerative diseases. One of these diseases is Huntington’s, which is caused by increased glutamine-encoding trinucleotide repeats within the Huntingtin gene. Like other misfolded proteins, mutated Huntingtin proteins with polyglutamine expansions are prone to aggregation. Misfolded proteins exist as soluble monomers, small aggregates, or as large insoluble inclusion bodies. Misfolded protein aggregates are believed to be cytotoxic by stressing the protein degradation machinery, disrupting membrane structure, or sequestering other proteins. We recently showed that expression of misfolded proteins lowers cellular free ubiquitin levels, which compromises the protein degradation machinery. Therefore, the efficient degradation of misfolded proteins is critical to preserve cell health. Cells employ two major mechanisms to degrade misfolded proteins. The first is the ubiquitin-proteasome system (UPS), which ubiquitinates and degrades misfolded proteins with the assistance of segregase Cdc48/p97. The UPS pathway is mainly responsible for the clearance of misfolded proteins present as monomers or smaller aggregates. The second pathway is macroautophagy/autophagy, in which protein aggregates or inclusion bodies are recruited into an autophagosome before transport to the vacuole/lysosome for degradation. This review is focused on the current understanding of the cytotoxicity of misfolded proteins as well as their clearance pathways, with a particular emphasis on mutant Huntingtin.
Methanol–Water Purification Control Using Multi-Loop PI Controllers Based on Linear Set Point and Disturbance Models
Authors: Wahid Abdul , Rikimata Monica
Published: October 2021

Dimethyl ether (DME), derived from methanol, has been issued as an alternative to diesel and LPG. This study will continue the research of an optimized process control design for DME purification plants, specifically the methanol purification process. This way, water can be separated, and the main product, methanol, can be recycled for DME synthesis. A setpoint-based linear model of a methanol–water purification system has been developed with four controlled variables (CV) with objectives to; maintain a separated liquid water stream in the bottom stage (Stage 30) of the distillation column for methanol–water separation at 11.22%, keep the purified liquid methanol at a condenser at 58.81 °C and 49.96% of level, and the last CV is the cooler in the distillate stream, to keep the purified methanol’s top product at 40.75 °C. To complete the model, a first order plus dead time (FOPDT) disturbance model is created against the inlet temperature and flow rate of the feed, the major cause of disturbances in the industry. Using a traditional proportional integral controller connected to each controlled variable, a multi-loop control system is formed with optimization and compared to the disturbance rejection of multivariable model predictive control (MMPC). The final improvement against the feed temperature and flow for CV1, CV2, CV3, and CV4 is shown by, respectively, Integral Absolute Error (IAE) values of 79.49%, 99.90%, 100%, and 99.99% and Integral Square Error (ISE) values of 97.1%, 100%, 99.99%, and 100%.
Genome-Wide Identification of LRR-RLK Family in Saccharum and Expression Analysis in Response to Biotic and Abiotic Stress
Authors: Cheng Wei , Wang Zhoutao , Xu Fu , Ahmad Waqar , Lu Guilong , Su Yachun , Xu Liping
Published: October 2021

The leucine-rich repeat receptor-like protein kinase (LRR-RLK) gene family is the largest family of the receptor-like protein kinases (RLKs) superfamily in higher plants, which is involved in regulating the plant growth and development, stress responses, signal transduction and so on. However, no comprehensive analyses of LRR-RLKs have been reported in sugarcane. Here, we performed a comprehensive analysis of the LRR-RLK gene family in sugarcane ancestor species Saccharum spontaneum. A total of 437 LRR-RLK genes were identified and categorized into 14 groups based on a maximum likelihood phylogenetic tree. The chromosome location showed an uneven distribution on all 32 chromosomes in sugarcane. Subsequently, the exon–intron organization structure and conserved motif arrangement were relatively conserved among the same groups or subgroups and between Arabidopsis and S. spontaneum genomes. Furthermore, the promoter sequences analyses showed that sugarcane LRR-RLK genes (SsLRR-RLKs) were strongly regulated by various environmental stimuli, phytohormonal factors and transcription factors (TFs). Eventually, the expression profiles of SsLRR-RLK genes at different stresses were analyzed based on RNA-seq data, suggesting their potential roles in the regulation of sugarcane responses to diverse abiotic and biotic stress. Overall, the findings provide insight into the potential functional roles and lay the foundation for further functional study.
Efficiency of Application of (Mo, Al)N-Based Coatings with Inclusion of Ti, Zr or Cr during the Turning of Steel of Nickel-Based Alloy
Authors: Vereschaka Alexey , Milovich Filipp , Andreev Nikolay , Sitnikov Nikolay , Alexandrov Islam , Muranov Alexander , Mikhailov Maxim , Tatarkanov Aslan
Published: October 2021

The article compares the properties of multilayer composite wear-resistant coatings of Zr–ZrN–(Zr, Mo, Al)N, Ti–TiN–(Ti, Mo, Al)N, and Cr–CrN–(Cr, Mo, Al)N. The investigation was focused on hardness, resistance to fracture during scratch tests, elemental composition, and structure of the coatings. Experiments were carried out to study the wear resistance of coated carbide tools during the turning of 1045 steel and of NiCr20TiAl heat-resistant nickel alloy. With the elemental compositions identical in the content of molybdenum (Mo) and aluminium (Al), identical thicknesses and nanolayer periods of λ, the coatings being studied demonstrated a noticeable difference in wear resistance. Both during the turning of steel and nickel-based alloy, the highest wear resistance was detected for tools with the Zr–ZrN–(Zr, Mo, Al)N coating (the tool life was 3–5 times higher than for uncoated tools). The good wear resistance of the Zr–ZrN–(Zr, Mo, Al)N coating may be related to the optimal combination of hardness and plasticity and the active formation of molybdenum oxide (MoO3) on the coating surface during the cutting, with good tribological and protective properties.