bluuebunny/crossref_metadata_2025 huggingface dataset:
U–Pb Geochronology of Hydrothermal Monazite from Uraniferous Greisen Veins Associated with the High Heat Production Mount Douglas Granite, New Brunswick, Canada
Authors: Mohammadi Nadia , McFarlane Christopher R. M. , Lentz David R.
Published: May 2019

A combination of in situ laser ablation inductively coupled plasma–mass spectrometry (LA ICP–MS) analyses guided by Scanning Electron Microscope–Back-Scattered Electron imaging (SEM–BSE) was applied to hydrothermal monazite from greisen veins of the Late Devonian, highly evolved, uraniferous Mount Douglas Granite, New Brunswick, Canada. Understanding the uraniferous nature of the suite and characterizing the hydrothermal system that produced the associated mineralized greisen veins were the main goals of this study. The uraniferous nature of the Mount Douglas Granite is evident from previous airborne radiometric surveys, whole-rock geochemical data indicating high U and Th (2–22 ppm U; 19–71 ppm Th), the presence of monazite, zircon, xenotime, thorite, bastnaesite, and uraninite within the pluton and the associated hydrothermal greisen veins, as well as anomalous levels of U and Th in wolframite, hematite, and martite within greisen veins. New U–Pb geochronology of hydrothermal monazite coexisting with sulfide and oxide minerals yielded mineralization ages ranging from 344 to 368 Ma, with most of them (90%) younger than the crystallization age of the pluton (368 ± 3 Ma). The younger mineralization age indicates post-magmatic hydrothermal activities within the Mount Douglas system that was responsible for the mineralization. The production of uraniferous greisen veins by this process is probably associated with the High Heat Production (HHP) nature of this pluton, resulting from the radioactive decay of U, Th, and K. This heat prolongs post-crystallization hydrothermal fluid circulation and promotes the generation of hydrothermal ore deposits that are younger than the pluton. Assuming a density of 2.61 g/cm3, the average weighted mean radiogenic heat production of the Mount Douglas granites is 5.9 µW/m3 (14.1 HGU; Heat Generation Unit), in which it ranges from 2.2 µW/m3 in the least evolved unit, Dmd1, up to 10.1 µW/m3 in the most fractionated unit, Dmd3. They are all significantly higher than the average upper continental crust (1.65 µW/m3). The high radiogenic heat production of the Mount Douglas Granite, accompanied by a high estimated heat flow of 70 mW/m2, supports the assignment of the granite to a ‘hot crust’ (>7 HGU) HHP granite and highlights its potential for geothermal energy exploration.
A Comprehensive Overview of Polypharmacy in Elderly Patients in Saudi Arabia
Authors: Alsuwaidan Aseel , Almedlej Norah , Alsabti Sawsan , Daftardar Omamah , Al Deaji Fawzi , Al Amri Ali , Alsuwaidan Salem
Published: May 2019

Background/Objectives: Saudi Arabia has a great percentage of geriatric patients associated with multiple chronic diseases who require close attention and monitoring for their medications. The purpose of this study is to develop a full-framed picture about the utilization of medications for geriatric patients and how to provide better health-care management. Methodology: A retrospective cross-sectional study targeting patients 65 years of age and older, who are taking multiple chronic medications for different indications. Descriptive analysis and frequency of the main variables were used as appropriate. Only qualified and professional candidates were chosen for data entry to present the quality and accuracy of data. Results: A total of 3009 patient profiles were analyzed, with the patients’ average age in years being 73.26 ± 6.6 (SD). It was found that 55% of the patients have polypharmacy. An average of 6.4 medications were prescribed for patients aged between 65 and 70 years compared with a significant difference for patients aged 71 years and above, while a linear correlation between age and comorbidity diseases associated with all elderly patients. Hypertension, hyperlipidemia, and diabetes mellitus are the most common comorbidity diseases for elderly patients aged 65 years and older. Conclusion: Polypharmacy in geriatrics is defined as a patient aged 65 years and older receiving five or more appropriate medications. It is the responsibility of health-care professionals to reduce the number of medications in elderly patients. Awareness of geriatric medications and diagnosed diseases will improve managing adverse drug reaction and other risk factors. Awareness of geriatric medications should elaborate on how to avoid adverse drug reaction and other risk factors. It is the responsibility of physicians and pharmacists to reduce the number of medications in elderly patients. We also prove that the number of medications will not necessarily increase with age. The main impact of this study is to follow the main recommendations to improve health care management in geriatrics.
Music of the Tabom: An Emblem of Identity
Authors: Amakye-Boateng Benjamin
Published: May 2019

This paper discusses how music functions as an emblem of identity for the Afro-Brazilian community in Accra, Ghana, known as the Tabom. The paper provides a contextual and analytical study of the complete musical enactment as practiced by this community, and argues, that the Tabom musical genre, known as Agbe, serves the purpose of creating and negotiating identity as found in their use of music within Tabom socio-cultural, religious, and political ceremonies. In this paper, I argue that Agbe is not only an organized sound in Tabom culture, but rather, it is one of the strongest cultural elements that serves as an emblem of identity relating to the life and culture of the Tabom community in Accra. Relying on ethnographic research design, Agbe is presented as the focus of study, subjecting the context in which it is performed to study and analysis. Moreover, the relationships between the Agbe ensemble and their performance context, as well as live events are discussed with the intent of conveying meanings of singing, drumming, dancing, and other related artistic expressions as they all contribute to help the Tabom to negotiate their identity.
Use of the Phase-Based Model of Smoking Treatment to Guide Intervention Development for Persons Living with HIV Who Self-Identify as African American Tobacco Smokers
Authors: Schnall Rebecca , Carcamo Jasmine , Porras Tiffany , Huang Ming-Chun , Webb Hooper Monica
Published: May 2019

Cigarette smoking is highly prevalent among persons living with the human immunodeficiency virus (HIV) (PLWH), with rates as high 50% as compared to 14% in the general U.S. population. Tobacco use causes morbidity and mortality in PLWH, and tobacco-related harm is substantially higher in PLWH than smokers in the general population, providing the scientific premise for developing effective tobacco cessation interventions in this population. To better address this issue, we conducted six focus group sessions with 45 African American smokers who are living with HIV to understand the barriers to smoking cessation and the strategies that would be helpful to overcome these barriers. We organized our findings by the Phase-Based Model of Smoking Treatment to understand the intervention components that are needed at each phase to help PLWH successfully quit smoking. Participants in our focus group sessions articulated key components for incorporation into tobacco cessation intervention for PLWH: a personalized plan for quitting, reminders about that plan, and a support system. Participants thought that their HIV and tobacco use were disassociated. Participants described barriers to the use of pharmacotherapy, including adverse side effects of the gum and patch and concerns about the negative health effects of some oral medications. Substance use was identified as a commonly co-occurring condition as well as a barrier to successfully ceasing to smoke tobacco products. In summary, these findings offer information on the components of a tobacco cessation intervention for PLWH, namely reminders, a support system, substance use treatment, and monitoring to prevent relapse.
In Silico Study of the Resistance to Organophosphorus Pesticides Associated with Point Mutations in Acetylcholinesterase of Lepidoptera: B. mandarina, B. mori, C. auricilius, C. suppressalis, C. pomonella, H. armígera, P. xylostella, S. frugiperda, and S. litura
Authors: Reyes-Espinosa Francisco , Méndez-Álvarez Domingo , Pérez-Rodríguez Miguel A. , Herrera-Mayorga Verónica , Juárez-Saldivar Alfredo , Cruz-Hernández María A. , Rivera Gildardo
Published: May 2019

An in silico analysis of the interaction between the complex-ligands of nine acetylcholinesterase (AChE) structures of Lepidopteran organisms and 43 organophosphorus (OPs) pesticides with previous resistance reports was carried out. To predict the potential resistance by structural modifications in Lepidoptera insects, due to proposed point mutations in AChE, a broad analysis was performed using computational tools, such as homology modeling and molecular docking. Two relevant findings were revealed: (1) Docking results give a configuration of the most probable spatial orientation of two interacting molecules (AChE enzyme and OP pesticide) and (2) a predicted ΔGb. The mutations evaluated in the form 1 acetylcholinesterase (AChE-1) and form 2 acetylcholinesterase (AChE-2) structures of enzymes do not affect in any way (there is no regularity of change or significant deviations) the values of the binding energy (ΔGb) recorded in the AChE–OPs complexes. However, the mutations analyzed in AChE are associated with a structural modification that causes an inadequate interaction to complete the phosphorylation of the enzyme.
Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System
Authors: Fichi Gianluca , Naef Valentina , Barca Amilcare , Longo Giovanna , Fronte Baldassare , Verri Tiziano , Santorelli Filippo M. , Marchese Maria , Petruzzella Vittoria
Published: May 2019

The zebrafish (Danio rerio) is a small vertebrate ideally suited to the modeling of human diseases. Large numbers of genetic alterations have now been modeled and could be used to study organ development by means of a genetic approach. To date, limited attention has been paid to the possible use of the zebrafish toolbox in studying human mitochondrial disorders affecting the nervous system. Here, we review the pertinent scientific literature discussing the use of zebrafish in modeling gene mutations involved in mitochondria-related neurological human diseases. A critical analysis of the literature suggests that the zebrafish not only lends itself to exploration of the pathological consequences of mitochondrial energy output on the nervous system but could also serve as an attractive platform for future drugs in an as yet untreatable category of human disorders.
Computational Studies on Water-Catalyzed Mechanisms for Stereoinversion of Glutarimide Intermediates Formed from Glutamic Acid Residues in Aqueous Phase
Authors: Nakayoshi Tomoki , Fukuyoshi Shuichi , Kato Koichi , Kurimoto Eiji , Oda Akifumi
Published: May 2019

Aspartic acid (Asp) residues are prone to non-enzymatic stereoinversion, and Asp-residue stereoinversion is believed to be mediated via a succinimide (SI) intermediate. The stereoinverted Asp residues are believed to cause several age-related diseases. However, in peptides and proteins, few studies have reported the stereoinversion of glutamic acid (Glu) residues whose structures are similar to that of Asp. We previously presumed that Glu-residue stereoinversion proceeds via a glutarimide (GI) intermediate and showed that the calculated activation barriers of SI- and GI-intermediate stereoinversion are almost equivalent in the gas phase. In this study, we investigated the stereoinversion pathways of the l-GI intermediate in the aqueous phase using B3LYP density functional methods. The calculated activation barrier of l-GI-intermediate stereoinversion in the aqueous phase was approximately 36 kcal·mol−1, which was much higher than that in the gas phase. Additionally, as this activation barrier exceeded that of Asp-residue stereoinversion, it is presumed that Glu-residue stereoinversion has a lower probability of proceeding under physiological conditions than Asp-residue stereoinversion.
The 40S Ribosomal Protein S6 Response to Blue Light by Interaction with SjAUREO in Saccharina japonica
Authors: Luan Hexiang , Yao Jianting , Chen Zhihang , Duan Delin
Published: May 2019

Blue light (BL) plays an important role in regulation of the growth and development of aquatic plants and land plants. Aureochrome (AUREO), the recent BL photoreceptor identified in photosynthetic stramenopile algae, is involved in the photomorphogenesis and early development of Saccharina japonica porophytes (kelp). However the factors that interact with the SjAUREO under BL conditions specifically are not clear. Here in our study, three high quality cDNA libraries with CFU over 5 × 106 and a recombination rate of 100% were constructed respectively through white light (WL), BL and darkness (DK) treatments to the juvenile sporophytes. Based on the constructed cDNA libraries, the interactors of SjAUREO were screened and analyzed. There are eighty-four genes encoding the sixteen predicted proteins from the BL cDNA library, sixty-eight genes encoding eighteen predicted proteins from the DK cDNA library, and seventy-four genes encoding nineteen proteins from the WL cDNA library. All the predicted proteins are presumed to interact with SjAUREO when co-expressed with SjAUREO seperately. The 40S ribosomal protein S6 (RPS6), which only exists in the BL treated cDNA library except for two other libraries, and which is essential for cell proliferation and is involved in cell cycle progression, was selected for detailed analysis. We showed that its transcription was up-regulated by BL, and was highly transcribed in the basal blade (meristem region) of juvenile sporophytes but less in the distal part. Taken together, our results indicated that RPS6 was highly involved in BL-mediated kelp cellular division and photomorphogenesis by interacting with SjAUREO.
Control of Distributed Generators and Direct Harmonic Voltage Controlled Active Power Filters for Accurate Current Sharing and Power Quality Improvement in Islanded Microgrids
Authors: Munir Hafiz Mudassir , Ghannam Rami , Li Hong , Younas Talha , Golilarz Noorbakhsh Amiri , Hassan Mannan , Siddique Abubakar
Published: May 2019

Harmonics are regarded as one of the main challenges in a microgrid. This issue may even get worse when different distributed generators (DGs) work together to solve the load sharing problems due to mismatched feeder impedances and diversified DG ratings. Even though load sharing can be achieved, the microgrid suffers from voltage unbalance and total harmonic distortion (THD) issues at the output of DG terminals as well as at the point of common coupling (PCC). Thus, in this paper, the power quality improving method is discussed, with a target of load sharing under the hierarchical control of different DG units and an active power filter (APF) in microgrids. To achieve this objective, we propose integrating a direct harmonic voltage controlled APF with DGs to improve their harmonic compensation performance. This proposed control scheme has many advantages over conventional control using a shunt resistive active power filter (R-APF) with voltage controlled DGs. First, based on the existing THD level of the PCC voltage, the proposed scheme provides improved voltage compensation and reduction in THD in the islanded microgrid. Secondly, equal load sharing can be achieved simultaneously. Thus, the proposed scheme provides better performance and a seamless interface as the proposed study mainly contains both the voltage controlled DGs and the local based voltage detection APF.
Thermodynamics of Manufacturing Processes—The Workpiece and the Machinery
Authors: Osara Jude A.
Published: May 2019

Considered the world’s largest industry, manufacturing transforms billions of raw materials into useful products. Like all real processes and systems, manufacturing processes and equipment are subject to the first and second laws of thermodynamics and can be modeled via thermodynamic formulations. This article presents a simple thermodynamic model of a manufacturing sub-process or task, assuming multiple tasks make up the entire process. For example, to manufacture a machined component such as an aluminum gear, tasks include cutting the original shaft into gear blanks of desired dimensions, machining the gear teeth, surfacing, etc. The formulations presented here, assessing the workpiece and the machinery via entropy generation, apply to hand-crafting. However, consistent isolation and measurement of human energy changes due to food intake and work output alone pose a significant challenge; hence, this discussion focuses on standardized product-forming processes typically via machine fabrication.
Energy Yield Assessment from Ocean Currents in the Insular Shelf of Cozumel Island
Authors: Alcérreca-Huerta Juan Carlos , Encarnacion Job Immanuel , Ordoñez-Sánchez Stephanie , Callejas-Jiménez Mariana , Gallegos Diez Barroso Gabriel , Allmark Matthew , Mariño-Tapia Ismael , Silva Casarín Rodolfo , O’Doherty Tim , Johnstone Cameron , Carrillo Laura
Published: May 2019

Marine renewables represent a promising and innovative alternative source for satisfying the energy demands of growing populations while reducing the consumption of fossil fuels. Most technological advancements and energy yield assessments have focused on promoting the use of kinetic energy from tidal streams with flow velocities higher than 2.0 m s−1. However, slower-moving flows from ocean currents are recently explored due to their nearly continuous and unidirectional seasonal flows. In this study, the potential of the Yucatan Current was analysed at nearshore sites over the insular shelf of Cozumel Island in the Mexican Caribbean. Field measurements were undertaken using a vessel-mounted Acoustic Doppler Current Profiler (ADCP) to analyse the spatial distribution of flow velocities, along with Conductivity-temperature-depth (CTD) profiles as well as data gathering of bathymetry and water elevations. Northward directed flow velocities were identified, with increasing velocities just before the end of the strait of the Cozumel Channel, where average velocities in the region of 0.88–1.04 m s−1 were recorded. An estimation of power delivery using horizontal axis turbines was undertaken with Blade Element Momentum theory. It was estimated that nearly 3.2 MW could be supplied to Cozumel Island, amounting to about 10% of its electricity consumption.
Modeling Dislocation Contrasts Obtained by Accurate-Electron Channeling Contrast Imaging for Characterizing Deformation Mechanisms in Bulk Materials
Authors: KRIAA Hana , GUITTON Antoine , MALOUFI Nabila
Published: May 2019

Electron Channeling Contrast Imaging (ECCI) is becoming a powerful tool in materials science for characterizing deformation defects. Dislocations observed by ECCI in scanning electron microscope exhibit several features depending on the crystal orientation relative to the incident beam (white/black line on a dark/bright background). In order to bring new insights concerning these contrasts, we report an original theoretical approach based on the dynamical diffraction theory. Our calculations led, for the first time, to an explicit formulation of the back-scattered intensity as a function of various physical and practical parameters governing the experiment. Intensity profiles are modeled for dislocations parallel to the sample surface for different channeling conditions. All theoretical predictions are consistent with experimental results.
Evaluation of Friction and Wear Behavior of Date Palm Fruit Syrup as an Environmentally Friendly Lubricant
Authors: Tahir Mazin , Mohammed Abdul Samad , Muhammad Umar Azam
Published: May 2019

The effect of various operational factors, such as sliding speed, normal load and temperature on the tribological properties of Date palm fruit syrup (DPFS) as an environmentally friendly lubricant, is investigated. Ball-on-disc wear tests are conducted on mild steel samples in the presence of DPFS as a lubricant under different conditions and the coefficient of friction and wear rate are measured. Scanning electron microscopy, stylus profilometry, and Fourier transform infrared spectroscopy are used to evaluate the wear tracks to determine the underlying wear mechanisms. Results showed that DPFS has excellent tribological properties in terms of low friction and low wear rates making it a potential candidate to be used as a lubricant in tribological applications.
Lotus-Inspired Multiscale Superhydrophobic AA5083 Resisting Surface Contamination and Marine Corrosion Attack
Authors: Zhang Binbin , Xu Weichen , Zhu Qingjun , Yuan Shuai , Li Yantao
Published: May 2019

The massive and long-term service of 5083 aluminum alloy (AA5083) is restricted by several shortcomings in marine and industrial environments, such as proneness to localized corrosion attack, surface contamination, etc. Herein, we report a facile and cost-effective strategy to transform intrinsic hydrophilicity into water-repellent superhydrophobicity, combining fluorine-free chemisorption of a hydrophobic agent with etching texture. Dual-scale hierarchical structure, surface height relief and surface chemical elements were studied by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS), successively. Detailed investigations of the wetting property, self-cleaning effect, NaCl-particle self-propelling, corrosion and long-term behavior of the consequent superhydrophobic AA5083 surface were carried out, demonstrating extremely low adhesivity and outstanding water-repellent, self-cleaning and corrosion-resisting performance with long-term stability. We believe that the low cost, scalable and fluorine-free transforming of metallic surface wettability into waterproof superhydrophobicity is a possible strategy towards anti-contamination and marine anti-corrosion.
Novel Bioactive Penicipyrroether A and Pyrrospirone J from the Marine-Derived Penicillium sp. ZZ380
Authors: Song Tengfei , Tang Mingmin , Ge Hengju , Chen Mengxuan , Lian Xiaoyuan , Zhang Zhizhen
Published: May 2019

The marine-sourced fungus Penicillium sp. ZZ380 was previously reported to have the ability to produce a series of new pyrrospirone alkaloids. Further investigation on this strain resulted in the isolation and identification of novel penicipyrroether A and pyrrospirone J. Each of them represents the first example of its structural type, with a unique 6/5/6/5 polycyclic fusion that is different from the 6/5/6/6 fused ring system for the reported pyrrospirones. Their structures were elucidated by extensive nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) spectroscopic analyses, electronic circular dichroism (ECD) and 13C NMR calculations and X-ray single crystal diffraction. Penicipyrroether A showed potent antiproliferative activity against human glioma U87MG and U251 cells with half maximal inhibitory concentration (IC50) values of 1.64–5.50 μM and antibacterial inhibitory activity with minimum inhibitory concentration (MIC) values of 1.7 μg/mL against methicillin-resistant Staphylococcus aureus and 3.0 μg/mL against Escherichia coli.
Celiac-Related Autoantibodies and IL-17A in Bulgarian Patients with Dermatitis Herpetiformis: A Cross-Sectional Study
Authors: Velikova Tsvetelina , Shahid Martin , Ivanova-Todorova Ekaterina , Drenovska Kossara , Tumangelova-Yuzeir Kalina , Altankova Iskra , Vassileva Snejina
Published: May 2019

Background and objectives: Dermatitis herpetiformis (DH) is a blistering dermatosis, which shares common immunologic features with celiac disease (CD). The aim of the present study was to explore the performance of a panel of CD-related antibodies and IL-17A in Bulgarian patients with DH. Materials and Methods: Serum samples from 26 DH patients at mean age 53 ± 15 years and 20 healthy controls were assessed for anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin antibodies (AAA), and IL-17A by enzyme linked immuno-sorbent assay (ELISA), as well as anti-tTG, anti-gliadin (AGA), and anti-Saccharomyces cerevisiae antibodies (ASCA) using immunoblot. Results: The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and the cytokine IL-17A were at significantly higher levels in patients with DH compared to the average levels in healthy persons which stayed below the cut-off value (p < 0.05). Anti-DGP and anti-tTG antibodies showed the highest diagnostic sensitivity and specificity, as well as acceptable positive and negative predictive value. None of the healthy individuals was found positive for the tested antibodies, as well as for ASCA within the DH group. All tests showed good to excellent correlations (r = 0.5 ÷ 0.9, p < 0.01). Conclusions: Although the diagnosis of DH relies on skin biopsy for histology and DIF, serologic testing of a panel of celiac-related antibodies could be employed with advantages in the diagnosing process of DH patients. Furthermore, DH patients who are positive for the investigated serologic parameters could have routine monitoring for gastrointestinal complications typical for the gluten-sensitive enteropathy.
An Experimental and Simulated Study on Gas-Liquid Flow and Mixing Behavior in an ISASMELT Furnace
Authors: Zhao Hongliang , Lu Tingting , Yin Pan , Mu Liangzhao , Liu Fengqin
Published: May 2019

In this study, a water-model experiment and numerical simulation were carried out in a pilot ISASMELT furnace to study the factors affecting mixing time. The experimental results were compared to the simulation results to test the accuracy of the latter. To study the internal factors that affect the mixing time, the turbulent viscosity and flow field were calculated using simulation. In addition, following previous research, external factors that influence the mixing time including the depth of the submerged lance, lance diameter, gas flow rate, and the presence of a swirler were studied to investigate their effect on the flow regime. The results indicated that the mixing time is controlled by the turbulent viscosity and velocity vector. In addition, it was found that the lance diameter should not exceed 3.55 cm to maintain sufficient energy for stirring the bath. Finally, the optimal gas flow rate that offers the best mixing efficiency was found to be 50 Nm3/h.
Temporal Effects on Radiation Responses in Nonhuman Primates: Identification of Biofluid Small Molecule Signatures by Gas Chromatography–Mass Spectrometry Metabolomics
Authors: Pannkuk Evan , Laiakis Evagelia , Girgis Michael , Dowd Sarah , Dhungana Suraj , Nishita Denise , Bujold Kim , Bakke James , Gahagen Janet , Authier Simon , Chang Polly , Fornace, Jr. Albert
Published: May 2019

Whole body exposure to ionizing radiation damages tissues leading to physical symptoms which contribute to acute radiation syndrome. Radiation biodosimetry aims to determine characteristic early biomarkers indicative of radiation exposure and is necessary for effective triage after an unanticipated radiological incident. Radiation metabolomics can address this aim by assessing metabolic perturbations following exposure. Gas chromatography–mass spectrometry (GC-MS) is a standardized platform ideal for compound identification. We performed GC time-of-flight MS for the global profiling of nonhuman primate urine and serum samples up to 60 d after a single 4 Gy γ-ray total body exposure. Multivariate statistical analysis showed higher group separation in urine vs. serum. We identified biofluid markers involved in amino acid, lipid, purine, and serotonin metabolism, some of which may indicate host microbiome dysbiosis. Sex differences were observed for amino acid fold changes in serum samples. Additionally, we explored mitochondrial dysfunction by tricarboxylic acid intermediate analysis in the first week with a GC tandem quadrupole MS platform. By adding this temporal component to our previous work exploring dose effects at 7 d, we observed the highest fold changes occurring at 3 d, returning closer to basal levels by 7 d. These results emphasize the utility of both MS-based metabolomics for biodosimetry and complementary analytical platforms for increased metabolome coverage.
Anti-Inflammatory Compounds from Atractylodes macrocephala
Authors: Jeong Dawoon , Dong Guang-zhi , Lee Hwa Jin , Ryu Jae-Ha
Published: May 2019

In relation to anti-inflammatory agents from medicinal plants, we have isolated three compounds from Atractylodes macrocephala; 1, 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2, 5-cyclohexadiene-1, 4-dione; 2, 1-acetoxy-tetradeca-6E,12E-diene-8, 10-diyne-3-ol; 3, 1,3-diacetoxy-tetradeca-6E, 12E-diene-8, 10-diyne. Compounds 1–3 showed concentration-dependent inhibitory effects on production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that compounds 1–3 suppressed the protein and mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, compounds 1–3 inhibited transcriptional activity of nuclear factor-κB (NF-κB) and nuclear translocation of NF-κB in LPS-activated RAW 264.7 cells. The most active compound among them, compound 1, could reduce the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and suppress the phosphorylation of MAPK including p38, JNK, and ERK1/2. Taken together, these results suggest that compounds 1–3 from A. macrocephala can be therapeutic candidates to treat inflammatory diseases.
The Association between Green and Black Tea Consumption on Successful Aging: A Combined Analysis of the ATTICA and MEDiterranean ISlands (MEDIS) Epidemiological Studies
Authors: Naumovski Nenad , Foscolou Alexandra , D’Cunha Nathan M. , Tyrovolas Stefanos , Chrysohoou Christina , Sidossis Labros S. , Rallidis Loukianos , Matalas Antonia-Leda , Polychronopoulos Evangelos , Pitsavos Christos , Panagiotakos Demosthenes
Published: May 2019

Tea is one of the most-widely consumed beverages in the world with a number of different beneficial health effects, mainly ascribed to the polyphenolic content of the tea catechins. The aim of this study was to examine the consumption of green, black, or no tea, in relation to the previously validated successful ageing index (SAI; higher values “healthier” ageing) in a combined analysis of adults aged >50 years old from the ATTICA (n = 1128 adults from Athens, Greece metropolitan area) and the MEDiterranean Islands Study (MEDIS) (n = 2221 adults from various Greek island and Mani) studies. After adjusting for age, sex, smoking, and coffee consumption, green tea was positively associated with SAI (b ± SE: 0.225 ± 0.055, p < 0.001), while black tea was negatively associated with SAI (unstandardized b coefficient ± Standard error: −0.807 ± 0.054, p < 0.001). Green tea (vs black tea) consumption, had higher odds of a SAI of over 3.58 out of 10 (OR: 1.77, 95% CI: 1.38–2.28). Green tea consumption was also associated with higher levels of physical activity (p < 0.001) and reduced likelihood of hypertension (p = 0.006) compared with black tea. Two possible mechanisms are that green tea possesses high levels of catechins such as (−)-epigallocatechin 3-gallate and l-theanine compared with black tea. Therefore, the present analysis supports both the role of green tea constituents in successful ageing, as well as its role as an important component of an overall healthy diet in adults aged 50 years and over from these two epidemiological studies.
Synthesis and Cytotoxic Evaluation of 3-Methylidenechroman-4-ones
Authors: Kędzia Jacek , Bartosik Tomasz , Drogosz Joanna , Janecka Anna , Krajewska Urszula , Janecki Tomasz
Published: May 2019

In the search for new anticancer agents, a library of variously substituted 3-methylidenechroman-4-ones was synthesized using Horner–Wadsworth–Emmons methodology. Acylation of diethyl methylphosphonate with selected ethyl salicylates furnished 3-diethoxyphosphorylchromen-4-ones which were next used as Michael acceptors in the reaction with various Grignard reagents. The adducts were obtained as the mixtures of trans and cis diastereoisomers along with a small amount of enol forms. Their relative configuration and preferred conformation were established by NMR analysis. The adducts turned up to be effective Horner–Wadsworth–Emmons reagents giving 2-substituted 3-methylidenechroman-4-ones, which were then tested for their possible cytotoxic activity against two leukemia cell lines, HL-60 and NALM-6, and against MCF-7 breast cancer cell line. All new compounds (14a–o) were highly cytotoxic for the leukemic cells and showed a moderate or weak effect on MCF-7 cells. Analog 14d exhibited the highest growth inhibitory activity and was more potent than carboplatin against HL-60 (IC50 = 1.46 ± 0.16 µM) and NALM-6 (IC50 = 0.50 ± 0.05 µM) cells. Further tests showed that 14d induced apoptosis in NALM-6 cells, which was mediated mostly through the extrinsic pathway.
Assessment of Antidepressant Effect of the Aerial Parts of Micromeria myrtifolia Boiss. & Hohen on Mice
Authors: Küpeli Akkol Esra , Gürağaç Dereli Fatma Tuğçe , Ilhan Mert
Published: May 2019

The currently available antidepressant agents necessitate the development of newer alternatives because of their serious adverse effects and costs. Traditional medicinal knowledge is likely the key that opens the door to discover new medicines. In Turkish folk medicine, the infusion prepared from aerial parts of Micromeria myrtifolia Boiss. & Hohen is used as pleasure and medicinal tea for its relaxing action. The present research was conceived to confirm the antidepressant’s potential of this traditional medicinal plant. In this process, first of all, the collected and shade-dried aerial parts of M. myrtifolia were powdered and then, extracted using solvents with different polarity as follows; n-hexane, ethyl acetate (EtOAc), and methanol (MeOH). The antidepressant activity of the extracts was evaluated by using several in vivo and in vitro experimental models of depression. When the data obtained from the control and experimental groups were compared, it was determined that the MeOH extract was the most active. The active components of this extract were isolated and identified utilizing various chromatographic separation techniques. The MeOH extract was applied to reversed phase (RP-18) column chromatography to obtain five main fractions and they were tested on antidepressant activity models. The isolated compounds from the obtained fractions were elucidated as rosmarinic acid (1), myricetin (2), apigenin (3), and naringenin (4) which were assumed to be responsible for the antidepressant activity of the aerial parts. According to the results, rosmarinic acid, myricetin, apigenin, and naringenin showed statistically significant activity on forced swimming test and tetrabenazine-induced ptosis models, whereas only rosmarinic acid showed statistically significant activity on the tail suspension test. Apigenin displayed the highest inhibitory activity on MAO A and B enzymes. Studies in the future should be performed to investigate the antidepressant activity mechanism of these natural compounds. The current research could be an important step in the development of the new agents that can be used in the treatment of depression.
Zero-Bias Visible to Near-Infrared Horizontal p-n-p TiO2 Nanotubes Doped Monolayer Graphene Photodetector
Authors: Huang Zehua , Ji Chunhui , Cheng Luhua , Han Jiayue , Yang Ming , Wei Xiongbang , Jiang Yadong , Wang Jun
Published: May 2019

We present a p-n-p monolayer graphene photodetector doped with titanium dioxide nanotubes for detecting light from visible to near-infrared (405 to 1310 nm) region. The built-in electric field separates the photo-induced electrons and holes to generate photocurrent without bias voltage, which allows the device to have meager power consumption. Moreover, the detector is very sensitive to the illumination area, and we analyze the reason using the energy band theory. The response time of the detector is about 30 ms. The horizontal p-n-p device is a suitable candidate in zero-bias optoelectronic applications.
Solid-Phase Synthesis of Phosphorothioate/Phosphonothioate and Phosphoramidate/Phosphonamidate Oligonucleotides
Authors: Kostov Ondřej , Liboska Radek , Páv Ondřej , Novák Pavel , Rosenberg Ivan
Published: May 2019

We have developed a robust solid-phase protocol which allowed the synthesis of chimeric oligonucleotides modified with phosphodiester and O-methylphosphonate linkages as well as their P-S and P-N variants. The novel O-methylphosphonate-derived modifications were obtained by oxidation, sulfurization, and amidation of the O-methyl-(H)-phosphinate internucleotide linkage introduced into the oligonucleotide chain by H-phosphonate chemistry using nucleoside-O-methyl-(H)-phosphinates as monomers. The H-phosphonate coupling followed by oxidation after each cycle enabled us to successfully combine H-phosphonate and phosphoramidite chemistries to synthesize diversely modified oligonucleotide strands.
Synthesis, Docking and Biological Evaluation of a Novel Class of Imidazothiazoles as IDO1 Inhibitors
Authors: Serafini Marta , Torre Enza , Aprile Silvio , Massarotti Alberto , Fallarini Silvia , Pirali Tracey
Published: May 2019

IDO1, a key dioxygenase in tryptophan-kynurenine metabolism, appeared in the last 10 years at the vanguard of druggable targets in cancer therapy due to its well-established role both in immune escape and inflammatory neovascularization. Among the pool of IDO1 inhibitors that have entered clinical trials, none have reached approval. The identification of novel inhibitors endowed with better clinical profile, together with the further comprehension of the interactions with residues in IDO1 active site, are still a need. In this context, we have synthesized a novel class of imidazothiazole derivatives as IDO1 inhibitors and identified three compounds with inhibitory potency in the low micromolar range. This report strengthens the role played by pocket C in the active site of IDO1, providing novel directions in the design of IDO1 inhibitors.
New γ-Halo-δ-lactones and δ-Hydroxy-γ-lactones with Strong Cytotoxic Activity
Authors: Kamizela Angelika , Gawdzik Barbara , Urbaniak Mariusz , Lechowicz Łukasz , Białońska Agata , Kutniewska Sylwia Ewa , Gonciarz Weronika , Chmiela Magdalena
Published: May 2019

This paper presents the synthesis of γ -halo- δ -lactones, δ -iodo- γ -lactones and δ -hydroxy- γ -lactones from readily available organic substrates such as trans-crotonaldehyde and aryl bromides. Crystal structure analysis was carried out for lactones that were obtained in crystalline form. All halo- δ -lactones and δ -hydroxy- γ -lactones were highly cytotoxic against gastric cancer AGS cells with I C 50 values in the range of 0.0006–0.0044 mM. Some lactones showed high bactericidal activity against E. coli ATCC 8739 and S. aureus ATCC 65389, which reduced the number of CFU/mL by 70–83% and 87% respectively.
Improved Method for DNA Extraction and Purification from Tetrahymena pyriformis
Authors: El Maaiden Ezzouhra , El Kharrassi Youssef , Essamadi Abdel Khalid , Moustaid Khadija , Nasser Boubker
Published: May 2019

Tetrahymena pyriformis (protozoa) is intensely investigated as a model organism, offering numerous advantages in comprehensive and multidisciplinary studies using morphologic or molecular methods. Since DNA extraction is a vital step of any molecular experiment, here a new mixed surfactant (Sodium dodecyl sulfate (SDS) 20%/Triton X-100) was adopted for effective DNA extraction from Tetrahymena pyriformis under an easy, fast protocol. The efficiency of this technique was then compared with three widely-used alternative techniques, namely the Chelex 100 matrix, Ammonium pyrrolidine dithiocarbamate (APD) complex and SDS–chloroform methods. DNA extraction was analyzed by pulsed-field gel electrophoresis, spectral measurement, fluorometry (Qubit), restriction enzyme digestion, and polymerase chain reaction. Data analysis revealed that the quantity and quality of the recovered DNA varied depending on the applied DNA extraction method. The new method (SDS 20%/Triton X-100) was the most efficient for extracting DNA from Tetrahymena pyriformis with high integrity and purity, affordable cost, less time, and suitability for molecular applications.
Cyclodextrin–Amphiphilic Copolymer Supramolecular Assemblies for the Ocular Delivery of Natamycin
Authors: Lorenzo-Veiga Blanca , Sigurdsson Hakon Hrafn , Loftsson Thorsteinn , Alvarez-Lorenzo Carmen
Published: May 2019

Natamycin is the only drug approved for fungal keratitis treatment, but its low water solubility and low ocular penetration limit its efficacy. The purpose of this study was to overcome these limitations by encapsulating the drug in single or mixed micelles and poly(pseudo)rotaxanes. Soluplus and Pluronic P103 dispersions were prepared in 0.9% NaCl and pH 6.4 buffer, with or without α-cyclodextrin (αCD; 10% w/v), and characterized through particle size, zeta potential, solubilization efficiency, rheological properties, ocular tolerance, in vitro drug diffusion, and ex vivo permeation studies. Soluplus micelles (90–103 nm) and mixed micelles (150–110 nm) were larger than Pluronic P103 ones (16–20 nm), but all showed zeta potentials close to zero. Soluplus, Pluronic P103, and their mixed micelles increased natamycin solubility up to 6.00-fold, 3.27-fold, and 2.77-fold, respectively. Soluplus dispersions and poly(pseudo)rotaxanes exhibited in situ gelling capability, and they transformed into weak gels above 30 °C. All the formulations were non-irritant according to Hen’s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay. Poly(pseudo)rotaxanes facilitated drug accumulation into the cornea and sclera, but led to lower natamycin permeability through the sclera than the corresponding micelles. Poly(pseudo)rotaxanes made from mixed micelles showed intermediate natamycin diffusion coefficients and permeability values between those of Pluronic P103-based and Soluplus-based poly(pseudo)rotaxanes. Therefore, the preparation of mixed micelles may be a useful tool to regulate drug release and enhance ocular permeability.
Improving the Thermal and Mechanical Properties of Poly(l-lactide) by Forming Nanocomposites with an in Situ Ring-Opening Intermediate of Poly(l-lactide) and Polyhedral Oligomeric Silsesquioxane
Authors: Lei Xiu-Xiu , Lu Hao , Lu Lei , Xu Hai-Qing , Zhou Ying-Guo , Zou Jun
Published: May 2019

In this study, a series of poly(l-lactide) and (3-amino)-propylheptaisobutyl cage silsesquioxane (PLLA-AMPOSS) intermediates were first fabricated using single-arm in situ solution polymerization of LLA monomers and AMPOSS nanoparticles with different contents, 0.02–1.00 mol%. Then, the PLLA-AMPOSS intermediate with 0.5 mol% AMPOSS was selected as a representative and investigated by nuclear magnetic resonance (NMR) and X-ray diffraction (XRD). Afterwards, it was added into the pure PLLA with different mass fractions. Finally, the thermal behavior, crystallization kinetics, morphological characteristics, and mechanical properties of the obtained PLLA/PLLA-AMPOSS nanocomposites were carefully measured and investigated by differential scanning calorimetry (DSC), polarizing microscopy (POM), scanning electron microscopy (SEM), and tensile test. After comparing the PLLA-AMPOSS intermediate and PLLA/AMPOSS blend, the results show that the ring-open polymerization of PLLA-AMPOSS intermediate was successful. The results also show that the existence of PLLA-AMPOSS has a strong influence on the crystallization behavior of PLLA/PLLA-AMPOSS composites, which can be attributed to the heterogeneous nucleation effect of PLLA-AMPOSS. In addition, it was also found from the tensile test results that the addition of the PLLA-AMPOSS nanofiller improved the tensile strength and strain at break of PLLA/PLLA-AMPOSS nanocomposites. All of these results indicate the good nucleating effect of PLLA-AMPOSS and that the AMPOSS disperses well in the PLLA/PLLA-AMPOSS nanocomposites. A conclusion can be drawn that the selective nucleating agent and the combined method of in situ ring-opening polymerization and physical blending are feasible and effective.
The Role of Preventive Nutrition in Chronic Non-Communicable Diseases
Authors: Di Daniele Nicola
Published: May 2019

Over the last century, there has been a substantial change in the lifestyle and dietary habits of people worldwide [...]
Microneedle-Assisted Transdermal Delivery of Etanercept for Rheumatoid Arthritis Treatment
Authors: Cao Jian , Zhang Nan , Wang Ziyi , Su Jingjing , Yang Jing , Han Jiabing , Zhao Yongxing
Published: May 2019

Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.
Something’s Got to Give: Reconsidering the Justification for a Gender Divide in Sport
Authors: Bianchi Andria
Published: May 2019

The question of whether transgender athletes should be permitted to compete in accordance with their gender identity is an evolving debate. Most competitive sports have male and female categories. One of the primary challenges with this categorization system, however, is that some transgender athletes (and especially transgender women) may be prevented from competing in accordance with their gender identity. The reason for this restriction is because of the idea that transgender women have an unfair advantage over their cisgender counterparts; this is seen as a problem since sports are typically guided a principle called ‘the skill thesis’, which suggests that sports are supposed to determine who is most skillful by maintaining a fair starting point. In this paper, I argue that if the skill thesis ought to be maintained and there continues to exist no conclusive evidence in support of unfair advantages possessed by trans women, then we may want to re-consider the gender binary in sport. Rather than having male/female categories, it may make more sense to categorize athletes based other sport-specific factors (e.g., height, weight, etc.). This may help to maintain the skill thesis while at the same time removing potentially unfair and discriminatory barriers against transgender athletes.