bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiment-Based Synthetic Structural Analysis Combining Digital Image Processing and a Strong Form Meshfree Method
Authors: Park Junwon , Kim Kyeong-Hwan , Yoon Young-Cheol , Lee Sang-Ho
Published: November 2020

This paper presents an experiment-based synthetic structural analysis method that combines digital image processing (DIP) and the particle difference method (PDM), which is a strong form-based meshfree method. The proposed method uses images to determine the displacement of deformed specimens, interpolates the displacement onto nodes of the PDM model without meshes or grids, and calculates the kinematic variables. Furthermore, the pixel extraction method for the target area and the method of setting the region of interest for expediting DIP were used during the synthetic structural analysis. A method for effectively expanding the number of tracking points and an improved method for labeling tracking points are also presented. To verify the performance of the analysis, the experimental and numerical analysis results of a three-point bending test on a rubber beam were compared in terms of various mechanical variables as well as with the PDM results of a simulated bending test. It was found that tracking point expansion and adjusting the radius of the domain of influence are advantageous for performing an accurate calculation without losing computational efficiency. It was demonstrated that the synthetic structural analysis effectively overcomes the shortcomings of the conventional experiments and the limitations of pure simulations.
The Oral Microbiome in Children with Black Stained Tooth
Authors: Hwang Ji Young , Lee Hyo-Seol , Choi Jaehyuk , Nam Ok Hyung , Kim Mi Sun , Choi Sung Chul
Published: November 2020

Black stain (BS) is a characteristic extrinsic discoloration, which occurs along the third cervical line of the buccal and/or lingual surfaces of teeth, particularly in the primary dentition of humans. BS is produced by oral bacteria and byproducts of saliva, but there is a controversy about related bacteria. The aim of this study was to identify the oral microbiome in tooth BS using pyrosequencing. It was hypothesized that the oral microbiome of BS in children might be related to black-pigment producing bacteria. Supragingival dental plaque was obtained from six children (mean 8.1 years) with BS and four children (mean 8.3 years) without BS. The bacterial metagenome was obtained by pyrosequencing. The BS group contained 348 operative taxonomic units (OTUs), whereas the control group had 293 OTUs. Microbial abundance and diversity were significantly higher in the BS group (p < 0.05). In the heatmap, the correlation between samples was the same as the BS scale. At the genus level, six genera—Abiotrophia, Eikenella, Granulicatella, Neisseria, Porphyromonas and Streptococcus—were significantly different between the two groups (p < 0.05). We suggested that compositional changes in the oral microbiome are essential, and several species in the genus Neisseria, Porphyromonas and Streptococcus may be major contributors for BS formation. Although the number of subjects was relatively limited, our study is the first species-level analysis of pyrosequencing data in BS formation.
Credibility Based Imbalance Boosting Method for Software Defect Proneness Prediction
Authors: Tong Haonan , Wang Shihai , Li Guangling
Published: November 2020

Imbalanced data are a major factor for degrading the performance of software defect models. Software defect dataset is imbalanced in nature, i.e., the number of non-defect-prone modules is far more than that of defect-prone ones, which results in the bias of classifiers on the majority class samples. In this paper, we propose a novel credibility-based imbalance boosting (CIB) method in order to address the class-imbalance problem in software defect proneness prediction. The method measures the credibility of synthetic samples based on their distribution by introducing a credit factor to every synthetic sample, and proposes a weight updating scheme to make the base classifiers focus on synthetic samples with high credibility and real samples. Experiments are performed on 11 NASA datasets and nine PROMISE datasets by comparing CIB with MAHAKIL, AdaC2, AdaBoost, SMOTE, RUS, No sampling method in terms of four performance measures, i.e., area under the curve (AUC), F1, AGF, and Matthews correlation coefficient (MCC). Wilcoxon sign-ranked test and Cliff’s δ are separately used to perform statistical test and calculate effect size. The experimental results show that CIB is a more promising alternative for addressing the class-imbalance problem in software defect-prone prediction as compared with previous methods.
Online Reinforcement Learning-Based Control of an Active Suspension System Using the Actor Critic Approach
Authors: Fares Ahmad , Bani Younes Ahmad
Published: November 2020

In this paper, a controller learns to adaptively control an active suspension system using reinforcement learning without prior knowledge of the environment. The Temporal Difference (TD) advantage actor critic algorithm is used with the appropriate reward function. The actor produces the actions, and the critic criticizes the actions taken based on the new state of the system. During the training process, a simple and uniform road profile is used while maintaining constant system parameters. The controller is tested using two road profiles: the first one is similar to the one used during the training, while the other one is bumpy with an extended range. The performance of the controller is compared with the Linear Quadratic Regulator (LQR) and optimum Proportional-Integral-Derivative (PID), and the adaptiveness is tested by estimating some of the system’s parameters using the Recursive Least Squares method (RLS). The results show that the controller outperforms the LQR in terms of the lower overshoot and the PID in terms of reducing the acceleration.
P-Wave Reflection Approximation of a Thin Bed and Its Application
Authors: Yang Chun , Wang Yun , Xiong Shu , Li Zikun , Han Hewei
Published: November 2020

“Thin-bed” reservoirs have become important targets of seismic exploration and exploitation. However, traditional amplitude versus offset/amplitude versus angle (AVO/AVA) technologies, for example, those based on Zoeppritz equations and their approximations for a single interface, are not sufficiently accurate for thin-bed stratigraphy. Analytic solutions of thin-bed reflectivity may become practical for thin-bed AVO analysis and inversion. Therefore, a linear analytic approximation of thin-bed P-wave reflectivity is developed under small-incidence and thin-bed assumptions. Numerical simulations show that the amplitude approximation errors are usually smaller than 10% for incidence angles less than 20 degrees, and the thin-bed thicknesses are less than one-tenth of the P-wave wavelength. Based on the least-squares approach, the inversion strategy is proposed using the approximate formula. A synthetic data test shows that the proposed inversion method can produce more accurate thin-bed properties than that based on the Zoeppritz equations, which reveals the potential of the inversion method based on the linear analytic approximate formula in the fine characterization of thin reservoirs.
Fault Diagnosis of Planet Gear Using Continuous Vibration Separation and Minimum Entropy Deconvolution
Authors: Shen Jian , Zhang Lun , Hu Niaoqing
Published: November 2020

Planet gear is the most unique dynamic component in planetary gearbox. It rotates around sun gear while rotating around its own central axis, causing modulation effect in monitoring signal. Planetary gear is usually connected to heavy external loads and other transmissions, fault feature of planet gear may be overwhelmed by noises and other signals. Focused on planet gear inside planetary gearbox, a method for fault diagnosis is proposed in this paper based on continuous vibration separation (CVS) and minimum entropy deconvolution (MED). In this method, CVS is designed to separate dynamic responses of planet gear from overall vibration responses of planetary gearbox by overcoming the modulation effect and depressing noises. MED is used for enhancement detection of fault-related impulses. Simulations and experiments are conducted to collect signals for analysis. The proposed method is also compared with vibration separation method (VS). Both simulation and experiment analysis indicate that the proposed planet gear fault diagnosis method is effective. Comparative study indicates that CVS-MED method improves VS by keeping signal periodicity while overcoming modulation effect and depressing noises.
Design and Evaluation of a System for Decentralized Management of Solidarity Actions during the COVID-19 Crisis
Authors: Albusac J. , Castro-Schez J. J. , Castro-Garcia M. , Perez-Flores J. C. , Canales-Vazquez J.
Published: November 2020

Since the start of the COVID-19 pandemic, the top priority was to hinder the spread of the virus and prevent the collapse of the health systems. To achieve this, it was mandatory to ensure adequate supplies of personal protective equipment (PPE), which may not have been available in the short-term during the first months of the crisis. While leading manufacturing companies all over the world were retooling their factories to produce medical equipment, 3D printing offered a transition solution to quickly supply PPEs in the case of emergency. In this context, the University of Castilla-La Mancha started a new solidarity project to produce PPEs via 3D printing, especially for healthcare staff. This project was characterized by the commitment of several geographically distributed volunteers, with limitations due to confinement. The group of volunteers required an organizational model supported by ad-hoc technology to make their collaboration efficient. This article demonstrates how a centralized production model is not efficient in such a situation, and proposes a novel web system supported by an intelligent recommender, which facilitates a distributed organizational model that optimizes manufacturing and delivery times of PPEs. The results show how our proposal drastically improves the efficiency of the group of collaborators, and adequately address the high social demand concentrated in a short period. This was a crucial change for the production and distribution of over 23,500 PPEs during the first 40 days of the crisis, in one of the regions with a higher rate of COVID-19 cases in Europe.
Simulation of Chronic Intoxication in Rats Exposed to Cadmium and Mercury
Authors: Cimboláková Iveta , Kimáková Tatiana , Pavolová Henrieta , Bakalár Tomáš , Kudelas Dušan , Seňová Andrea
Published: November 2020

Cadmium and mercury are widespread and non-biodegradable pollutants of great concern to human and animal health. In this study, the influence of exposure to low doses of cadmium and mercury on Wistar rats was investigated. The experiments aimed to identify suitable markers of chronic intoxication with heavy metals in rats. The subjects were 48 naive young rats (24 females and 24 males), four weeks old, grouped randomly into three distinct groups—control group, group exposed to cadmium and group exposed to mercury. The control group received sham treatment—clean untreated water. Cd exposed group received water containing cadmium chloride dihydrate and Hg exposed group received water with mercury dichloride. Both cadmium and mercury were administered to experimental rats in drinking water in concentrations exceeding the maximum acceptable concentration of these metals 500 times, i.e., 0.5 mg Hg and 2.5 mg Cd per liter of water. The results were evaluated quarterly during the experiment (52 weeks). Selected physiological parameters (life span, body weight changes and intake of food and water), reproductive parameters (number of births (litters), number of born pups and number of raised pups) and toxicological parameters (average daily dose, total dose received and the amount of toxic metal received) were studied. The results of the experiments indicate differences between both individual groups and between males and females, which confirmed that these parameters are essential in such experiments of chronic exposure to subtoxic doses of heavy metals.
Systematic Innovation Based BPR Regime—A Factors Analysis
Authors: Jehan Shahzadah Nayyar , Elapatha Vishakha Wijeratne
Published: November 2020

Sri Lankan public services have a lingering colonial legacy, and there have been several efforts since the country’s independence to break away from the restraints of the past to align them with modern times and expectations. The drive for modernization of public services passed through several phases of experimentation without much success in the past. A significant attempt at the modernization of public services was made in the first decade of this millennium; we now notice substantial changes in public service delivery (PSD) in the country. In this paper, we assess the impact of an inside-outside-inside (IOI)-based open system innovation-related business process reengineering (BPR) regime adapted for reforms in the organization and the delivery of public services in the country. We carried out an input and output analysis of the BPR regime, adopted by various departments and ministries of the government of Sri Lanka to improve the PSD infrastructure. A broad-based ground survey on a five-point Likert scale was carried out, and performance data were collected. We collected a total of 290 responses—each questionnaire was composed of 40 questions regarding the inputs and the outputs of the regime’s implementation. Applying an ordered multivariate logistic regression model, we have attempted to estimate correlations amongst inputs, results, and overall perception of success or failure of the BPR regime across 29 departments and ministries (D&M). We have tabulated summary statistics and regression results to assess the relative significance of various regime inputs and their impact on the corresponding outcomes. The outcomes suggest that while all inputs and outputs are significantly correlated, some inputs have a more significant effect on the results expected from the BPR regime. We have used original data acquired through a survey carried out directly through the PSD organizations in the country, and this study is the first of its kind in this regard. We expect this study will be of high utility to the personnel engaged in the planning and implementation of PSD through systematic innovation and BPR, not only in Sri Lanka but also for many other professionals and researchers who are engaged in designing and execution of similar service improvements and reengineering strategies in different countries around the world.
The Impact of Decarbonization Scenarios on Air Quality and Human Health in Poland—Analysis of Scenarios up to 2050
Authors: Zyśk Janusz , Wyrwa Artur , Suwała Wojciech , Pluta Marcin , Olkuski Tadeusz , Raczyński Maciej
Published: November 2020

Poland faces two great challenges in the field of environment and atmosphere protection: improving air quality, especially by reducing particulate matter (PM) emissions, and reducing relatively high greenhouse gas emissions. The aim of this research was to investigate how the fuel and technological transformations in the power, road transport, and household and tertiary sectors aimed at reducing carbon dioxide (CO2) emissions in Poland would affect air quality, human health, and the associated external costs. The study was conducted for 2050 while considering 2015 as the base year. Ambient PM2.5 (particles with a diameter of less than 2.5 µm) concentration was used as a proxy air quality indicator. The analysis was based on decarbonization scenarios developed within the REFLEX Project (Analysis of the European energy system under the aspects of flexibility and technological progress). The three scenarios of the REFLEX Project focused on the reduction of CO2 emissions up to 2050 from various sectors, mainly by the means of fuel and technological switches. This also led to the changes in the emission levels of pollutants that directly affect air quality, which were calculated with the use of fuel- and technology-specific emission factors. Next, for each emission scenario, ambient concentrations of PM2.5 and others pollutants were calculated with the use of the Polyphemus—an Eulerian-type air quality modelling system. Subsequently, the health impact of population exposed to air pollution and associated external costs were calculated using the πESA (Platform for Integrated Energy System Analysis) platform. The health impacts considered were the number of years of life lost, restricted activity days, and number of chronic bronchitis cases. The results showed that the largest reductions in both greenhouse gas and PM emissions—and consequently improvements of air quality resulting in a decrease of negative impacts on human health and a decrease of external costs—can be achieved by the transformation of heat production in the household and tertiary sector. The results also showed that the decrease in PM2.5 emissions envisaged in the analyzed scenarios in 2050 will lead to a reduction in the number of lost years of life by about 35 thousand and an avoidance of external costs by EUR 2.4 billion.
Regularization Method for Singularly Perturbed Integro-Differential Equations with Rapidly Oscillating Coefficients and Rapidly Changing Kernels
Authors: Kalimbetov Burkhan , Safonov Valeriy
Published: November 2020

In this paper, we consider a system with rapidly oscillating coefficients, which includes an integral operator with an exponentially varying kernel. The main goal of the work is to develop an algorithm for the regularization method for such systems and to identify the influence of the integral term on the asymptotic behavior of the solution of the original problem.
Deficiency of Splicing Factor 1 (SF1) Reduces Intestinal Polyp Incidence in ApcMin/+ Mice
Authors: Godavarthi Jyotsna D. , Polk Shahrazad , Nunez Lisa , Shivachar Amruthesh , Glenn Griesinger Nancy L. , Matin Angabin
Published: November 2020

Background: Splicing factor 1 (SF1) is a conserved alternative splicing factor expressed in many different mammalian cell types. The genetically modified Sf1+/− (or Sf1β-geo/+) mice express reduced levels of SF1 protein in mouse tissues, including in cells of the intestines. Mutational inactivation of human adenomatous polyposis coli (APC) gene deregulates the Wnt signaling pathway and is a frequent genetic event in colon cancers. Mice with a point mutation in the Apc gene (ApcMin/+) also develop numerous intestinal polyps at a young age. Our aim was to determine the effect of reduced SF1 levels on polyp development due to the strong driver ApcMin/+ mutation. Methods: We utilized mice genetically deficient for expression of SF1 to assess how SF1 levels affect intestinal tumorigenesis. We crossed ApcMin/+ to Sf1+/− mice to generate a cohort of heterozygous mutant ApcMin/+;Sf1+/− mice and compared intestinal polyp development in these mice to that in a control cohort of sibling ApcMin/+ mice. We compared total polyp numbers, sizes of polyps and gender differences in polyp numbers between ApcMin/+;Sf1+/− and ApcMin/+ mice. Results: Our results showed that ApcMin/+ mice with lower SF1 expression developed 25–30% fewer intestinal polyps compared to their ApcMin/+ siblings with normal SF1 levels. Interestingly, this difference was most significant for females (ApcMin/+;Sf1+/− and ApcMin/+ females developed 39 and 55 median number of polyps, respectively). Furthermore, the difference in polyp numbers between ApcMin/+;Sf1+/− and ApcMin/+ mice was significant for smaller polyps with a size of 2 mm or less, whereas both groups developed similar numbers of larger polyps. Conclusions: Our results suggest that lower SF1 levels likely inhibit the rate of initiation of polyp development due to ApcMin/+ driver mutation in the mouse intestine. Thus, therapeutic lowering of SF1 levels in the intestine could attenuate intestinal polyp development.
Development of the Biomechanical Technologies for the Modeling of Major Segments of the Human Body: Linking the Past with the Present
Authors: Cicchella Antonio
Published: November 2020

The knowledge of human body proportions and segmental properties of limbs, head and trunk is of fundamental importance in biomechanical research. Given that many methods are employed, it is important to know which ones are currently available, which data on human body masses, lengths, center of mass (COM) location, weights and moment of inertia (MOI) are available and which methods are most suitable for specific research purposes. Graphical, optical, x-ray and derived techniques, MRI, laser, thermography, has been employed for in-vivo measurement, while direct measurements involve cadaveric studies with dissection and various methods of acquiring shape and size of body segments. The present review examines the literature concerning human body segments’ properties for biomechanical purposes starting with a historical examination. It emerges that data obtained in studies on cadaveric specimens are still accurate in comparison to more recent technologies, whilst technological tools currently available are manifolds, each one with proper advantages and disadvantages. Classical studies were focused mainly on white men, while in recent years, the available data on body segments have been extended to children, women, and other races. Additionally, data on special populations (obese, pregnant women) are starting to appear in the scientific literature.
Probing Membrane Protein Assembly into Nanodiscs by In Situ Dynamic Light Scattering: A2A Receptor as a Case Study
Authors: Reis Rosana I. , Moraes Isabel
Published: November 2020

Membrane proteins play a crucial role in cell physiology by participating in a variety of essential processes such as transport, signal transduction and cell communication. Hence, understanding their structure–function relationship is vital for the improvement of therapeutic treatments. Over the last decade, based on the development of detergents, amphipoles and styrene maleic-acid lipid particles (SMALPs), remarkable accomplishments have been made in the field of membrane protein structural biology. Nevertheless, there are still many drawbacks associated with protein–detergent complexes, depending on the protein in study or experimental application. Recently, newly developed membrane mimetic systems have become very popular for allowing a structural and functional characterisation of membrane proteins in vitro. The nanodisc technology is one such valuable tool, which provides a more native-like membrane environment than detergent micelles or liposomes. In addition, it is also compatible with many biophysical and biochemical methods. Here we describe the use of in situ dynamic light scattering to accurately and rapidly probe membrane proteins’ reconstitution into nanodiscs. The adenosine type 2A receptor (A2AR) was used as a case study.
Deciphering the Role of Positions 145 and 165 in Fluorescence Lifetime Shortening in the EGFP Variants
Authors: Mamontova Anastasia V. , Shakhov Aleksander M. , Lukyanov Konstantin A. , Bogdanov Alexey M.
Published: November 2020

The bright ultimately short lifetime enhanced emitter (BrUSLEE) green fluorescent protein, which differs from the enhanced green fluorescent protein (EGFP) in three mutations, exhibits an extremely short fluorescence lifetime at a relatively high brightness. An important contribution to shortening the BrUSLEE fluorescence lifetime compared to EGFP is provided by the T65G substitution of chromophore-forming residue and the Y145M mutation touching the chromophore environment. Although the influence of the T65G mutation was studied previously, the role of the 145th position in determining the GFPs physicochemical characteristics remains unclear. In this work, we show that the Y145M substitution, both alone and in combination with the F165Y mutation, does not shorten the fluorescence lifetime of EGFP-derived mutants. Thus, the unlocking of Y145M as an important determinant of lifetime tuning is possible only cooperatively with mutations at position 65. We also show here that the introduction of a T65G substitution into EGFP causes complex photobehavior of the respective mutants in the lifetime domain, namely, the appearance of two fluorescent states with different lifetimes, preserved in any combination with the Y145M and F165Y substitutions.
Effect of a Bio-Based Dispersing Aid (Einar® 101) on PLA-Arbocel® Biocomposites: Evaluation of the Interfacial Shear Stress on the Final Mechanical Properties
Authors: Aliotta Laura , Gigante Vito , Cinelli Patrizia , Coltelli Maria-Beatrice , Lazzeri Andrea
Published: November 2020

In this paper, the production and the characterization of poly (lactic) acid (PLA)-based composites containing different amounts (from 10 wt.% to 25 wt.%) of ultra-short cellulose fibers (Arbocel 600 BE/PU) have been investigated. On the basis of a previous study, it was observed that the addition of the cellulose fibers led to an embrittlement of the composite. Consequently, in order to obtain a composite with enhanced impact resistance and elongation at break, the effect of the Einar 101 addition (a bio-based dispersing aid additive) was analyzed. The role of the adhesion between the fiber and the matrix, coupled with a better fiber dispersion, was thus evaluated. Also, the consequences on the final mechanical properties (tensile and impact test) caused by the Einar addition were investigated. Analytical models were also applied in order to obtain an evaluation of the variation of the interfacial shear stress (IFSS) (strictly correlated to the fiber-matrix adhesion) caused by the Einar introduction. Furthermore, due to the very low aspect ratio of the Arbocel fibers, a suitable Bader and Boyer model variation was adopted in order to have a better quantitative estimation of the IFSS value.
Ferroptosis in Friedreich’s Ataxia: A Metal-Induced Neurodegenerative Disease
Authors: La Rosa Piergiorgio , Petrillo Sara , Fiorenza Maria Teresa , Bertini Enrico Silvio , Piemonte Fiorella
Published: November 2020

Ferroptosis is an iron-dependent form of regulated cell death, arising from the accumulation of lipid-based reactive oxygen species when glutathione-dependent repair systems are compromised. Lipid peroxidation, mitochondrial impairment and iron dyshomeostasis are the hallmark of ferroptosis, which is emerging as a crucial player in neurodegeneration. This review provides an analysis of the most recent advances in ferroptosis, with a special focus on Friedreich’s Ataxia (FA), the most common autosomal recessive neurodegenerative disease, caused by reduced levels of frataxin, a mitochondrial protein involved in iron–sulfur cluster synthesis and antioxidant defenses. The hypothesis is that the iron-induced oxidative damage accumulates over time in FA, lowering the ferroptosis threshold and leading to neuronal cell death and, at last, to cardiac failure. The use of anti-ferroptosis drugs combined with treatments able to activate the antioxidant response will be of paramount importance in FA therapy, such as in many other neurodegenerative diseases triggered by oxidative stress.
Self-Assembling β-Glucan Nanomedicine for the Delivery of siRNA
Authors: Lee Kyungwoo , Min Daejin , Choi Yonghyun , Yoon Semi , Jang Jaehee , Hwang Jangsun , Jeon Hojeong , Cho Yong Woo , Choi Jonghoon
Published: November 2020

We aimed to design and manufacture a transporter capable of delivering small interfering RNAs (siRNAs) into the skin without causing any damage. β-glucans are unique chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability. However, the chiral properties of these polymers have hardly been applied in drug delivery systems. In this study, β-glucan nanoparticles were designed and manufactured to deliver genetic material to the target cells. The β-glucan molecules were self-assembled with an siRNA into nanoparticles of 300–400 nm in diameter via a conformational transition process, in order to construct a gene delivery system. The assembled gene nanocarriers were associated with high gene-loading ability. The expression and efficiency of siRNA were verified after its delivery via β-glucan. Our results provide evidence that β-glucan nanoparticles can be effectively used to deliver siRNA into the cells.
SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma
Authors: Lee Jang-Seok , Kim Hee Yeon , Won Bomyi , Kang Sang Won , Kim Yong-Nyun , Jang Hyonchol
Published: November 2020

Many lung cancer deaths result from relapses in distant organs, such as the brain or bones, after standard chemotherapy. For cancer cells to spread to other organs, they must survive as circulating tumor cells (CTCs) in blood vessels. Thus, reducing distant recurrence after chemotherapy requires simultaneously inhibiting drug resistance and CTC survival. Here, we investigated the molecular pathways and genes that are commonly altered in drug-resistant lung cancer cells and lung tumor spheroid (TS) cells. First, RNA sequencing was performed in drug-resistant cells and TS cells originating from H460 and A549 lung cancer cells. Bioinformatic pathway analysis showed that cell cycle-related pathways were downregulated in drug-resistant cells, and cholesterol biosynthesis-related pathways were upregulated in TS cells. Seizure-related 6 homolog-like 2 (SEZ6L2) was selected as a gene that was commonly upregulated in both drug-resistant cells and TS cells, and that showed elevated expression in samples from lung adenocarcinoma patients. Second, the protein expression of SEZ6L2 was analyzed by flow cytometry. The proportions of SEZ6L2 positive cells among both drug-resistant cells and TS cells was increased. Finally, as SEZ6L2 is a transmembrane protein with an extracellular region, the function of SEZ6L2 was disrupted by treatment with an anti-SEZ6L2 antibody. Treatment with the anti-SEZ6L2 antibody reduced drug resistance and TS formation. Overall, our data showed that SEZ6L2 plays an important role in drug resistance and TS formation and may be a therapeutic target for reducing distant recurrence of lung adenocarcinoma.
Emerging Neurological and Psychobiological Aspects of COVID-19 Infection
Authors: Tancheva Lyubka , Petralia Maria Cristina , Miteva Simona , Dragomanova Stela , Solak Ayten , Kalfin Reni , Lazarova Maria , Yarkov Dobri , Ciurleo Rosella , Cavalli Eugenio , Bramanti Alessia , Nicoletti Ferdinando
Published: November 2020

The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million people. The spectrum of clinical manifestations observed during COVID-19 infection varies from asymptomatic to critical life-threatening clinical conditions. Emerging evidence shows that COVID-19 affects far more organs than just the respiratory system, including the heart, kidneys, blood vessels, liver, as well as the central nervous system (CNS) and the peripheral nervous system (PNS). It is also becoming clear that the neurological and psychological disturbances that occur during the acute phase of the infection may persist well beyond the recovery. The aim of this review is to propel further this emerging and relevant field of research related to the pathophysiology of neurological manifestation of COVID-19 infection (Neuro-COVID). We will summarize the PNS and CNS symptoms experienced by people with COVID-19 both during infection and in the recovery phase. Diagnostic and pharmacological findings in this field of study are strongly warranted to address the neurological and psychological symptoms of COVID-19.
Strategy-Specific Patterns of Arc Expression in the Retrosplenial Cortex and Hippocampus during T-Maze Learning in Rats
Authors: Czajkowski Rafał , Zglinicki Bartosz , Rejmak Emilia , Konopka Witold
Published: November 2020

The retrosplenial cortex (RSC) belongs to the spatial memory circuit, but the precise timeline of its involvement and the relation to hippocampal activation have not been sufficiently described. We trained rats in a modified version of the T maze with transparent walls and distant visual cues to induce the formation of allocentric spatial memory. We used two distinct salient contexts associated with opposite sequences of turns. Switching between contexts allowed us to test the ability of animals to utilize spatial information. We then applied a CatFISH approach with a probe directed against the Arc immediate early gene in order to visualize the associated memory engrams in the RSC and the hippocampus. After training, rats displayed two strategies to solve the maze, with half of the animals relying on distant spatial cues (allocentric) and the other half using egocentric strategy. Rats that did not utilize the spatial cues showed higher Arc levels in the RSC compared to the allocentric group. The overlap between the two context engrams in the RSC was similar in both groups. These results show differential involvement of the RSC and hippocampus during spatial memory acquisition and point toward their distinct roles in forming the cognitive maps.
Amygdala Low-Frequency Stimulation Reduces Pathological Phase-Amplitude Coupling in the Pilocarpine Model of Epilepsy
Authors: Mihály István , Orbán-Kis Károly , Gáll Zsolt , Berki Ádám-József , Bod Réka-Barbara , Szilágyi Tibor
Published: November 2020

Temporal-lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and warrants the development of new therapies, such as deep-brain stimulation (DBS). DBS was applied to different brain regions for patients with epilepsy; however, the mechanisms of action are not fully understood. Therefore, we tried to characterize the effect of amygdala DBS on hippocampal electrical activity in the lithium-pilocarpine model in male Wistar rats. After status epilepticus (SE) induction, seizure patterns were determined based on continuous video recordings. Recording electrodes were inserted in the left and right hippocampus and a stimulating electrode in the left basolateral amygdala of both Pilo and age-matched control rats 10 weeks after SE. Daily stimulation protocol consisted of 4 × 50 s stimulation trains (4-Hz, regular interpulse interval) for 10 days. The hippocampal electroencephalogram was analyzed offline: interictal epileptiform discharge (IED) frequency, spectral analysis, and phase-amplitude coupling (PAC) between delta band and higher frequencies were measured. We found that the seizure rate and duration decreased (by 23% and 26.5%) and the decrease in seizure rate correlated negatively with the IED frequency. PAC was elevated in epileptic animals and DBS reduced the pathologically increased PAC and increased the average theta power (25.9% ± 1.1 vs. 30.3% ± 1.1; p < 0.01). Increasing theta power and reducing the PAC could be two possible mechanisms by which DBS may exhibit its antiepileptic effect in TLE; moreover, they could be used to monitor effectiveness of stimulation.
Time to Renovate the Humor Styles Questionnaire? An Item Response Theory Analysis of the HSQ
Authors: Silvia Paul J. , Rodriguez Rebekah M.
Published: November 2020

The Humor Styles Questionnaire (HSQ) is one of the most popular self-report scales in humor research. The present research conducted a forward-looking psychometric analysis grounded in Rasch and item response theory models, which have not been applied to the HSQ thus far. Regarding strengths, the analyses found very good evidence for reliability and dimensionality and essentially zero gender-based differential item functioning, indicating no gender bias in the items. Regarding opportunities for future development, the analyses suggested that (1) the seven-point rating scale performs poorly relative to a five-point scale; (2) the affiliative subscale is far too easy to endorse and much easier than the other subscales; (3) the four subscales show problematic variation in their readability and proportion of reverse-scored items; and (4) a handful of items with poor discrimination and high local dependence are easy targets for scale revision. Taken together, the findings suggest that the HSQ, as it nears the two-decade mark, has many strengths but would benefit from light remodeling.
BRCA in Gastrointestinal Cancers: Current Treatments and Future Perspectives
Authors: Molinaro Eleonora , Andrikou Kalliopi , Casadei-Gardini Andrea , Rovesti Giulia
Published: November 2020

A strong association between pancreatic cancer and BRCA1 and BRCA2 mutations is documented. Based on promising results of breast and ovarian cancers, several clinical trials with poly (ADP-ribose) polymerase inhibitors (PARPi) are ongoing for gastrointestinal (GI) malignancies, especially for pancreatic cancer. Indeed, the POLO trial results provide promising and awaited changes for the pancreatic cancer therapeutic landscape. Contrariwise, for other gastrointestinal tumors, the rationale is currently only alleged. The role of BRCA mutation in gastrointestinal cancers is the subject of this review. In particular, we aim to provide the latest updates about novel therapeutic strategies that, exploiting DNA repair defects, promise to shape the future therapeutic scenario of GI cancers.
Not All Wnt Activation Is Equal: Ligand-Dependent versus Ligand-Independent Wnt Activation in Colorectal Cancer
Authors: Kleeman Sam O. , Leedham Simon J.
Published: November 2020

Wnt signaling is ubiquitously activated in colorectal tumors and driver mutations are identified in genes such as APC, CTNNB1, RNF43 and R-spondin (RSPO2/3). Adenomatous polyposis coli (APC) and CTNNB1 mutations lead to downstream constitutive activation (ligand-independent), while RNF43 and RSPO mutations require exogenous Wnt ligand to activate signaling (ligand-dependent). Here, we present evidence that these mutations are not equivalent and that ligand-dependent and ligand-independent tumors differ in terms of underlying Wnt biology, molecular pathogenesis, morphology and prognosis. These non-overlapping characteristics can be harnessed to develop biomarkers and targeted treatments for ligand-dependent tumors, including porcupine inhibitors, anti-RSPO3 antibodies and asparaginase. There is emerging evidence that these therapies may synergize with immunotherapy in ligand-dependent tumors. In summary, we propose that ligand-dependent tumors are an underappreciated separate disease entity in colorectal cancer.
Radiation Induced Upregulation of DNA Sensing Pathways is Cell-Type Dependent and Can Mediate the Off-Target Effects
Authors: Jesenko Tanja , Bosnjak Masa , Markelc Bostjan , Sersa Gregor , Znidar Katarina , Heller Loree , Cemazar Maja
Published: November 2020

Irradiation of tumors generates danger signals and inflammatory cytokines that promote the off-target bystander and abscopal effects, evident especially when radiotherapy is administered in combination with the immune checkpoint inhibitors (ICI). The underlying mechanisms are not fully understood; however, cGAS-STING pathway was recognized as the main mediator. In our study, we demonstrate by immunofluorescent staining that tumor cells as well as macrophages, cell types abundant in the tumor microenvironmeent (TME) accumulate DNA in their cytosol soon after irradiation. This accumulation activated several distinct DNA sensing pathways, most prominently activated DNA sensors being DDX60, DAI, and p204 in tumor cells and DDX60, DAI, p204, and RIG-I in macrophages as determined by PCR and immunofluorescence imaging studies. This was accompanied by increased expression of cytokines evaluated by flow cytometry, TNFα, and IFNβ in tumor cells and IL1β and IFNβ in macrophages, which can alter the TME and mediate off-target effects (bystander or abscopal effects). These results give insight into the mechanisms involved in the stimulation of antitumor immunity by radiation.
The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes
Authors: Hu Dong Gui , Mackenzie Peter I. , Nair Pramod C. , McKinnon Ross A. , Meech Robyn
Published: November 2020

ADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehensive analyses of pan-cancer datasets from the Cancer Genome Atlas (TCGA) revealed differential intratumoral expression profiles for ADME genes in 21 different cancer types. Most genes also showed high interindividual variability within cancer-specific patient cohorts. Using Kaplan-Meier plots and logrank tests, we showed that intratumoral expression levels of twenty of the thirty-two core ADME genes were associated with overall survival (OS) in these cancers. Of these genes, five showed significant association with unfavourable OS in three cancers, including SKCM (ABCC2, GSTP1), KIRC (CYP2D6, CYP2E1), PAAD (UGT2B7); sixteen showed significant associations with favourable OS in twelve cancers, including BLCA (UGT2B15), BRCA (CYP2D6), COAD (NAT1), HNSC (ABCB1), KIRC (ABCG2, CYP3A4, SLC22A2, SLC22A6), KIRP (SLC22A2), LIHC (CYP2C19, CYP2C8, CYP2C9, CYP3A5, SLC22A1), LUAD (SLC15A2), LUSC (UGT1A1), PAAD (ABCB1), SARC (ABCB1), and SKCM (ABCB1, DYPD). Overall, these data provide compelling evidence supporting ADME genes as prognostic biomarkers and potential therapeutic targets. We propose that intratumoral expression of ADME genes may impact cancer patient survival by multiple mechanisms that can include metabolizing/transporting anticancer drugs, activating anticancer drugs, and metabolizing/transporting a variety of endogenous molecules involved in metabolically fuelling cancer cells and/or controlling pro-growth signalling pathways.
Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options
Authors: Personeni Nicola , Lleo Ana , Pressiani Tiziana , Colapietro Francesca , Openshaw Mark Robert , Stavraka Chara , Pouptsis Athanasios , Pinato David James , Rimassa Lorenza
Published: November 2020

Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.
The Origin of Au/Ce1-xZrxO2 Catalyst’s Active Sites in Low-Temperature CO Oxidation
Authors: Dobrosz-Gómez Izabela , Gómez-García Miguel-Ángel , Rynkowski Jacek Michał
Published: November 2020

Gold catalysts have found applications in many reactions of both industrial and environmental importance. Great interest has been paid to the development of new processes that reduce energy consumption and minimize pollution. Among these reactions, the catalytic oxidation of carbon monoxide (CO) is an important one, considering that a high concentration of CO in the atmosphere creates serious health and environmental problems. This paper examines the most important achievements and conclusions arising from the own authorship contributions concerning (2 wt. % Au)/Ce1−xZrxO2 catalyst’s active sites in low-temperature CO oxidation. The main findings of the present review are: (1) The effect of preparing conditions on Au crystallite size, highlighting some of the fundamental underpinnings of gold catalysis: the Au surface composition and the poisoning effect of residual chloride on the catalytic activity of (2 wt. % Au)/Ce1−xZrxO2 catalysts in CO oxidation; (2) The identification of ion clusters related to gold and their effect on catalyst’ surface composition; (3) The importance of physicochemical properties of oxide support (e.g., its particle size, oxygen mobility at low temperature and redox properties) in the creation of catalytic performance of Au catalysts; (4) The importance of oxygen vacancies, on the support surface, as the centers for oxygen molecule activation in CO reaction; (5) The role of moisture (200–1000 ppm) in the generation of enhanced CO conversion; (6) The Au-assisted Mars-van Krevelen (MvK) adsorption–reaction model was pertinent to describe CO oxidation mechanism. The principal role of Au in CO oxidation over (2 wt. % Au)/Ce1−xZrxO2 catalysts was related to the promotion in the transformation process of reversibly adsorbed or inactive surface oxygen into irreversibly adsorbed active species; (7) Combination of metallic gold (Au0) and Au-OH species was proposed as active sites for CO adsorption. These findings can help in the optimization of Au-containing catalysts.
The Effect of Shape-Controlled Pt and Pd Nanoparticles on Selective Catalytic Hydrodechlorination of Trichloroethylene
Authors: Sarıbıyık Oğuz Yunus , Weilach Christian , Serin Selahattin , Rupprechter Günther
Published: November 2020

Tailoring the shape of nanoscale materials enables obtaining morphology-controlled surfaces exhibiting specific interactions with reactants during catalytic reactions. The specifics of nanoparticle surfaces control the catalytic performance, i.e., activity and selectivity. In this study, shape-controlled Platinum (Pt) and Palladium (Pd) nanoparticles with distinct morphology were produced, i.e., cubes and cuboctahedra for Pt and spheres and polyhedra/multiple-twins for Pd, with (100), (111 + 100), curved/stepped and (111) facets, respectively. These particles with well-tuned surfaces were subsequently deposited on a Zirconium oxide (ZrO2) support. The morphological characteristics of the particles were determined by high resolution transmission electron microscopy (HR-TEM) and X-ray diffraction (XRD), while their adsorption properties were investigated by Fourier transform infrared spectroscopy (FTIR) of CO adsorbed at room temperature. The effect of the nanoparticle shape and surface structure on the catalytic performance in hydrodechlorination (HDCl) of trichloroethylene (TCE) was examined. The results show that nanoparticles with different surface orientations can be employed to affect selectivity, with polyhedral and multiply-twinned Pd exhibiting the best ethylene selectivity.
Development of a New Arylamination Reaction Catalyzed by Polymer Bound 1,3-(Bisbenzimidazolyl) Benzene Co(II) Complex and Generation of Bioactive Adamanate Amines
Authors: Chumadathil Pookunoth Baburajeev , Eshwar Rao Shilpa , Deveshegowda Suresha , Kashinath Metri Prashant , Fazl-Ur-Rahman Kashifa , Periyasamy Ganga , Virupaiah Gayathri , Priya Babu , Pandey Vijay , E. Lobie Peter , Knchugarakoppal Subbegowda Rangappa , Basappa
Published: November 2020

We herein report the preparation and characterization of an inexpensive polymer supported 1,3-bis(benzimidazolyl)benzeneCo(II) complex [PS-Co(BBZN)Cl2] as a catalyst by using the polymer (divinylbenzene cross-linked chloromethylated polystyrene), on which 1,3-bis(benzimidazolyl)benzeneCo(II) complex (PS-Co(BBZN)Cl2) has been immobilized. This catalyst was employed to develop arylamination reaction and robustness of the same reaction was demonstrated by synthesizing various bioactive adamantanyl-tethered-biphenylamines. Our synthetic methodology was much improved than reported methods due to the use of an inexpensive and recyclable catalyst.