bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond Boltzmann–Gibbs–Shannon in Physics and Elsewhere
Authors: Tsallis Constantino
Published: July 2019

The pillars of contemporary theoretical physics are classical mechanics, Maxwell electromagnetism, relativity, quantum mechanics, and Boltzmann–Gibbs (BG) statistical mechanics –including its connection with thermodynamics. The BG theory describes amazingly well the thermal equilibrium of a plethora of so-called simple systems. However, BG statistical mechanics and its basic additive entropy S B G started, in recent decades, to exhibit failures or inadequacies in an increasing number of complex systems. The emergence of such intriguing features became apparent in quantum systems as well, such as black holes and other area-law-like scenarios for the von Neumann entropy. In a different arena, the efficiency of the Shannon entropy—as the BG functional is currently called in engineering and communication theory—started to be perceived as not necessarily optimal in the processing of images (e.g., medical ones) and time series (e.g., economic ones). Such is the case in the presence of generic long-range space correlations, long memory, sub-exponential sensitivity to the initial conditions (hence vanishing largest Lyapunov exponents), and similar features. Finally, we witnessed, during the last two decades, an explosion of asymptotically scale-free complex networks. This wide range of important systems eventually gave support, since 1988, to the generalization of the BG theory. Nonadditive entropies generalizing the BG one and their consequences have been introduced and intensively studied worldwide. The present review focuses on these concepts and their predictions, verifications, and applications in physics and elsewhere. Some selected examples (in quantum information, high- and low-energy physics, low-dimensional nonlinear dynamical systems, earthquakes, turbulence, long-range interacting systems, and scale-free networks) illustrate successful applications. The grounding thermodynamical framework is briefly described as well.
Estimation of FAVAR Models for Incomplete Data with a Kalman Filter for Factors with Observable Components
Authors: Ramsauer Franz , Min Aleksey , Lingauer Michael
Published: July 2019

This article extends the Factor-Augmented Vector Autoregression Model (FAVAR) to mixed-frequency and incomplete panel data. Within the scope of a fully parametric two-step approach, the alternating application of two expectation-maximization algorithms jointly estimates model parameters and missing data. In contrast to the existing literature, we do not require observable factor components to be part of the panel data. For this purpose, we modify the Kalman Filter for factors consisting of latent and observed components, which significantly improves the reconstruction of latent factors according to the performed simulation study. To identify model parameters uniquely, the loadings matrix is constrained. In our empirical application, the presented framework analyzes US data for measuring the effects of the monetary policy on the real economy and financial markets. Here, the consequences for the quarterly Gross Domestic Product (GDP) growth rates are of particular importance.
Probing of Nanoscale Friction and Mechanical Characteristics of Cotton Fiber’s Surface
Authors: Hosseinali Farzad , Thomasson John Alexander
Published: July 2019

The surface topography and nanomechanical attributes of two samples of cotton fibers, namely, A and B, were characterized with various operation modes of an Atomic Force Microscope (AFM). The surface topography and friction images of the fibers were obtained in contact mode. The nanomechanical properties images—i.e., adhesion and deformation—were obtained in force tapping mode. The results indicate that the surface nanomechanical and nanoscale frictional properties of the fibers vary significantly between two samples. The plots of friction versus normal force of the fibers’ surface from both samples are fitted to the equation of single-asperity, adhesion-controlled friction. Nevertheless, within the range of the applied normal force, the friction curves of sample A surfaces show a characteristic transition phase. That is, under low normal forces, the friction curves closely conform with the Hertzian component of friction; after the transition takes place at higher normal forces, the friction curves follow Amontons’ law of friction. We demonstrated that the transition phase corresponds to a state at which the cuticle layer molecules are displaced from the fibers’ surface. The average adhesion force of the samples is consistent with the average friction signal strength collected under low normal forces.
From Apprentice to Master: Casting Men to Play Shakespeare’s Women in Prison
Authors: Dreier Jenna
Published: July 2019

My research investigates the growing phenomenon of Prison Shakespeare—a rapidly expanding community of prison arts programs in which ensembles of men or women who are incarcerated work with outside facilitators to stage performances of Shakespeare. This article is drawn from my first-hand research on Jonathan Shailor’s Shakespeare Prison Project, a program for men who are currently incarcerated at Racine Correctional Institution in Wisconsin. This article is based on my observations of two Shakespeare Prison Project (SPP) rehearsals, their 2017 performance of The Merchant of Venice, and focus groups that I conducted with fifteen members of the ensemble. This article focuses on casting practices and explores the ethical paradox that arises within the hypermasculine environment of men’s prisons, where men cast to play women’s roles face a heightened risk of violence, and yet, where creating positive representations of women is of paramount importance for disrupting the violent misogyny demanded by that hypermasculine environment. Setting SPP in relation to other programs for men, I demonstrate how certain casting practices risk perpetuating toxic masculinities, while others demonstrate the potential to foster alternative masculinities. Based on the insights offered by participants, I argue further that this process is contingent upon the ensemble’s authorization of those alternative masculinities.
Exercise-Based Interventions to Enhance Long-Term Sustainability of Physical Activity in Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Sansano-Nadal Oriol , Giné-Garriga Maria , Brach Jennifer S. , Wert David M. , Jerez-Roig Javier , Guerra-Balic Myriam , Oviedo Guillermo , Fortuño Jesús , Gómara-Toldrà Natàlia , Soto-Bagaria Luis , Pérez Laura Mónica , Inzitari Marco , Solà Ivan , Martin-Borràs Carme , Roqué Marta
Published: July 2019

Exercise is a form of physical activity (PA). PA is an important marker of health and quality of life in older adults. The purpose of this study was to conduct a systematic review of the literature to assess the effect of exercise-based interventions on an at least six-month follow up PA measure, and to describe the specific strategies implemented during the intervention to strengthen the sustainability of PA in community-dwelling 65+ year-old adults. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42017070892) of randomized clinical trials (RCT). We searched three electronic databases during January 2018 to identify RCT assessing any type of exercise-based intervention. Studies had to report a pre-, post-, and at least 6-month post-intervention follow-up. To be included, at least one PA outcome had to be assessed. The effect of exercise-based interventions was assessed compared to active (e.g., a low-intensity type of exercise, such as stretching or toning activities) and non-active (e.g., usual care) control interventions at several time points. Secondary analyses were conducted, restricted to studies that reported specific strategies to enhance the sustainability of PA. The intervention effect was measured on self-reported and objective measures of time spent in PA, by means of standardized mean differences. Standardized mean differences of PA level were pooled. Pooled estimates of effect were computed with the DerSimonian–Laird method, applying a random effects model. The risk of bias was also assessed. We included 12 studies, comparing 18 exercise intervention groups to four active and nine non-active control groups. Nine studies reported specific strategies to enhance the long-term sustainability of PA. The strategies were mostly related to the self-efficacy, self-control, and behavior capability principles based on the social cognitive theory. Exercise interventions compared to active control showed inconclusive and heterogeneous results. When compared to non-active control, exercise interventions improved PA time at the six-months follow up (standardized mean difference (SMD) 0.30; 95%CI 0.15 to 0.44; four studies; 724 participants; I2 0%), but not at the one- or two-years follow-ups. No data were available on the mid- and long-term effect of adding strategies to enhance the sustainability of PA. Exercise interventions have small clinical benefits on PA levels in community-dwelling older adults, with a decline in the observed improvement after six months of the intervention cessation.
A Convolutional Neural Network Architecture for Auto-Detection of Landslide Photographs to Assess Citizen Science and Volunteered Geographic Information Data Quality
Authors: Can Recep , Kocaman Sultan , Gokceoglu Candan
Published: July 2019

Several scientific processes benefit from Citizen Science (CitSci) and VGI (Volunteered Geographical Information) with the help of mobile and geospatial technologies. Studies on landslides can also take advantage of these approaches to a great extent. However, the quality of the collected data by both approaches is often questionable, and automated procedures to check the quality are needed for this purpose. In the present study, a convolutional neural network (CNN) architecture is proposed to validate landslide photos collected by citizens or nonexperts and integrated into a mobile- and web-based GIS environment designed specifically for a landslide CitSci project. The VGG16 has been used as the base model since it allows finetuning, and high performance could be achieved by selecting the best hyper-parameters. Although the training dataset was small, the proposed CNN architecture was found to be effective as it could identify the landslide photos with 94% precision. The accuracy of the results is sufficient for purpose and could even be improved further using a larger amount of training data, which is expected to be obtained with the help of volunteers.
Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway
Authors: Moniruzzaman Md. , Wang Ran , Jeet Varinder , McGuckin Michael A. , Hasnain Sumaira Z.
Published: July 2019

The interleukin (IL)-20 subfamily of cytokines consists of IL-19, IL-20, IL-22, IL-24, and IL-26, and the expression of IL-20, IL-22, and IL-24 is reported to be higher in the colon of patients with ulcerative colitis. Although the receptors for these cytokines are highly expressed in the colon epithelium, their effects on epithelial renewal are not clearly understood. This study evaluated the effects of IL-20, IL-22, and IL-24 in epithelial renewal using the LS174T human colon cancer epithelial cell line. LS174T cells were treated with IL-20, IL-22, and IL-24 (25, 50, and 100 ng/mL) and a live-cell imaging system was used to evaluate the effects on cell proliferation. Following treatment, the signaling pathways contributing to cell proliferation were investigated through Western blotting in LS174T cells and downstream transcriptional changes through qRT-PCR in LS174T cells, and RNA-Seq in primary murine intestinal epithelial cells. Our results demonstrated that only IL-22 promoted LS174T cell proliferation, mediated via extracellular-signal-regulated kinase (ERK)1/2-mediated downstream regulation of p90RSK, c-Jun, and transcriptional changes of TRIM15 and STOM. IL-22 also promoted expression of ERK1/2-independent genes such as DDR2, LCN2, and LRG1, which are known to be involved in cell proliferation and migration. This study suggests that IL-22 induces cell proliferation in highly proliferative cells such as intestinal epithelial cells.
Biomolecules of 2-Thiouracil, 4-Thiouracil and 2,4-Dithiouracil: A DFT Study of the Hydration, Molecular Docking and Effect in DNA:RNAMicrohelixes
Authors: Alcolea Palafox M. , Franklin Benial A. Milton , K. Rastogi V.
Published: July 2019

The molecular structure of 2-thiouracil, 4-thiouracil and 2,4-dithiouracil was analyzed under the effect of the first and second hydration shell by using the B3LYP density functional (DFT) method, and the results were compared to those obtained for the uracil molecule. A slight difference in the water distribution appears in these molecules. On the hydration of these molecules several trends in bond lengths and atomic charges were established. The ring in uracil molecule appears easier to be deformed and adapted to different environments as compared to that when it is thio-substituted. Molecular docking calculations of 2-thiouracil against three different pathogens: Bacillus subtilis, Escherichia coli and Candida albicans were carried out. Docking calculations of 2,4-dithiouracil ligand with various targeted proteins were also performed. Different DNA: RNA hybrid microhelixes with uridine, 2-thiouridine, 4-thiouridine and 2,4-dithiouridine nucleosides were optimized in a simple model with three nucleotide base pairs. Two main types of microhelixes were analyzed in detail depending on the intramolecular H-bond of the 2′-OH group. The weaker Watson–Crick (WC) base pair formed with thio-substituted uracil than with unsubstituted ones slightly deforms the helical and backbone parameters, especially with 2,4-dithiouridine. However, the thio-substitution significantly increases the dipole moment of the A-type microhelixes, as well as the rise and propeller twist parameters.
Novel Tools towards Magnetic Guidance of Neurite Growth: (I) Guidance of Magnetic Nanoparticles into Neurite Extensions of Induced Human Neurons and In Vitro Functionalization with RAS Regulating Proteins
Authors: Schöneborn Hendrik , Raudzus Fabian , Secret Emilie , Otten Nils , Michel Aude , Fresnais Jérome , Ménager Christine , Siaugue Jean-Michel , Zaehres Holm , Dietzel Irmgard D. , Heumann Rolf
Published: July 2019

Parkinson’s disease (PD) is a neurodegenerative disease associated with loss or dysfunction of dopaminergic neurons located in the substantia nigra (SN), and there is no cure available. An emerging new approach for treatment is to transplant human induced dopaminergic neurons directly into the denervated striatal brain target region. Unfortunately, neurons grafted into the substantia nigra are unable to grow axons into the striatum and thus do not allow recovery of the original connectivity. Towards overcoming this general limitation in guided neuronal regeneration, we develop here magnetic nanoparticles functionalized with proteins involved in the regulation of axonal growth. We show covalent binding of constitutive active human rat sarcoma (RAS) proteins or RAS guanine nucleotide exchange factor catalytic domain of son of sevenless (SOS) by fluorescence correlation spectroscopy and multiangle light scattering as well as the characterization of exchange factor activity. Human dopaminergic neurons were differentiated from neural precursor cells and characterized by electrophysiological and immune histochemical methods. Furthermore, we demonstrate magnetic translocation of cytoplasmic γ-Fe2O3@SiO2 core-shell nanoparticles into the neurite extensions of induced human neurons. Altogether, we developed tools towards remote control of directed neurite growth in human dopaminergic neurons. These results may have relevance for future therapeutic approaches of cell replacement therapy in Parkinson’s disease.
Case Study of Dam Overtopping from Waves Generated by Landslides Impinging Perpendicular to a Reservoir’s Longitudinal Axis
Authors: Tessema Netsanet Nigatu , Sigtryggsdóttir Fjóla G. , Lia Leif , Kemal Jabir Asie
Published: July 2019

Landslide-generated impulse waves in dammed reservoirs run up the reservoir banks as well as the upstream dam slope. If large enough, the waves may overtop and even breach the dam and cause flooding of the downstream area with hazardous consequences. Hence, for reservoirs in landslide-prone areas, it is important to provide a means to estimate the potential size of an event triggered by landslides along the reservoir banks. This research deals with landslide-generated waves and the overtopping process over the dam crest in a three-dimensional (3D) physical model test, presenting a case study. The model set-up describes the landslide impacting the reservoir in a perpendicular manner, which is often the case in natural settings. Based on the experimental results, dimensionless empirical relations are derived between the overtopping volume and the governing parameters, namely the slide volume, slide release height, slide impact velocity, still-water depth, and upstream dam face slope. Predictive relations for the overtopping volume are presented as applicable for cases relating to the specific model set-up. Measured overtopping volumes are further compared to a two-dimensional (2D) case reported in the literature. An important feature regarding the overtopping process for the 3D case is the variation in time and space, resulting in an uneven distribution of the volume of water overtopping the dam crest. This observation is made possible by the 3D model set-up, and is of value for dam safety considerations as well as for foundation-related issues, including erosion and scouring.
Study on the Numerical Simulation of the SLM Molten Pool Dynamic Behavior of a Nickel-Based Superalloy on the Workpiece Scale
Authors: Cao Liu , Yuan Xuefeng
Published: July 2019

Nickel-based superalloys are one of the most industrially important families of metallic alloys at present. Selective Laser Melting (SLM), as one of the additive manufacturing technologies for directly forming complex metal parts, has been applied in the production of Inconel 718 components. Based on the more reasonable and comprehensive equivalent processing models (vaporization heat loss, equivalent physical parameters) for the nickel-based superalloy SLM process, an SLM molten pool dynamic behavior prediction model on the workpiece scale was established. Related equivalent processing models were customized by secondary development with the software Fluent. In order to verify the feasibility of the SLM molten pool dynamics model, the SLM single-pass employed to form the Inconel 718 alloy process was calculated. The simulated and experimental solidified track dimensions were in good agreement. Then, the influences of different process parameters (laser power, scanning speed) on the SLM formation of the Inconel 718 alloy were calculated and analyzed. The simulation and experimental solidified track widths were well-matched, and the result showed that, as a rule, the solidified track width increased linearly with the laser power and decreased linearly with the scanning speed. This paper will help lay the foundation for a subsequent numerical simulation study of the thermal-melt-stress evolution process of an SLM workpiece.
Human Papillomavirus and Infertility
Authors: Jeršovienė Vilma , Gudlevičienė Živilė , Rimienė Jolita , Butkauskas Dalius
Published: July 2019

Background and objectives. Human papillomavirus (HPV) is the most commonly sexually transmitted infection. Recent evidence suggests that an HPV infection may affect fertility. The aim of the study was to determine the prevalence of HPV infections among couples undergoing in vitro fertilization (IVF) and to identify their awareness of HPV. Material and Methods. A total of 200 samples were collected from couples who received IVF treatment during 2017–2018 in Vilnius University Hospital Santaros Klinikos (VUH SK) Santaros Fertility Centre (SFC). For HPV detection, cervical swabs from women and sperm samples from men were taken and a real time polymerase chain reaction (RT-PCR) was used for the identification of 14 high-risk HPV types. Sperm parameters were evaluated according to World Health Organization (WHO) recommendations for 2010. Research subjects answered an anonymous questionnaire to ascertain their knowledge of HPV. Results. After testing of HPV in couples undergoing IVF, it was found that 33 out of 100 couples (33%) were HPV positive. Of these, 19% of women (19/100) and 20% of men (20/100) tested positive. Using Fisher’s exact test, a statistically significant difference was found between HPV infections and abnormal sperm quality parameters (p = 0.023). Conclusions. HPV may have an impact in spermatogenesis, because an HPV infection was more frequently detected in men with abnormal sperm parameters. High-risk HPV 52 was the most common genotype among couples undergoing IVF treatment.
Patterned Metal/Polymer Strain Sensor with Good Flexibility, Mechanical Stability and Repeatability for Human Motion Detection
Authors: Zheng Xu , Wang Qing , Luan Jinjin , Li Yao , Wang Ning
Published: July 2019

Wearable health monitoring smart systems based on flexible metal films are considered to be the next generation of devices for remote medical practice. However, cracks on the metallic surface of the films and difficulty in repeatability are the key issues that restrict the application of such wearable strain sensors. In this work, a flexible wearable strain sensor with high sensitivity and good repeatability was fabricated based on a patterned metal/polymer composite material fabricated through nanoimprint lithography. The mechanical properties were measured through cyclic tension and bending loading. The sensor exhibited a small ΔR/R0 error line for multiple test pieces, indicating the good mechanical stability and repeatability of the fabricated device. Moreover, the sensor possesses high sensitivity with gauge factors of 10 for strain less than 50% and 40 for strain from 50% to 70%. Various activities were successfully detected in real-time, such as swallowing, closing/opening of the mouth, and multi-angle bending of elbow, which illustrates the proposed sensor’s potential as a wearable device for the human body.
A Histone Acetyltransferase Inhibitor with Antifungal Activity against CTG clade Candida Species
Authors: Tscherner Michael , Kuchler Karl
Published: July 2019

Candida species represent one of the most frequent causes of hospital-acquired infections in immunocompromised patient cohorts. Due to a very limited set of antifungals available and an increasing prevalence of drug resistance, the discovery of novel antifungal targets is essential. Targeting chromatin modifiers as potential antifungal targets has gained attention recently, mainly due to their role in regulating virulence in Candida species. Here, we describe a novel activity for the histone acetyltransferase inhibitor Cyclopentylidene-[4-(4-chlorophenyl)thiazol-2-yl)hydrazone (CPTH2) as a specific inhibitor of CTG clade Candida species. Furthermore, we show that CPTH2 has fungicidal activity and protects macrophages from Candida-mediated death. Thus, this work could provide a starting point for the development of novel antifungals specific to CTG clade Candida species.
Electrochemical, Spectroscopic, and Computational Investigations on Redox Reactions of Selenium Species on Galena Surfaces
Authors: Cook Peter , Kim YoungJae , Yuan Ke , Marcano Maria C. , Becker Udo
Published: July 2019

Despite previous studies investigating selenium (Se) redox reactions in the presence of semiconducting minerals, Se redox reactions mediated by galena (PbS) are poorly understood. In this study, the redox chemistry of Se on galena is investigated over a range of environmentally relevant Eh and pH conditions (+0.3 to −0.6 V vs. standard hydrogen electrode, SHE; pH 4.6) using a combination of electrochemical, spectroscopic, and computational approaches. Cyclic voltammetry (CV) measurements reveal one anodic/cathodic peak pair at a midpoint potential of +30 mV (vs. SHE) that represents reduction and oxidation between HSeO3− and H2Se/HSe−. Two peak pairs with midpoint potentials of −400 and −520 mV represent the redox transformation from Se(0) to HSe− and H2Se species, respectively. The changes in Gibbs free energies of adsorption of Se species on galena surfaces as a function of Se oxidation state were modeled using quantum-mechanical calculations and the resulting electrochemical peak shifts are (−0.17 eV for HSeO3−/H2Se, −0.07 eV for HSeO3−/HSe−, 0.15 eV for Se(0)/HSe−, and −0.15 eV for Se(0)/H2Se). These shifts explain deviation between Nernstian equilibrium redox potentials and observed midpoint potentials. X-ray photoelectron spectroscopy (XPS) analysis reveals the formation of Se(0) potentials below −100 mV and Se(0) and Se(−II) species at potentials below −400 mV.
Enantioselective Synthesis of Chromanones Bearing an α,α-Disubstituted α-Amino Acid Moiety via Decarboxylative Michael Reaction
Authors: Bojanowski Jan , Sieroń Lesław , Albrecht Anna
Published: July 2019

In this manuscript, a novel, decarboxylative Michael reaction between α-substituted azlactones and chromone-3-carboxylic acids is described. The reaction proceeds in a sequence Michael addition followed by decarboxylative deprotonation, and it results in the formation of chromanones bearing an azlactone structural unit. The possibility of transforming an azlactone moiety into a protected α,α-disubstituted α-amino acid derivative is also demonstrated.
Preparation of Nanoemulsions of Vitamin A and C by Microfluidization: Efficacy on the Expression Pattern of Milk-Specific Proteins in MAC-T Cells
Authors: Kim Tae-Il , Kim Tae-Gyun , Lim Dong-Hyun , Kim Sang-Bum , Park Seong-Min , Hur Tai-Young , Ki Kwang-Seok , Kwon Eung-Gi , Vijayakumar Mayakrishnan , Kim Young-Jun
Published: July 2019

In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit-A) and C (vit-C) were prepared using Lipoid S 75 and microfluidization. The particle size and polydispersity index (PDI) of nanoemulsified vit-A and vit-C were studied. The cytotoxic effect of nanoemulsion-free and nanoemulsified vit-A and vit-C was determined by an MTT assay. In addition, the efficacy of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was investigated by quantitative RT-PCR. The results showed that the efficacies of stabilized nanoemulsions of vit-A and vit-C were 100% and 92.7%, respectively. The particle sizes were around 475.7 and 225.4 nm, and the zeta potentials were around −33.5 and −21.3 mV, respectively. The expression changes of αs2-, β- and κ-casein were higher in the presence of a stabilized nanoemulsion of vit-A, compared with nanoemulsion-free vit-A. Furthermore, the expression changes of αs2- and β-casein were lower and that of κ-casein was higher in the presence of a stabilized nanoemulsion of vit-C, compared with nanoemulsion-free vit-C. Thus, our findings demonstrate the efficacy of nanoemulsified vit-A and vit-C in changing the expression of milk-specific proteins in MAC-T cells.
In Silico Repositioning of Cannabigerol as a Novel Inhibitor of the Enoyl Acyl Carrier Protein (ACP) Reductase (InhA)
Authors: Pinzi Luca , Lherbet Christian , Baltas Michel , Pellati Federica , Rastelli Giulio
Published: July 2019

Cannabigerol (CBG) and cannabichromene (CBC) are non-psychoactive cannabinoids that have raised increasing interest in recent years. These compounds exhibit good tolerability and low toxicity, representing promising candidates for drug repositioning. To identify novel potential therapeutic targets for CBG and CBC, an integrated ligand-based and structure-based study was performed. The results of the analysis led to the identification of CBG as a low micromolar inhibitor of the Enoyl acyl carrier protein (ACP) reductase (InhA) enzyme.
Discovery of New Selective Butyrylcholinesterase (BChE) Inhibitors with Anti-Aβ Aggregation Activity: Structure-Based Virtual Screening, Hit Optimization and Biological Evaluation
Authors: Jiang Cheng-Shi , Ge Yong-Xi , Cheng Zhi-Qiang , Wang Yin-Yin , Tao Hong-Rui , Zhu Kongkai , Zhang Hua
Published: July 2019

In this study, a series of selective butyrylcholinesterase (BChE) inhibitors was designed and synthesized from the structural optimization of hit 1, a 4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzoic acid derivative identified by virtual screening our compound library. The in vitro enzyme assay results showed that compounds 9 ((4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)phenyl)(pyrrolidin-1-yl)methanone) and 23 (N-(2-bromophenyl)-4-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)benzamide) displayed improved BChE inhibitory activity and good selectivity towards BChE versus AChE. Their binding modes were probed by molecular docking and further validated by molecular dynamics simulation. Kinetic analysis together with molecular modeling studies suggested that these derivatives could target both the catalytic active site (CAS) and peripheral anionic site (PAS) of BChE. In addition, the selected compounds 9 and 23 displayed anti-Aβ1–42 aggregation activity in a dose-dependent manner, and they did not show obvious cytotoxicity towards SH-SY5Y neuroblastoma cells. Also, both compounds showed significantly protective activity against Aβ1-42-induced toxicity in a SH-SY5Y cell model. The present results provided a new valuable chemical template for the development of selective BChE inhibitors.
Taste Evaluation of Yellowtail (Seriola Quinqueradiata) Ordinary and Dark Muscle by Metabolic Profiling
Authors: Mabuchi Ryota , Ishimaru Ayaka , Adachi Miwako , Zhao Huiqing , Kikutani Haruka , Tanimoto Shota
Published: July 2019

We performed metabolic profiling on yellowtail (Seriola quinqueradiata) muscle to develop an objective taste evaluation method for fish meat. Dark (DM) and ordinary (OM) muscle samples before and after storage were subjected to gas chromatography-mass spectrometry (GC-MS) analysis and taste measurements using an electronic tongue. The metabolites identified by the GC-MS analysis were treated as x variables, and the taste values obtained by the electronic tongue were treated as y variables. The relationships between the metabolites and taste attributes were evaluated by two-way orthogonal projections to latent structures (O2PLS) analysis. The O2PLS analyses were normalized in two ways, unit variance (UV) and pareto (Par) scaling. The O2PLS (UV) analysis produced 3+1+0 models in Autofit and this model was statistically significant with R2Y (0.73) and Q2 (0.52) metrics. In particular, significant correlations were found between DM or OM and metabolite intensity and taste attributes, and strong associations were found between “sourness” and lysine, “irritant” and alanine and phenylalanine, “saltiness” and pantothenic acid, and “umami” and creatinine and histidine. The O2PLS (Par) analysis of DM generated significant predictive models for “acidic bitterness,” “irritant,” “saltiness,” “bitterness,” “astringency,” and “richness.” Among these, only “irritant” was affected by storage. This method was thus effective in evaluating the taste of yellowtail muscle.
Antimicrobial and Phytotoxic Activity of Origanum heracleoticum and O. majorana Essential Oils Growing in Cilento (Southern Italy)
Authors: Della Pepa Teresa , Elshafie Hazem S. , Capasso Raffaele , De Feo Vincenzo , Camele Ippolito , Nazzaro Filomena , Scognamiglio Maria Rosa , Caputo Lucia
Published: July 2019

There is a growing interest in a potential use of essential oils (EOs) as a replacement for traditional pesticides and herbicides. The aims of this study were to: (i) Identify the chemical composition of the two EOs derived from Origanum heracleoticum L. and O. majorana L., (ii) evaluate the in vitro antifungal activity of the EOs against some postharvest phytopathogens (Botrytis cinerea, Penicillium expansum, Aspergillus niger and Monilinia fructicola), (iii) evaluate the in vitro antibacterial activity against Bacillus megaterium, Clavibacter michiganensis, Xanthomonas campestris, Pseudomonas fluorescens and P. syringae pv. phaseolicola, (iv) evaluate the effect of both studied EOs on the spore germination percentage and their minimum inhibitory concentration (MIC) against M. fructicola, and (v) study the possible phytotoxicity of the two EOs and their major constituents, carvacrol for O. heracleoticum and terpinen-4-ol for O. majorana, against tha germination and initial radicle growth of radish, lettuce, garden cress and tomato. The two EOs demonstrated promising in vitro antimicrobial and antifungal activities against all tested microorganisms. EOs showed high inhibition of spore germination percentage at the minimal inhibitory concentration of 500 and 2000 µg/mL, respectively. Moreover, both germination and radical elongation of selected plant species were sensitive to the oils.
Effect of Staple Age on DNA Origami Nanostructure Assembly and Stability
Authors: Kielar Charlotte , Xin Yang , Xu Xiaodan , Zhu Siqi , Gorin Nelli , Grundmeier Guido , Möser Christin , Smith David M. , Keller Adrian
Published: July 2019

DNA origami nanostructures are widely employed in various areas of fundamental and applied research. Due to the tremendous success of the DNA origami technique in the academic field, considerable efforts currently aim at the translation of this technology from a laboratory setting to real-world applications, such as nanoelectronics, drug delivery, and biosensing. While many of these real-world applications rely on an intact DNA origami shape, they often also subject the DNA origami nanostructures to rather harsh and potentially damaging environmental and processing conditions. Furthermore, in the context of DNA origami mass production, the long-term storage of DNA origami nanostructures or their pre-assembled components also becomes an issue of high relevance, especially regarding the possible negative effects on DNA origami structural integrity. Thus, we investigated the effect of staple age on the self-assembly and stability of DNA origami nanostructures using atomic force microscopy. Different harsh processing conditions were simulated by applying different sample preparation protocols. Our results show that staple solutions may be stored at −20 °C for several years without impeding DNA origami self-assembly. Depending on DNA origami shape and superstructure, however, staple age may have negative effects on DNA origami stability under harsh treatment conditions. Mass spectrometry analysis of the aged staple mixtures revealed no signs of staple fragmentation. We, therefore, attribute the increased DNA origami sensitivity toward environmental conditions to an accumulation of damaged nucleobases, which undergo weaker base-pairing interactions and thus lead to reduced duplex stability.
More Research Is Necessary to Establish the Ergogenic Effect of Caffeine in Female Athletes
Authors: Salinero Juan José , Lara Beatriz , Jiménez-Ormeño Ester , Romero-Moraleda Blanca , Giráldez-Costas Verónica , Baltazar-Martins Gabriel , Del Coso Juan
Published: July 2019

Dear Editor-in-Chief, [...]
Breastfeeding Status and Duration and Infections, Hospitalizations for Infections, and Antibiotic Use in the First Two Years of Life in the ELFE Cohort
Authors: Davisse-Paturet Camille , Adel-Patient Karine , Divaret-Chauveau Amandine , Pierson Juliette , Lioret Sandrine , Cheminat Marie , Dufourg Marie-Noëlle , Charles Marie-Aline , de Lauzon-Guillain Blandine
Published: July 2019

In low- and middle-income countries, the protective effect of breastfeeding against infections is well established, but in high-income countries, the effect could be weakened by higher hygienic conditions. We aimed to examine the association between breastfeeding and infections in the first 2 years of life, in a high-income country with relatively short breastfeeding duration. Among 10,349 young children from the nationwide Etude Longitudinale Française depuis l’Enfance (ELFE) birth cohort, breastfeeding and parent-reported hospitalizations, bronchiolitis and otitis events, and antibiotic use were prospectively collected up to 2 years. Never-breastfed infants were used as reference group. Any breastfeeding for <3 months was associated with higher risks of hospitalizations from gastrointestinal infections or fever. Predominant breastfeeding for <1 month was associated with higher risk of a single hospital admission while predominant breastfeeding for ≥3 months was associated with a lower risk of long duration (≥4 nights) of hospitalization. Ever breastfeeding was associated with lower risk of antibiotic use. This study confirmed the well-known associations between breastfeeding and hospitalizations but also highlighted a strong inverse association between breastfeeding and antibiotic use. Although we cannot infer causality from this observational study, this finding is worth highlighting in a context of rising concern regarding antibiotic resistance.
Ionic Polymethacrylate Based Delivery Systems: Effect of Carrier Topology and Drug Loading
Authors: Neugebauer Dorota , Mielańczyk Anna , Bielas Rafał , Odrobińska Justyna , Kupczak Maria , Niesyto Katarzyna
Published: July 2019

The presented drug delivery polymeric systems (DDS), i.e., conjugates and self-assemblies, based on grafted and star-shaped polymethacrylates have been studied for the last few years in our group. This minireview is focused on the relationship of polymer structure to drug conjugation/entrapment efficiency and release capability. Both graft and linear polymers containing trimethylammonium groups showed the ability to release the pharmaceutical anions by ionic exchange, but in aqueous solution they were also self-assembled into nanoparticles with encapsulated nonionic drugs. Star-shaped polymers functionalized with ionizable amine/carboxylic groups were investigated for drug conjugation via ketimine/amide linkers. However, only the conjugates of polybases were water-soluble, giving opportunity for release studies, whereas the self-assembling polyacidic stars were encapsulated with the model drugs. Depending on the type of drug loading in the polymer matrix, their release rates were ordered as follows: Physical ≥ ionic > covalent. The studies indicated that the well-defined ionic polymethacrylates, including poly(ionic liquid)s, are advantageous for designing macromolecular carriers due to the variety of structural parameters, which are efficient for tuning of drug loading and release behavior in respect to the specific drug interactions.
Transmucosal Absorption Enhancers in the Drug Delivery Field
Authors: Maher Sam , Casettari Luca , Illum Lisbeth
Published: July 2019

Drug delivery systems that safely and consistently improve transport of poorly absorbed compounds across epithelial barriers are highly sought within the drug delivery field. The use of chemical permeation enhancers is one of the simplest and widely tested approaches to improve transmucosal permeability via oral, nasal, buccal, ocular and pulmonary routes. To date, only a small number of permeation enhancers have progressed to clinical trials, and only one product that includes a permeation enhancer has reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Transmucosal Absorption Enhancers in the Drug Delivery Field (https://www.mdpi.com/journal/pharmaceutics/special_issues/transmucosal_absorption_enhancers). The guest editors outline the scope of the issue, reflect on the results and the conclusions of the 19 articles published in the issue and provide an outlook on the use of permeation enhancers in the drug delivery field.
Control of Organ Abscission and Other Cell Separation Processes by Evolutionary Conserved Peptide Signaling
Authors: Shi Chun-Lin , Alling Renate Marie , Hammerstad Marta , Aalen Reidunn B.
Published: July 2019

Plants both generate and shed organs throughout their lifetime. Cell separation is in function during opening of anthers to release pollen; floral organs are detached after pollination when they have served their purpose; unfertilized flowers are shed; fruits and seeds are abscised from the mother plant to secure the propagation of new generations. Organ abscission takes place in specialized abscission zone (AZ) cells where the middle lamella between adjacent cell files is broken down. The plant hormone ethylene has a well-documented promoting effect on abscission, but mutation in ethylene receptor genes in Arabidopsis thaliana only delays the abscission process. Microarray and RNA sequencing have identified a large number of genes differentially expressed in the AZs, especially genes encoding enzymes involved in cell wall remodelling and disassembly. Mutations in such genes rarely give a phenotype, most likely due to functional redundancy. In contrast, mutation in the INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) blocks floral organ abscission in Arabidopsis. IDA encodes a small peptide that signals through the leucine-rich repeat receptor-like kinases HAESA (HAE) and HAE-LIKE2 (HSL2) to control floral organ abscission and facilitate lateral root emergence. Untimely abscission is a severe problem in many crops, and in a more applied perspective, it is of interest to investigate whether IDA-HAE/HSL2 is involved in other cell separation processes and other species. Genes encoding IDA and HSL2 orthologues have been identified in all orders of flowering plants. Angiosperms have had enormous success, with species adapted to all kinds of environments, adaptations which include variation with respect to which organs they shed. Here we review, from an evolutionary perspective, the properties of the IDA-HAE/HSL2 signaling module and the evidence for its hypothesized involvement in various cell separation processes in angiosperms.
Integration of Phenotype and Hormone Data during Adventitious Rooting in Carnation (Dianthus caryophyllus L.) Stem Cuttings
Authors: Justamante María Salud , Acosta-Motos José Ramón , Cano Antonio , Villanova Joan , Birlanga Virginia , Albacete Alfonso , Cano Emilio Á. , Acosta Manuel , Pérez-Pérez José Manuel
Published: July 2019

The rooting of stem cuttings is a highly efficient procedure for the vegetative propagation of ornamental plants. In cultivated carnations, an increased auxin level in the stem cutting base produced by active auxin transport from the leaves triggers adventitious root (AR) formation from the cambium. To provide additional insight into the physiological and genetic basis of this complex trait, we studied AR formation in a collection of 159 F1 lines derived from a cross between two hybrid cultivars (2003 R 8 and 2101-02 MFR) showing contrasting rooting performances. In three different experiments, time-series for several stem and root architectural traits were quantified in detail in a subset of these double-cross hybrid lines displaying extreme rooting phenotypes and their parental genotypes. Our results indicate that the water content and area of the AR system directly contributed to the shoot water content and shoot growth. Moreover, morphometric data and rooting quality parameters were found to be associated with some stress-related metabolites such as 1-aminocyclopropane-1-carboxylic acid (ACC), the ethylene precursor, and the conjugated auxin indol-3-acetic acid-aspartic acid (IAA-Asp).
Exploring the Potential of Religious Literacy in Pakistani Education
Authors: Ashraf Muhammad Azeem
Published: July 2019

Religious education is a compulsory subject in Pakistani schools in which students learn basic knowledge about Islam without exploring the sectarian differences between each sect of Islam. The division of Muslims into Sunni and Shia and the further division of Sunni Muslims into different sects has caused massive sectarian violence in Pakistan. This study uses qualitative methods to explore the possibility of engaging with religious literacy and religious education to explain the purpose, contents, and practical application of religious education and to mitigate existing challenges linked to religion in Pakistan. Even though religious education does not support sectarian differences, individual opinions about sectarian differences are still a major component of divisiveness in Pakistani society. Through interviews with 25 teachers from different levels of education (six primary school teachers, five high school teachers, five college teachers, five university teachers, and four religious school teachers), in this article, I argue that teachers of religious education in schools are neither following a common faith in teaching religious education nor are they in full agreement on providing equal rights to all students of different religious beliefs. Rather, most believe in their personal ideology centered on their own particular religious sect that largely rejects the concept of religious literacy. There is a need for evaluation and improvement of the teaching and learning of religion in schools in order to explain misperceptions about its practical application as well as to engage religious education with diversity.
Characterizing Land Use/Land Cover Using Multi-Sensor Time Series from the Perspective of Land Surface Phenology
Authors: Nguyen Lan H. , Henebry Geoffrey M.
Published: July 2019

Due to a rapid increase in accessible Earth observation data coupled with high computing and storage capabilities, multiple efforts over the past few years have aimed to map land use/land cover using image time series with promising outcomes. Here, we evaluate the comparative performance of alternative land cover classifications generated by using only (1) phenological metrics derived from either of two land surface phenology models, or (2) a suite of spectral band percentiles and normalized ratios (spectral variables), or (3) a combination of phenological metrics and spectral variables. First, several annual time series of remotely sensed data were assembled: Accumulated growing degree-days (AGDD) from the MODerate resolution Imaging Spectroradiometer (MODIS) 8-day land surface temperature products, 2-band Enhanced Vegetation Index (EVI2), and the spectral variables from the Harmonized Landsat Sentinel-2, as well as from the U.S. Landsat Analysis Ready Data surface reflectance products. Then, at each pixel, EVI2 time series were fitted using two different land surface phenology models: The Convex Quadratic model (CxQ), in which EVI2 = f(AGDD) and the Hybrid Piecewise Logistic Model (HPLM), in which EVI2 = f(day of year). Phenometrics and spectral variables were submitted separately and together to Random Forest Classifiers (RFC) to depict land use/land cover in Roberts County, South Dakota. HPLM RFC models showed slightly better accuracy than CxQ RFC models (about 1% relative higher in overall accuracy). Compared to phenometrically-based RFC models, spectrally-based RFC models yielded more accurate land cover maps, especially for non-crop cover types. However, the RFC models built from spectral variables could not accurately classify the wheat class, which contained mostly spring wheat with some fields in durum or winter varieties. The most accurate RFC models were obtained when using both phenometrics and spectral variables as inputs. The combined-variable RFC models overcame weaknesses of both phenometrically-based classification (low accuracy for non-vegetated covers) and spectrally-based classification (low accuracy for wheat). The analysis of important variables indicated that land cover classification for this study area was strongly driven by variables related to the initial green-up phase of seasonal growth and maximum fitted EVI2. For a deeper evaluation of RFC performance, RFC classifications were also executed with several alternative sampling scenarios, including different spatiotemporal filters to improve accuracy of sample pools and different sample sizes. Results indicated that a sample pool with less filtering yielded the most accurate predicted land cover map and a stratified random sample dataset covering approximately 0.25% or more of the study area were required to achieve an accurate land cover map. In case of data scarcity, a smaller dataset might be acceptable, but should not smaller than 0.05% of the study area.