bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods Favoring Homology-Directed Repair Choice in Response to CRISPR/Cas9 Induced-Double Strand Breaks
Authors: Yang Han , Ren Shuling , Yu Siyuan , Pan Haifeng , Li Tingdong , Ge Shengxiang , Zhang Jun , Xia Ningshao
Published: September 2020

Precise gene editing is—or will soon be—in clinical use for several diseases, and more applications are under development. The programmable nuclease Cas9, directed by a single-guide RNA (sgRNA), can introduce double-strand breaks (DSBs) in target sites of genomic DNA, which constitutes the initial step of gene editing using this novel technology. In mammals, two pathways dominate the repair of the DSBs—nonhomologous end joining (NHEJ) and homology-directed repair (HDR)—and the outcome of gene editing mainly depends on the choice between these two repair pathways. Although HDR is attractive for its high fidelity, the choice of repair pathway is biased in a biological context. Mammalian cells preferentially employ NHEJ over HDR through several mechanisms: NHEJ is active throughout the cell cycle, whereas HDR is restricted to S/G2 phases; NHEJ is faster than HDR; and NHEJ suppresses the HDR process. This suggests that definitive control of outcome of the programmed DNA lesioning could be achieved through manipulating the choice of cellular repair pathway. In this review, we summarize the DSB repair pathways, the mechanisms involved in choice selection based on DNA resection, and make progress in the research investigating strategies that favor Cas9-mediated HDR based on the manipulation of repair pathway choice to increase the frequency of HDR in mammalian cells. The remaining problems in improving HDR efficiency are also discussed. This review should facilitate the development of CRISPR/Cas9 technology to achieve more precise gene editing.
Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies
Authors: Monda Emanuele , Palmiero Giuseppe , Rubino Marta , Verrillo Federica , Amodio Federica , Di Fraia Francesco , Pacileo Roberta , Fimiani Fabio , Esposito Augusto , Cirillo Annapaola , Fusco Adelaide , Moscarella Elisabetta , Frisso Giulia , Russo Maria Giovanna , Pacileo Giuseppe , Calabrò Paolo , Scudiero Olga , Caiazza Martina , Limongelli Giuseppe
Published: September 2020

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.
Morpholino Analogues of Fingolimod as Novel and Selective S1P1 Ligands with In Vivo Efficacy in a Mouse Model of Experimental Antigen-Induced Encephalomyelitis
Authors: Stepanovska Bisera , Zivkovic Aleksandra , Enzmann Gaby , Tietz Silvia , Homann Thomas , Kleuser Burkhard , Engelhardt Britta , Stark Holger , Huwiler Andrea
Published: September 2020

Multiple sclerosis (MS) is a chronic, inflammatory, autoimmune disease of the central nervous system (CNS) which is associated with lower life expectancy and disability. The experimental antigen-induced encephalomyelitis (EAE) in mice is a useful animal model of MS, which allows exploring the etiopathogenetic mechanisms and testing novel potential therapeutic drugs. A new therapeutic paradigm for the treatment of MS was introduced in 2010 through the sphingosine 1-phosphate (S1P) analogue fingolimod (FTY720, Gilenya®), which acts as a functional S1P1 antagonist on T lymphocytes to deplete these cells from the blood. In this study, we synthesized two novel structures, ST-1893 and ST-1894, which are derived from fingolimod and chemically feature a morpholine ring in the polar head group. These compounds showed a selective S1P1 activation profile and a sustained S1P1 internalization in cultures of S1P1-overexpressing Chinese hamster ovary (CHO)-K1 cells, consistent with a functional antagonism. In vivo, both compounds induced a profound lymphopenia in mice. Finally, these substances showed efficacy in the EAE model, where they reduced clinical symptoms of the disease, and, on the molecular level, they reduced the T-cell infiltration and several inflammatory mediators in the brain and spinal cord. In summary, these data suggest that S1P1-selective compounds may have an advantage over fingolimod and siponimod, not only in MS but also in other autoimmune diseases.
HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution—A Promising New Tool in Solid Organ Preservation
Authors: Mohr Annika , Brockmann Jens G. , Becker Felix
Published: September 2020

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.
Biological Responses to Cadmium Stress in Liverwort Conocephalum conicum (Marchantiales)
Authors: Maresca Viviana , Lettieri Gennaro , Sorbo Sergio , Piscopo Marina , Basile Adriana
Published: September 2020

Oxidative damage (production and localization of reactive oxygen species) and related response mechanisms (activity of antioxidant enzymes), and induction of Heat Shock Protein 70 expression, have been studied in the toxi-tolerant liverwort Conocephalum conicum (Marchantiales) in response to cadmium stress using two concentrations (36 and 360 µM CdCl2). Cadmium dose-dependent production of reactive oxygen species (ROS) and related activity of antioxidant enzymes was observed. The expression level of heat shock protein (Hsp)70, instead, was higher at 36 µM CdCl2 in comparison with the value obtained after exposure to 360 µM CdCl2, suggesting a possible inhibition of the expression of this stress gene at higher cadmium exposure doses. Biological responses were related to cadmium bioaccumulation. Since C. conicum was able to respond to cadmium stress by modifying biological parameters, we discuss the data considering the possibility of using these biological changes as biomarkers of cadmium pollution.
Investigations on Physico-Mechanical and Spectral Studies of Zn2+ Doped P2O5-Based Bioglass System
Authors: Mohan Babu M. , Syam Prasad P. , Hima Bindu S. , Prasad A. , Venkateswara Rao P. , Putenpurayil Govindan Nibu , Veeraiah N. , Özcan Mutlu
Published: September 2020

ZnO incorporated phosphate based bioglasses with the composition xZnO–22Na2O–24CaO–(54-X)P2O5 (where X = 2, 4, 6, 8, 10 mol%) were developed by melt-quenching process. The physical, thermal and other structural properties of the glasses were studied in detail. By employing various characterization techniques such as X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) in addition to the energy dispersion spectroscopy (EDS), and Raman spectroscopy, the structural properties were analyzed. Interestingly, physical, thermal and mechanical properties were enhanced with the increasing content of zinc oxide up to 8 mol%, due to the presence of more ionic nature of P–O–Zn bonds than P–O–P bonds in the glass network. The FTIR and Raman analysis revealed the evolution of the phosphate network with increasing zinc concentration and leads to progressive depolymerisation of the glass network. The obtained results from the physical and structural properties of these zinc added calcium phosphate glasses support their potential to use as bone implant applications.
Developing an Explanatory Risk Management Model to Comprehend the Employees’ Intention to Leave Public Sector Organization
Authors: Prihandinisari Carolina , Rahman Azizur , Hicks John
Published: September 2020

This paper reviews research and theory on the important topic of labour turnover resulting from issues related to job performance and/or job satisfaction which have, in turn, been initiated by changes in work motivation. We focus on labour turnover in the public sector—a neglected area of public administration research—and propose an explanatory model of the development of the intention to leave an organization. The model first describes the relationships between work motivation and job performance and/or job satisfaction. It then explains how changes in performance and/or satisfaction result in the formation of an intention to leave public service employment. The paper concludes by identifying key areas for future research.
Spinel of Nickel-Cobalt Oxide with Rod-Like Architecture as Electrocatalyst for Oxygen Evolution Reaction
Authors: Dymerska Anna , Kukułka Wojciech , Biegun Marcin , Mijowska Ewa
Published: September 2020

The renewable energy technologies require electrocatalysts for reactions, such as the oxygen and/or hydrogen evolution reaction (OER/HER). They are complex electrochemical reactions that take place through the direct transfer of electrons. However, mostly they have high over-potentials and slow kinetics, that is why they require electrocatalysts to lower the over-potential of the reactions and enhance the reaction rate. The commercially used catalysts (e.g., ruthenium nanoparticles—Ru, iridium nanoparticles—Ir, and their oxides: RuO2, IrO2, platinum—Pt) contain metals that have poor stability, and are not economically worthwhile for widespread application. Here, we propose the spinel structure of nickel-cobalt oxide (NiCo2O4) fabricated to serve as electrocatalyst for OER. These structures were obtained by a facile two-step method: (1) One-pot solvothermal reaction and subsequently (2) pyrolysis or carbonization, respectively. This material exhibits novel rod-like morphology formed by tiny spheres. The presence of transition metal particles such as Co and Ni due to their conductivity and electron configurations provides a great number of active sites, which brings superior electrochemical performance in oxygen evolution and good stability in long-term tests. Therefore, it is believed that we propose interesting low-cost material that can act as a super stable catalyst in OER.
Biocompatibility and Bioactivity of Set Direct Pulp Capping Materials on Human Dental Pulp Stem Cells
Authors: Kim Yemi , Lee Donghee , Song Dani , Kim Hye-Min , Kim Sin-Young
Published: September 2020

In this study, we assessed the biocompatibility and bioactivity of various pulp capping materials—ProRoot MTA (Dentsply Tulsa Dental Specialties), Biodentine (Septodont), TheraCal LC (Bisco), and Dycal (Dentsply Caulk)—on human dental pulp stem cells (hDPSCs). Experimental disks (diameter, 7 mm; height, 4 mm) were stored in a humified incubator at 37 °C for 48 h. Then, the pulp capping materials were tested for cytotoxic effects by methyl-thiazoldiphenyl-tetrazolium and scratch wound healing assays, and for mineralization potential by Alizarin red S (ARS) staining assay and alkaline phosphatase enzyme (ALP) activity. Cell viability and cell migration did not significantly differ between ProRoot MTA, Biodentine, and control (p > 0.05). TheraCal LC exhibited slower cell migration on days 2–4 compared to control (p < 0.05), and Dycal showed no cell migration. ALP activity was highest with Biodentine on days 10 and 14, and was lowered with TheraCal LC and Dycal (p < 0.05). In the ARS assay, hDPSCs grown in ProRoot MTA and TheraCal LC eluates showed significantly increased mineralized nodule formation on day 21 compared to Biodentine, Dycal, and control (p < 0.05). These findings indicate that ProRoot MTA, Biodentine, and TheraCal LC exhibit better biocompatibility and bioactivity than Dycal.
Stress and Microstructure Evolution in Mo Thin Films without or with Cover Layers during Thermal-Cycling
Authors: Park Eunmi , Seifert Marietta , Rane Gayatri K. , Menzel Siegfried B. , Gemming Thomas , Nielsch Kornelius
Published: September 2020

The intrinsic stress behavior and microstructure evolution of Molybdenum thin films were investigated to evaluate their applicability as a metallization in high temperature microelectronic devices. For this purpose, 100 nm thick Mo films were sputter-deposited without or with an AlN or SiO2 cover layer on thermally oxidized Si substrates. The samples were subjected to thermal cycling up to 900 °C in ultrahigh vacuum; meanwhile, the in-situ stress behavior was monitored by a laser based Multi-beam Optical Sensor (MOS) system. After preannealing at 900 °C for 24 h, the uncovered films showed a high residual stress at room temperature and a plastic behavior at high temperatures, while the covered Mo films showed an almost entirely elastic deformation during the thermal cycling between room temperature and 900 °C with hardly any plastic deformation, and a constant stress value during isothermal annealing without a notable creep. Furthermore, after thermal cycling, the Mo films without as well as with a cover layer showed low electrical resistivity (≤10 μΩ·cm).
Products of Finite Connected Subgroups
Authors: Gállego María Pilar , Hauck Peter , Kazarin Lev S. , Martínez-Pastor Ana , Pérez-Ramos María Dolores
Published: September 2020

For a non-empty class of groups L, a finite group G=AB is said to be an L-connected product of the subgroups A and B if ⟨a,b⟩∈L for all a∈A and b∈B. In a previous paper, we prove that, for such a product, when L=S is the class of finite soluble groups, then [A,B] is soluble. This generalizes the theorem of Thompson that states the solubility of finite groups whose two-generated subgroups are soluble. In the present paper, our result is applied to extend to finite groups previous research about finite groups in the soluble universe. In particular, we characterize connected products for relevant classes of groups, among others, the class of metanilpotent groups and the class of groups with nilpotent derived subgroup. Additionally, we give local descriptions of relevant subgroups of finite groups.
New Fusion Algorithm-Reinforced Pilot Control for an Agricultural Tricopter UAV
Authors: Tran Huu Khoa , Chiou Juing-Shian , Dang Viet-Hung
Published: September 2020

Currently, fuzzy proportional integral derivative (PID) controller schemes, which include simplified fuzzy reasoning decision methodologies and PID parameters, are broadly and efficaciously practiced in various fields from industrial applications, military service, to rescue operations, civilian information and also horticultural observation and agricultural surveillance. A fusion particle swarm optimization (PSO)–evolutionary programming (EP) algorithm, which is an improved version of the stochastic optimization strategy PSO, was presented for designing and optimizing controller gains in this study. The mathematical calculations of this study include the reproduction of EP with PSO. By minimizing the integral of the absolute error (IAE) criterion that is used for estimating the system response as a fitness function, the obtained integrated design of the fusion PSO–EP algorithm generated and updated the new elite parameters for proposed controller schemes. This progression was used for the complicated non-linear systems of the attitude-control pilot models of a tricopter unmanned aerial vehicle (UAV) to demonstrate an improvement on the performance in terms of rapid response, precision, reliability, and stability.
Priority Multi-Server Queueing System with Heterogeneous Customers
Authors: Klimenok Valentina , Dudin Alexander , Vishnevsky Vladimir
Published: September 2020

In this paper, we analyze a multi-server queueing system with heterogeneous customers that arrive according to a marked Markovian arrival process. Customers of two types differ in priorities and parameters of phase type distribution of their service time. The queue under consideration can be used to model the processes of information transmission in telecommunication networks in which often the flow of information is the superposition of several types of flows with correlation of inter-arrival times within each flow and cross-correlation. We define the process of information transmission as the multi-dimensional Markov chain, derive the generator of this chain and compute its stationary distribution. Expressions for computation of various performance measures of the system, including the probabilities of loss of customers of different types, are presented. Output flow from the system is characterized. The presented numerical results confirm the high importance of account of correlation in the arrival process. The values of important performance measures for the systems with the correlated arrival process are essentially different from the corresponding values for the systems with the stationary Poisson arrival process. Measurements in many real world systems show poor approximation of real flows by such an arrival process. However, this process is still popular among the telecommunication engineers due to the evident existing gap between the needs of adequately modeling the real life systems and the current state of the theory of algorithmic methods of queueing theory.
An Efficient and Accurate Method for the Conservative Swift–Hohenberg Equation and Its Numerical Implementation
Authors: Lee Hyun Geun
Published: September 2020

The conservative Swift–Hohenberg equation was introduced to reformulate the phase-field crystal model. A challenge in solving the conservative Swift–Hohenberg equation numerically is how to treat the nonlinear term to preserve mass conservation without compromising efficiency and accuracy. To resolve this problem, we present a linear, high-order, and mass conservative method by placing the linear and nonlinear terms in the implicit and explicit parts, respectively, and employing the implicit-explicit Runge–Kutta method. We show analytically that the method inherits the mass conservation. Numerical experiments are presented demonstrating the efficiency and accuracy of the proposed method. In particular, long time simulation for pattern formation in 2D is carried out, where the phase diagram can be observed clearly. The MATLAB code for numerical implementation of the proposed method is provided in Appendix.
Strong Tolerance and Strong Universality of Interval Eigenvectors in a Max-Łukasiewicz Algebra
Authors: Gavalec Martin , Němcová Zuzana , Plavka Ján
Published: September 2020

The Łukasiewicz conjunction (sometimes also considered to be a logic of absolute comparison), which is used in multivalued logic and in fuzzy set theory, is one of the most important t-norms. In combination with the binary operation ‘maximum’, the Łukasiewicz t-norm forms the basis for the so-called max-Łuk algebra, with applications to the investigation of systems working in discrete steps (discrete events systems; DES, in short). Similar algebras describing the work of DES’s are based on other pairs of operations, such as max-min algebra, max-plus algebra, or max-T algebra (with a given t-norm, T). The investigation of the steady states in a DES leads to the study of the eigenvectors of the transition matrix in the corresponding max-algebra. In real systems, the input values are usually taken to be in some interval. Various types of interval eigenvectors of interval matrices in max-min and max-plus algebras have been described. This paper is oriented to the investigation of strong, strongly tolerable, and strongly universal interval eigenvectors in a max-Łuk algebra. The main method used in this paper is based on max-Ł linear combinations of matrices and vectors. Necessary and sufficient conditions for the recognition of strong, strongly tolerable, and strongly universal eigenvectors have been found. The theoretical results are illustrated by numerical examples.
Transfer Learning for Stenosis Detection in X-ray Coronary Angiography
Authors: Ovalle-Magallanes Emmanuel , Avina-Cervantes Juan Gabriel , Cruz-Aceves Ivan , Ruiz-Pinales Jose
Published: September 2020

Coronary artery disease is the most frequent type of heart disease caused by an abnormal narrowing of coronary arteries, also called stenosis or atherosclerosis. It is also the leading cause of death globally. Currently, X-ray Coronary Angiography (XCA) remains the gold-standard imaging technique for medical diagnosis of stenosis and other related conditions. This paper presents a new method for the automatic detection of coronary artery stenosis in XCA images, employing a pre-trained (VGG16, ResNet50, and Inception-v3) Convolutional Neural Network (CNN) via Transfer Learning. The method is based on a network-cut and fine-tuning approach. The optimal cut and fine-tuned layers were selected following 20 different configurations for each network. The three networks were fine-tuned using three strategies: only real data, only artificial data, and artificial with real data. The synthetic dataset consists of 10,000 images (80% for training, 20% for validation) produced by a generative model. These different configurations were analyzed and compared using a real dataset of 250 real XCA images (125 for testing and 125 for fine-tuning), regarding their randomly initiated CNNs and a fourth custom CNN, trained as well with artificial and real data. The results showed that pre-trained VGG16, ResNet50, and Inception-v3 cut on an early layer and fine-tuned, overcame the referencing CNNs performance. Specifically, Inception-v3 provided the best stenosis detection with an accuracy of 0.95, a precision of 0.93, sensitivity, specificity, and F1 score of 0.98, 0.92, and 0.95, respectively. Moreover, a class activation map is applied to identify the high attention regions for stenosis detection.
Fuzzy Set Models for Economic Resilience Estimation
Authors: Nedosekin Alexey , Abdoulaeva Zinaida , Konnikov Evgenii , Zhuk Alexander
Published: September 2020

(1) Presented models are proposed for analyzing the resilience of an economic system in a framework of a 4 × 6 matrix, the core of which is a balanced scorecard (BSC). Matrix rows present strategic perspectives, matrix columns present strategic maps. (2) Resilience assessment models are based on fuzzy logic and soft computing, combined with systemic-cybernetic approaches to building presented models. The simplest models are Zadeh linguistic variables that describe key performance indicators (KPIs). The BSC model is an acyclic graph with fuzzy links that are calibrated based on special rules. The information obtained during the simulation is aggregated through a matrix aggregate calculator (MAC). (3) The BSC model was used to assess the economic resilience of a small electrical enterprise in Russia, numbering 2000 people with revenue of approximately 100 million euros per year. The BSC model included about 70 KPIs and 200 fuzzy links. Also, the presented MAC model was applied to obtain linguistic classifiers in five basic industries, using the example of a comparative analysis of 82 international industrial companies. (4) The proposed models allow not only to describe the economic system and its external environment, but also solutions aimed at increasing resilience, within the unified framework.
Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds
Authors: Molnár Barnabás , Gopisetty Mohana Krishna , Adamecz Dóra Izabella , Kiricsi Mónika , Frank Éva
Published: September 2020

Although the hormone independent cytotoxic activity of several estradiol derivatives endowed with a simple substituent at C-2 has been reported so far, 2-heterocyclic and 2,3-condensed analogs are less investigated from both synthetic and pharmacological points of view. Therefore, novel A-ring-connected 2-pyrazoles of estradiol and, for comparison, their structurally simplified non-steroidal pairs were synthesized from estradiol 3-methyl ether and 6-methoxy-1,2,3,4-tetrahydronaphthalene. Friedel-Crafts acetylation of the protected phenolic compounds and subsequent O-demethylation led to ortho-substituted derivatives regioselectively, which were converted to arylhydrazones with phenylhydrazine, 4-tolylhydrazine and 4-chloro-phenylhydrazine, respectively, under microwave conditions. The hydrazones were subjected to cyclization with the Vilsmeier-Haack reagent immediately after preparation and the ring closure/formylation sequence resulted in steroidal and non-steroidal 4′-formylpyrazoles in moderate to good yields. During reductive transformations, 4-hydroxymethyl-pyrazoles were obtained, while oxidative lactonization of the 4-formylpyrazole moiety with the phenolic OH in the presence of the Jones reagent afforded A-ring-integrated pyrazolocoumarin hybrids and related analogs. Steroidal pyrazoles, which were produced as C-17 acetates due to acetylation of C-17 OH during the primary Friedel-Crafts reaction, underwent deacetylation in alkaline methanol to furnish 2-heterocyclic estradiol derivatives. Pharmacological studies revealed the overall and cancer cell-specific cytotoxicity of the derivatives and the half maximal inhibitory concentrations were obtained for the most promising compounds.
Structure and Function of the Human Ryanodine Receptors and Their Association with Myopathies—Present State, Challenges, and Perspectives
Authors: Bauerová-Hlinková Vladena , Hajdúchová Dominika , Bauer Jacob A.
Published: September 2020

Cardiac arrhythmias are serious, life-threatening diseases associated with the dysregulation of Ca2+ influx into the cytoplasm of cardiomyocytes. This dysregulation often arises from dysfunction of ryanodine receptor 2 (RyR2), the principal Ca2+ release channel. Dysfunction of RyR1, the skeletal muscle isoform, also results in less severe, but also potentially life-threatening syndromes. The RYR2 and RYR1 genes have been found to harbor three main mutation “hot spots”, where mutations change the channel structure, its interdomain interface properties, its interactions with its binding partners, or its dynamics. In all cases, the result is a defective release of Ca2+ ions from the sarcoplasmic reticulum into the myocyte cytoplasm. Here, we provide an overview of the most frequent diseases resulting from mutations to RyR1 and RyR2, briefly review some of the recent experimental structural work on these two molecules, detail some of the computational work describing their dynamics, and summarize the known changes to the structure and function of these receptors with particular emphasis on their N-terminal, central, and channel domains.
Understanding the Medical Chemistry of the Cannabis Plant is Critical to Guiding Real World Clinical Evidence
Authors: Ladha Karim S. , Ajrawat Prabjit , Yang Yi , Clarke Hance
Published: September 2020

While cannabis has been consumed for thousands of years, the medical-legal landscape surrounding its use has dramatically evolved over the past decades. Patients are turning to cannabis as a therapeutic option for several medical conditions. Given the surge in interest over the past decades there exists a major gap in the literature with respect to understanding the products that are currently being consumed by patients. The current perspective highlights the lack of relevance within the current literature towards understanding the medical chemistry of the products being consumed. The cannabis industry must rigorously invest into understanding what people are consuming from a chemical composition standpoint. This will inform what compounds in addition to Δ9-tetrahydrocannabinol and cannabidiol may be producing physiologic/therapeutic effects from plant based extracts. Only through real-world evidence and a formalized, granular data collection process within which we know the chemical inputs for patients already using or beginning to use medical cannabis, we can come closer to the ability to provide targeted clinical decision making and design future appropriate randomized controlled trials.
Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host–Guest Interactions in the Gas Phase and Condensed Phase
Authors: Lee Jae-ung , Lee Sung-Sik , Lee Sungyul , Oh Han Bin
Published: September 2020

Cyclodextrins (CDs) have drawn a lot of attention from the scientific communities as a model system for host–guest chemistry and also due to its variety of applications in the pharmaceutical, cosmetic, food, textile, separation science, and essential oil industries. The formation of the inclusion complexes enables these applications in the condensed phases, which have been confirmed by nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and other methodologies. The advent of soft ionization techniques that can transfer the solution-phase noncovalent complexes to the gas phase has allowed for extensive examination of these complexes and provides valuable insight into the principles governing the formation of gaseous noncovalent complexes. As for the CDs’ host–guest chemistry in the gas phase, there has been a controversial issue as to whether noncovalent complexes are inclusion conformers reflecting the solution-phase structure of the complex or not. In this review, the basic principles governing CD’s host–guest complex formation will be described. Applications and structures of CDs in the condensed phases will also be presented. More importantly, the experimental and theoretical evidence supporting the two opposing views for the CD–guest structures in the gas phase will be intensively reviewed. These include data obtained via mass spectrometry, ion mobility measurements, infrared multiphoton dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations.
Anti-Inflammatory Effects of a Cordyceps sinensis Mycelium Culture Extract (Cs-4) on Rodent Models of Allergic Rhinitis and Asthma
Authors: Chen Jihang , Chan Wing Man , Leung Hoi Yan , Leong Pou Kuan , Yan Choly Tat Ming , Ko Kam Ming
Published: September 2020

Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma.
Effect of Polyethylene Glycol Incorporation in Electron Transport Layer on Photovoltaic Properties of Perovskite Solar Cells
Authors: Liu Bo-Tau , Guo Bo-Wei , Balamurugan Rathinam
Published: September 2020

Due to the characteristics of high electron mobility, ambient stability, proper energy level, and low processing temperature, zinc oxide (ZnO) has become a very promising electron transport material for photovoltaics. However, perovskite solar cells fabricated with ZnO reveal low efficiency because perovskite crystals may decompose thermally on the surface of ZnO as a result of proton transfer reactions. In this study, we are the first to incorporate an inexpensive, non-toxic polyethylene glycol (PEG) into ZnO and explore the passivation effect on the electron transport layer of perovskite solar cells. Suspension stability, surface roughness, electrical conductivity, crystal size, and photovoltaic properties with respect to the PEG incorporation are analyzed. The experimental results revealed that PEG incorporation effectively passivated the surface defects of ZnO, increased the electrical conductivity, and suppressed the charge recombination. The photocurrent density could increase from 15.2 to 19.2 mA/cm2, an increase of 27%.
Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet
Authors: Wang Yi-Chun , Juan Shu-Hui , Chou Chu-Lin , Hsieh Tsung-Cheng , Wu Jung-Lun , Fang Te-Chao
Published: September 2020

The effects of ketoanalogues (KA) supplementation on mortality and progression to dialysis in patients with pre-dialysis stage 5 chronic kidney disease (CKD) receiving a low-protein diet (LPD) remain ambiguous. From Taiwan’s National Health Insurance Research Database during 1996–2011, 165 patients with pre-dialysis CKD on an LPD (0.6 g/kg/day) with KA supplementation were matched with 165 patients with pre-dialysis CKD on an LPD without KA supplementation. Of the 165 patients with advanced CKD receiving KA supplementation, 34 (20.6%) died, and 124 (75.2%) underwent long-term dialysis during the study period. There was no significant difference in mortality between the KA-user group and the KA-nonuser group (adjusted hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.68–2.93; p = 0.355). KA supplementation significantly increased long-term dialysis risk (adjusted HR, 1.41; 95% CI, 1.04–1.90; p = 0.025) and combined outcome risk (defined as long-term dialysis and death; adjusted HR, 1.37; 95% CI, 1.02–1.83; p = 0.034). KA supplementation also increased long-term dialysis risk (adjusted HR, 1.49; 95% CI, 1.00–2.20; p = 0.048) in the subgroup of pre-dialysis patients with diabetes mellitus (DM), but not in those patients without DM. In conclusion, KA supplementation might increase long-term dialysis risk in patients with advanced CKD receiving an LPD, but it did not increase mortality.
Low Content of Cyclosporine A and Its Metabolites in the Colostrum of Post-Transplant Mothers
Authors: Kociszewska-Najman Bożena , Mazanowska Natalia , Borek-Dzięcioł Beata , Pączek Leszek , Samborowska Emilia , Szpotańska-Sikorska Monika , Pietrzak Bronisława , Dadlez Michał , Wielgoś Mirosław
Published: September 2020

The rate of post-transplant mothers who breastfeed while on immunosuppression is progressively increasing. Data on breastfeeding while on cyclosporine-based regimens are limited. Therefore, we assessed the amount of cyclosporine and its metabolites that might be ingested by a breastfed infant by measuring the concentration of cyclosporine and its metabolites in the colostrum of seven post-transplant mothers. The mean concentration of cyclosporine in the colostrum was 22.40 ± 9.43 mcg/L, and the estimated mean daily dose of the drug was 1049.22 ± 397.41 ng/kg/24 h. Only three metabolites (AM1, DHCsA, and THCsA) had mean colostrum amounts comparable to or higher than cyclosporine itself, with the daily doses being 468.51 ± 80.37, 2757.79 ± 1926.11, and 1044.76 ± 948.56 ng/kg/24 h, respectively. Our results indicate a low transfer of cyclosporine and its metabolites into the colostrum in the first two days postpartum and confirm the emerging change to the policy on breastfeeding among post-transplant mothers. A full assessment of the safety of immunosuppressant exposure via breastmilk will require further studies with long-term follow-ups of breastfed children.
The Effect of Citric Acid, NaCl, and CaCl2 on Qualitative Changes of Horse Meat in Cold Storage
Authors: Stanisławczyk Renata , Rudy Mariusz , Gil Marian , Duma-Kocan Paulina , Dziki Dariusz , Rudy Stanisław
Published: September 2020

In this study, we aimed to analyze the effect of citric acid, NaCl, and CaCl2 on the qualitative changes of horse meat during cold storage. The study material was the longest dorsal muscles (M. longissimus dorsi (LM)) obtained from twelve half-carcasses of horses. The muscle was cut into five steaks, each of which was about 3 cm thick. One sample was kept as a control sample, and the remaining ones were treated with NaCl, citric acid, and CaCl2 (0.2 M and 0.3 M). The study material was obtained 24 h after the slaughter of the animals and was marinated in solution (citric acid and 0.2 M and 0.3 M calcium chloride) and by sprinkling and rubbing (sodium chloride). The applied treatments significantly (p ≤ 0.05) improved the texture parameters of horse meat (univariate analysis of variance). Citric acid caused deterioration of the study material with respect to the binding and retention of intrinsic water. Among the tested material, the lightest color of the meat was obtained for sample marinated in 0.3 M CaCl2. However, the darkest color of the meat was obtained after the addition of NaCl.
Preliminary Results of Ship Detection Technique by Wake Pattern Recognition in SAR Images
Authors: Graziano Maria Daniela
Published: September 2020

Recently, international agencies for border security ask for an improvement of the actual Maritime Situational Awareness. This manuscript presents preliminary results of a detection technique of go-fast boats, whose utilization in illegal affairs is strongly increasing. Their detection is very challenging since: (i) their echo is not visible in SAR images, and (ii) the illegal activities are carried out in the nighttime making useless the optical sensors. However, their wakes are very persistent and extent in SAR images for some kilometers. Hence, the manuscript shows an innovative deterministic methodology for the ship detection based on the wake signature. It firstly identifies pixels crossed by the wakes, whose presence is, then, validated in two steps. The first level of validation estimated how prominent the wake components are with respect to their background. The second level of validation exploits the presence of the wakes among neighbor pixels. The approach has been applied on ships imaged by TerraSAR-X mission showing the same peculiarities of go-fast boats. Results highlight the potentialities of the proposed approach, which can be also conceived as a subsequent step in a hybrid system, whose preliminary wake detection screening is carried out by different techniques.
Machine-Learning Analysis of Voice Samples Recorded through Smartphones: The Combined Effect of Ageing and Gender
Authors: Asci Francesco , Costantini Giovanni , Di Leo Pietro , Zampogna Alessandro , Ruoppolo Giovanni , Berardelli Alfredo , Saggio Giovanni , Suppa Antonio
Published: September 2020

Background: Experimental studies using qualitative or quantitative analysis have demonstrated that the human voice progressively worsens with ageing. These studies, however, have mostly focused on specific voice features without examining their dynamic interaction. To examine the complexity of age-related changes in voice, more advanced techniques based on machine learning have been recently applied to voice recordings but only in a laboratory setting. We here recorded voice samples in a large sample of healthy subjects. To improve the ecological value of our analysis, we collected voice samples directly at home using smartphones. Methods: 138 younger adults (65 males and 73 females, age range: 15–30) and 123 older adults (47 males and 76 females, age range: 40–85) produced a sustained emission of a vowel and a sentence. The recorded voice samples underwent a machine learning analysis through a support vector machine algorithm. Results: The machine learning analysis of voice samples from both speech tasks discriminated between younger and older adults, and between males and females, with high statistical accuracy. Conclusions: By recording voice samples through smartphones in an ecological setting, we demonstrated the combined effect of age and gender on voice. Our machine learning analysis demonstrates the effect of ageing on voice.
A Novel Method about the Representation and Discrimination of Traffic State
Authors: Jiang Junfeng , Chen Qiushi , Xue Jie , Wang Haobo , Chen Zhijun
Published: September 2020

The representation and discrimination of various traffic states play an essential role in solving traffic accidents and congestion as the foundation of traffic state prediction. However, the existing representation of the traffic state usually only considers the road congestion layer and divides the traffic state into congested and unblocked. Representation only at the congestion layer is difficult to reflect the road traffic state comprehensively. Therefore, we select three indicators from the layers of road congestion, road safety, and road stability, respectively, then utilizing K-means to cluster the traffic state. The clustering results can be regarded as a new type for the representation of a traffic state. As a result, the traffic states are divided into four classes, which comprehensively reflects the level of road congestion, safety, and stability. Using the four traffic states obtained from the clustering results as class labels, we applied a multi-layer perceptron (MLP) to classify the different traffic states, and the receiver operating characteristic (ROC) curve is assessed to verify the superiority of the classification results. Finally, a visual display of the real-time traffic state in a city’s central area was given.
Time-Frequency Distribution Map-Based Convolutional Neural Network (CNN) Model for Underwater Pipeline Leakage Detection Using Acoustic Signals
Authors: Xie Yingchun , Xiao Yucheng , Liu Xuyan , Liu Guijie , Jiang Weixiong , Qin Jin
Published: September 2020

Detection technology of underwater pipeline leakage plays an important role in the subsea production system. In this paper, a new method based on the acoustic leak signal collected by a hydrophone is proposed to detect pipeline leakage in the subsea production system. Through the pipeline leakage test, it is found that the radiation noise is a continuous spectrum of the medium and high-frequency noise. Both the increase in pipe pressure and the diameter of the leak hole will narrow the spectral structure and shift the spectrum center towards the low frequencies. Under the same condition, the pipe pressure has a greater impact on the noise; every 0.05 MPa increase in the pressure, the radiation sound pressure level increases by 6-7 dB. The time-frequency images were obtained by processing the acoustic signals using the Ensemble Empirical Mode Decomposition (EEMD) and Hilbert–Huang transform (HHT), and fed into a two-layer Convolutional Neural Network (CNN) for leakage detection. The results show that CNN can correctly identify the degree of pipeline leakage. Hence, the proposed method provides a new approach for the detection of pipeline leakage in underwater engineering applications.
Highly Sensitive Fluorescence Sensor for Carrageenan from a Composite Methylcellulose/Polyacrylate Membrane
Authors: Hassan Riyadh Abdulmalek , Heng Lee Yook , Tan Ling Ling
Published: September 2020

Carrageenans are linear sulphated polysaccharides that are commonly added into confectionery products but may exert a detrimental effect to human health. A new and simpler way of carrageenan determination based on an optical sensor utilizing a methylcellulose/poly(n-butyl acrylate) (Mc/PnBA) composite membrane with immobilized methylene blue (MB) was developed. The hydrophilic Mc polymer membrane was successfully modified with a more hydrophobic acrylic polymer. This was to produce an insoluble membrane at room temperature where MB reagent could be immobilized to build an optical sensor for carrageenan analysis. The fluorescence intensity of MB in the composite membrane was found to be proportional to the carrageenan concentrations in a linear manner (1.0–20.0 mg L−1, R2 = 0.992) and with a detection limit at 0.4 mg L−1. Recovery of spiked carrageenan into commercial fruit juice products showed percentage recoveries between 90% and 102%. The optical sensor has the advantages of improved sensitivity and better selectivity to carrageenan when compared to other types of hydrocolloids. Its sensitivity was comparable to most sophisticated techniques for carageenan analysis but better than other types of optical sensors. Thus, this sensor provides a simple, rapid, and sensitive means for carageenan analysis.
The Application of Critical Power, the Work Capacity above Critical Power (W′), and Its Reconstitution: A Narrative Review of Current Evidence and Implications for Cycling Training Prescription
Authors: Chorley Alan , Lamb Kevin L.
Published: September 2020

The two-parameter critical power (CP) model is a robust mathematical interpretation of the power–duration relationship, with CP being the rate associated with the maximal aerobic steady state, and W′ the fixed amount of tolerable work above CP available without any recovery. The aim of this narrative review is to describe the CP concept and the methodologies used to assess it, and to summarize the research applying it to intermittent cycle training techniques. CP and W′ are traditionally assessed using a number of constant work rate cycling tests spread over several days. Alternatively, both the 3-min all-out and ramp all-out protocols provide valid measurements of CP and W′ from a single test, thereby enhancing their suitability to athletes and likely reducing errors associated with the assumptions of the CP model. As CP represents the physiological landmark that is the boundary between heavy and severe intensity domains, it presents several advantages over the de facto arbitrarily defined functional threshold power as the basis for cycle training prescription at intensities up to CP. For intensities above CP, precise prescription is not possible based solely on aerobic measures; however, the addition of the W′ parameter does facilitate the prescription of individualized training intensities and durations within the severe intensity domain. Modelling of W′ reconstitution extends this application, although more research is needed to identify the individual parameters that govern W′ reconstitution rates and their kinetics.