bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Numerical Method for Pressure Loss Investigation in an Oil/Air Separator with Metal Foam in an Aero-Engine
Authors: Zhang Lifen , Zhang Xiaoxue , Liu Zhenxia
Published: January 2020

An efficient method of simulating pressure loss in a separator with metal foam is reported. In this method, a metal foam is modeled as a porous media having homogenized permeability and inertial resistance coefficients. The permeability and inertial resistance coefficients were obtained by a numerical method that was validated by experimental data from a literature. Then the pressure drop in the separator with metal foam replaced by porous media was efficiently simulated under different working conditions, and the results were analyzed. It was found that the porous media had a great effect on the pressure drop in the separator. As pores per inch (PPI) and rotating speed increase and porosity decreases, the pressure drop of the separator increases. The results indicate that replacing metal foam by porous media is effective and simulating the pressure drop is feasible and effective in a separator with metal foam.
Optimization of Electric Vehicle Charging Scheduling in Urban Village Networks Considering Energy Arbitrage and Distribution Cost
Authors: Srithapon Chitchai , Ghosh Prasanta , Siritaratiwat Apirat , Chatthaworn Rongrit
Published: January 2020

Electric vehicles (EV) replacing the internal combustion engine vehicle may be the solution for the particulate matter (PM) 2.5 pollution issue. However, the uncontrolled charging of EVs would challenge the power system operation. Therefore, it is necessary to implement some level of control over the EV charging procedure, especially in the residential network. In this paper, an optimization of EVs charging scheduling considering energy arbitrage and the distribution network cost of an urban village environment is presented. The optimized strategy focuses on decreasing the loss of EV owners’ energy arbitrage benefit, introduced as the penalty cost. Also, peak demand, power loss, and transformer aging are included in the estimation of the cost function for the distribution network. The optimization problem is solved using the genetic algorithm. As a case study, data from the urban village in Udon Thani, Thailand, are utilized to demonstrate the applicability of the proposed method. Simulation results show a reduction in the loss of energy arbitrage benefit, transformer peak load, power loss and the transformer loss of life. Therefore, the application of the optimized EV charging can prolong transformer lifetime benefiting both the EV owner and the distribution system operator.
Density, Viscosity and Free Energy of Activation for Viscous Flow of Monoethanol Amine (1) + H2O (2) + CO2 (3) Mixtures
Authors: Karunarathne Sumudu S. , Eimer Dag A. , Øi Lars E.
Published: January 2020

Densities and viscosities of aqueous monoethanol amine (MEA) and CO2-loaded aqueous MEA are highly relevant in engineering calculations to perform process design and simulations. Density and viscosity of the aqueous MEA were measured in the temperature range of 293.15 K to 363.15 K with MEA mass fractions ranging from 0.3 to 1.0. Densities of the aqueous MEA were fitted for a density correlation. Eyring’s viscosity model based on absolute rate theory was adopted to determine the excess free energy of activation for viscous flow of aqueous MEA mixtures and was correlated by a Redlich–Kister polynomial. Densities and viscosities of CO2-loaded MEA solutions were measured in the temperature range of 293.15 K to 353.15 K with MEA mass fractions of 0.3, 0.4 and 0.5. The density correlation used to correlate aqueous MEA was modified to fit CO2-loaded density data. The free energy of activation for viscous flow for CO2-loaded aqueous MEA solutions was determined by Eyring’s viscosity model and a correlation was proposed to represent free energy of activation for viscous flow and viscosity. This can be used to evaluate quantitative and qualitative properties in the MEA + H2O + CO2 mixture.
The High Content of Ent-11α-hydroxy-15-oxo-kaur- 16-en-19-oic Acid in Adenostemma lavenia (L.) O. Kuntze Leaf Extract: With Preliminary in Vivo Assays
Authors: Hamamoto Akie , Isogai Ryosuke , Maeda Miwa , Hayazaki Masumi , Horiyama Eito , Takashima Shigeo , Koketsu Mamoru , Takemori Hiroshi
Published: January 2020

Background: Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA) is a multifunctional biochemical found in some ferns, Pteris semipinnata, and its congeneric species. Although a number of therapeutic applications of 11αOH-KA have been proposed (e.g., anti-cancer, anti-inflammation, and skin whitening), the content of 11αOH-KA in these ferns is not high. Adenostemma lavenia (L.) O. Kuntze, an Asteraceae, has also been reported to contain 11αOH-KA. The decoction (hot water extract) of whole plants of A. lavenia is used as a folk remedy for inflammatory disorders, such as hepatitis and pneumonia, suggesting that 11αOH-KA may be the ingredient responsible for the medicinal properties of this plant. Methods: The anti-melanogenic activities of the water extracts of A. lavenia leaves and Pteris dispar Kunze (a cognate of P. semipinnata) leaves were compared in mouse B16F10 melanoma cells. The amount of 11αOH-KA was measured by using liquid chromatography spectrometry. C57BL/6J mice were treated with the water extract of A. lavenia leaf, and the blood concentration of 11αOH-KA was measured. The in vivo efficacy of the water extract of A. lavenia leaf was evaluated according to tis anti-melanogenic activity by monitoring hair color. Results: Although both the extracts (A. lavenia and P. dispar Kunze) showed high anti-melanogenic activities, only A. lavenia contained a high amount of 11αOH-KA, approximately 2.5% of the dry leaf weight. 11αOH-KA can be purified from A. lavenia leaves in two steps: water extraction followed by chloroform distribution. The treatment of mice with the water extract of A. lavenia leaf suppresses pigmentation in their hairs. Conclusions: Despite the small number of mice examined, the present preliminary result of the suppressed hair pigmentation suggests that the water extract of A. lavenia leaf and the ingredient that is possibly responsible for this—11αOH-KA—are new materials for oral cosmetics. The results may also be helpful in the future development of functional foods and methods to treat patients suffering from hyperpigmentation disorders, such as melasma.
Aromatic Characterization of Mangoes (Mangifera indica L.) Using Solid Phase Extraction Coupled with Gas Chromatography–Mass Spectrometry and Olfactometry and Sensory Analyses
Authors: Liu Haocheng , An Kejing , Su Siqi , Yu Yuanshan , Wu Jijun , Xiao Gengsheng , Xu Yujuan
Published: January 2020

Mangoes (Mangifera indica L.) are wildly cultivated in China with different commercial varieties; however, characterization of their aromatic profiles is limited. To better understand the aromatic compounds in different mango fruits, the characteristic aromatic components of five Chinese mango varieties were investigated using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry-gas chromatography-olfactometry (GC-MS-O) techniques. Five major types of substances, including alcohols, terpenes, esters, aldehydes, and ketones were detected. GC-O (frequency detection (FD)/order-specific magnitude estimation (OSME)) analysis identified 23, 20, 20, 24, and 24 kinds of aromatic components in Jinmang, Qingmang, Guifei, Hongyu, and Tainong, respectively. Moreover, 11, 9, 9, 8, and 17 substances with odor activity values (OAVs) ≥1 were observed in Jinmang, Qingmang, Guifei, Hongyu, and Tainong, respectively. Further sensory analysis revealed that the OAV and GC-O (FD/OSME) methods were coincided with the main sensory aromatic profiles (fruit, sweet, flower, and rosin aromas) of the five mango pulps. Approximately 29 (FD ≥ 6, OSME ≥ 2, OAV ≥ 1) aroma-active compounds were identified in the pulps of five mango varieties, namely, γ-terpinene, 1-hexanol, hexanal, terpinolene trans-2-heptenal, and p-cymene, which were responsible for their special flavor. Aldehydes and terpenes play a vital role in the special flavor of mango, and those in Tainong were significantly higher than in the other four varieties.
Modulation of Placental Gene Expression in Small-for-Gestational-Age Infants
Authors: O’Callaghan Jessica L. , Clifton Vicki L. , Prentis Peter , Ewing Adam , Miller Yvette D. , Pelzer Elise S.
Published: January 2020

Small-for-gestational-age (SGA) infants are fetuses that have not reached their genetically programmed growth potential. Low birth weight predisposes these infants to an increased risk of developing cardiovascular, metabolic and neurodevelopmental conditions in later life. However, our understanding of how this pathology occurs is currently incomplete. Previous research has focused on understanding the transcriptome, epigenome and bacterial signatures separately. However, we hypothesise that interactions between moderators of gene expression are critical to understanding fetal growth restriction. Through a review of the current literature, we identify that there is evidence of modulated expression/methylation of the placental genome and the presence of bacterial DNA in the placental tissue of SGA infants. We also identify that despite limited evidence of the interactions between the above results, there are promising suggestions of a relationship between bacterial signatures and placental function. This review aims to summarise the current literature concerning fetal growth from multiple avenues and propose a novel relationship between the placental transcriptome, methylome and bacterial signature that, if characterised, may be able to improve our current understanding of the placental response to stress and the aetiology of growth restriction.
A Gravity-Based Food Flow Model to Identify the Source of Foodborne Disease Outbreaks
Authors: Schlaich Tim , Horn Abigail L. , Fuhrmann Marcel , Friedrich Hanno
Published: January 2020

Computational traceback methodologies are important tools for investigations of widespread foodborne disease outbreaks as they assist investigators to determine the causative outbreak location and food item. In modeling the entire food supply chain from farm to fork, however, these methodologies have paid little attention to consumer behavior and mobility, instead making the simplifying assumption that consumers shop in the area adjacent to their home location. This paper aims to fill this gap by introducing a gravity-based approach to model food-flows from supermarkets to consumers and demonstrating how models of consumer shopping behavior can be used to improve computational methodologies to infer the source of an outbreak of foodborne disease. To demonstrate our approach, we develop and calibrate a gravity model of German retail shopping behavior at the postal-code level. Modeling results show that on average about 70 percent of all groceries are sourced from non-home zip codes. The value of considering shopping behavior in computational approaches for inferring the source of an outbreak is illustrated through an application example to identify a retail brand source of an outbreak. We demonstrate a significant increase in the accuracy of a network-theoretic source estimator for the outbreak source when the gravity model is included in the food supply network compared with the baseline case when contaminated individuals are assumed to shop only in their home location. Our approach illustrates how gravity models can enrich computational inference models for identifying the source (retail brand, food item, location) of an outbreak of foodborne disease. More broadly, results show how gravity models can contribute to computational approaches to model consumer shopping interactions relating to retail food environments, nutrition, and public health.
The Inorganic Component as a Possible Marker for Quality and for Authentication of the Hazelnut’s Origin
Authors: Inaudi Paolo , Giacomino Agnese , Malandrino Mery , La Gioia Carmela , Conca Eleonora , Karak Tanmoy , Abollino Ornella
Published: January 2020

The inorganic component of hazelnuts was considered as a possible marker for geographical allocation and for the assessment of technological impact on their quality. The analyzed samples were Italian hazelnuts of the cultivar Tonda Gentile Romana and Turkish hazelnuts of the cultivars Tombul, Palaz and Çakildak. The hazelnuts were subjected to different drying procedures and different conservative methods. The concentration of 13 elements, namely Ba, Ca, Cu, Fe, K, Mg, Mn, Na, Ni, P, Sn, Sr and Zn, were quantified by inductively coupled plasma optical emission spectroscopy (ICP-OES). All the samples were previously digested in a microwave oven. Before proceeding with the analysis of the samples, the whole procedure was optimized and tested on a certified reference material. The results show that the inorganic component: (i) can represent a fingerprint, able to identify the geographical origin of hazelnuts, becoming an important quality marker for consumer protection; (ii) is strongly influenced by the treatments undergone by the investigated product during all the processing stages. A pilot study was also carried out on hazelnuts of the cultivar Tonda Gentile Trilobata Piemontese, directly harvested from the plant during early development to maturity and analyzed to monitor the element concentration over time.
“It’s Just Addictive People That Make Addictive Videos”: Children’s Understanding of and Attitudes towards Influencer Marketing of Food and Beverages by YouTube Video Bloggers
Authors: Coates Anna Elizabeth , Hardman Charlotte Alice , Halford Jason Christian Grovenor , Christiansen Paul , Boyland Emma Jane
Published: January 2020

Exposure to influencer marketing of foods and beverages high in fat, sugar, and/or salt (HFSS) increases children’s immediate intake. This study qualitatively explored children’s understanding of, and attitudes towards, this marketing, to elucidate potential mechanisms through which exposure affects behavior. In six focus groups (n = 4) children (10–11 years) were shown a YouTube video featuring influencer marketing of an HFSS product. Inductive thematic analysis identified six themes from children’s discussions of this marketing: (1) YouTubers fill a gap in children’s lives, (2) the accessibility of YouTubers increases children’s understanding of their actions, (3) influencer marketing impacts all—the influencer, the brand, and the viewer, (4) attitudes towards influencer marketing are most affected by a YouTuber’s familiarity, (5) YouTuber influencer marketing is effective because they are not ‘strangers’, (6) children feel able to resist influencer marketing of HFSS products. Children had an understanding of the persuasive intent of this marketing, and although most were sceptical, familiar YouTubers elicited particularly sympathetic attitudes. Children felt affected by influencer marketing of HFSS products, but believed they were able to resist it. Beyond theoretical insight, this study adds to the growing body of evidence to suggest children’s exposure to HFSS influencer marketing should be reduced.
Perceptions of the English Use of College Transfer Nursing Students in a Non-English Speaking City: A Qualitative Study
Authors: Ching Shirley Siu Yin , Foung Dennis , Zhang Lillian Weiwei , Guan Gwendoline Yuanyuan , Cheung Kin
Published: January 2020

There has been limited research on nursing students’ (NSs) language problems conducted in non-English speaking countries, especially research focusing on college transfer students. The purpose of this study was to explore the perceived needs and challenges of English use by college transfer NSs in a non-English speaking environment. A descriptive study design was adopted. Forty-five college transfer NSs from a university in Hong Kong participated in the study. Sixteen interviews were conducted. A qualitative content analysis was performed. Two main categories were identified: (a) Perceptions about English use (three sub-categories: (i) significance of having a good command of English; (ii) challenges in use of English; and (iii) low motivation and need to learn English), and (b) using English in nursing contexts (two sub-categories: (i) challenges in the use of English in nursing and (ii) improving English proficiency as a second priority in nursing students). In conclusion, college transfer NSs face challenges in general and discipline-specific English use, but their motivation to improve their English proficiency was not strong. Language centers should re-design the language courses to meet NSs’ communication needs, while nursing educators should provide opportunities for students to strengthen their English use in research and clinical situations.
Open Campus Policies: How Built, Food, Social, and Organizational Environments Matter for Oregon’s Public High School Students’ Health
Authors: Budd Elizabeth L. , Liévanos Raoul S. , Amidon Brigette
Published: January 2020

Open campus policies that grant access to the off-campus food environment may influence U.S. high school students’ exposure to unhealthy foods, yet predictors of these policies are unknown. Policy holding and built (walkability), food (access to grocery stores), social (school-to-neighborhood demographic similarity), and organizational (policy holding of neighboring schools) environment data were collected for 200 Oregon public high schools. These existing data were derived from the Oregon School Board Association, WalkScore.com, the 2010 Decennial Census, the 2010–2014 American Community Survey, the Supplemental Nutrition Assistance Program, TDLinex, Nielson directories, the U.S. Department of Education, the National Center for Education Statistics, and the Common Core of Data. Most (67%) of Oregon public high schools have open campus policies. Logistic regression analyses modeled open campus policy holding as a function of built, food, social, and organizational environment influences. With health and policy implications, the results indicate that the schools’ walkability, food access, and extent of neighboring open campus policy-schools are significantly associated with open campus policy holding in Oregon.
BCL-xL, a Mitochondrial Protein Involved in Successful Aging: From C. elegans to Human Centenarians
Authors: Borrás Consuelo , Mas-Bargues Cristina , Román-Domínguez Aurora , Sanz-Ros Jorge , Gimeno-Mallench Lucia , Inglés Marta , Gambini Juan , Viña José
Published: January 2020

B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways can be both beneficial or detrimental depending on the circumstances. Thus, targeting BCL-xL would in turn be a “double-edge sword” and therefore, additional studies are needed to better comprehend this dual and apparently contradictory role of BCL-XL in longevity.
Maternal Recognition of Pregnancy in the Horse: Are MicroRNAs the Secret Messengers?
Authors: Smits Katrien , Gansemans Yannick , Tilleman Laurentijn , Van Nieuwerburgh Filip , Van De Velde Margot , Gerits Ilse , Ververs Cyrillus , Roels Kim , Govaere Jan , Peelman Luc , Deforce Dieter , Van Soom Ann
Published: January 2020

The signal for maternal recognition of pregnancy (MRP) has still not been identified in the horse. High-throughput molecular biology at the embryo–maternal interface has substantially contributed to the knowledge on pathways affected during MRP, but an integrated study in which proteomics, transcriptomics and miRNA expression can be linked directly is currently lacking. The aim of this study was to provide such analysis. Endometrial biopsies, uterine fluid, embryonic tissues, and yolk sac fluid were collected 13 days after ovulation during pregnant and control cycles from the same mares. Micro-RNA-Sequencing was performed on all collected samples, mRNA-Sequencing on the same tissue samples and mass spectrometry was conducted previously on the same fluid samples. Differential expression of miRNA, mRNA and proteins showed high conformity with literature and confirmed involvement in pregnancy establishment, embryo quality, steroid synthesis and prostaglandin regulation, but the link between differential miRNAs and their targets was limited and did not indicate the identity of an unequivocal signal for MRP in the horse. Differential expression at the embryo–maternal interface was prominent, highlighting a potential role of miRNAs in embryo–maternal communication during early pregnancy in the horse. These data provide a strong basis for future targeted studies.
Light Pollution Changes the Toxicological Effects of Cadmium on Microbial Community Structure and Function Associated with Leaf Litter Decomposition
Authors: Liu Zhuangzhuang , Lv Yanna , Ding Rongcai , Chen Xiaxia , Pu Gaozhong
Published: January 2020

Artificial light at night (ALAN/A) can not only alter the behavior and communication of biological organisms, it can also interact with other stressors. Despite its widespread use and the numerous potential ecological effects, little is known about the impact of ALAN on plant litter decomposition under cadmium (Cd) pollution in aquatic ecosystems. In an indoor microcosm experiment, we tested single and combined effects of ALAN and Cd on the activities and community structure of fungi associated with plant litter. The results showed that ALAN and/or Cd can change both water and leaf litter characteristics. ALAN exposure not only altered fungal community structure and their correlations, but also increased the activities of alkaline phosphatase, β-glucosidase, and cellobiohydrolase. The leaf litter decomposition rate was 71% higher in the A-Cd treatment than that in the N-Cd treatment, indicating that the presence of ALAN weakened the negative impact of Cd on leaf litter decomposition. These results suggested that ALAN exposure mitigated the negative effect of Cd on leaf litter decomposition, contributing to the duel effect of ALAN on leaf litter decomposition. Overall, the results expand our understanding of ALAN on the environment and highlight the contribution of ALAN to Cd toxicity in aquatic ecosystems.
Isolation of Four Lytic Phages Infecting Klebsiella pneumoniae K22 Clinical Isolates from Spain
Authors: Domingo-Calap Pilar , Beamud Beatriz , Vienne Justine , González-Candelas Fernando , Sanjuán Rafael
Published: January 2020

The emergence of multi-drug-resistant bacteria represents a major public-health threat. Phages constitute a promising alternative to chemical antibiotics due to their high host specificity, abundance in nature, and evolvability. However, phage host specificity means that highly diverse bacterial species are particularly difficult to target for phage therapy. This is the case of Klebsiella pneumoniae, which presents a hypervariable extracellular matrix capsule exhibiting dozens of variants. Here, we report four novel phages infecting K. pneumoniae capsular type K22 which were isolated from environmental samples in Valencia, Spain. Full genome sequencing showed that these phages belong to the Podoviridae family and encode putative depolymerases that allow digestion of specific K22 K. pneumoniae capsules. Our results confirm the capsular type-specificity of K. pneumoniae phages, as indicated by their narrow infectivity in a panel of K. pneumoniae clinical isolates. Nonetheless, this work represents a step forward in the characterization of phage diversity, which may culminate in the future use of large panels of phages for typing and/or for combating multi-drug-resistant K. pneumoniae.
Megavoltage Radiosensitization of Gold Nanoparticles on a Glioblastoma Cancer Cell Line Using a Clinical Platform
Authors: Kazmi Farasat , Vallis Katherine A. , Vellayappan Balamurugan A. , Bandla Aishwarya , Yukun Duan , Carlisle Robert
Published: January 2020

Gold nanoparticles (GNPs) have demonstrated significant dose enhancement with kilovoltage (kV) X-rays; however, recent studies have shown inconsistent findings with megavoltage (MV) X-rays. We propose to evaluate the radiosensitization effect on U87 glioblastoma (GBM) cells in the presence of 42 nm GNPs and irradiated with a clinical 6 MV photon beam. Cytotoxicity and radiosensitization were measured using MTS and clonogenic cellular radiation sensitivity assays, respectively. The sensitization enhancement ratio was calculated for 2 Gy (SER2Gy) with GNP (100 μg/mL). Dark field and MTS assays revealed high co-localization and good biocompatibility of the GNPs with GBM cells. A significant sensitization enhancement of 1.45 (p = 0.001) was observed with GNP 100 μg/mL. Similarly, at 6 Gy, there was significant difference in the survival fraction between the GBM alone group (mean (M) = 0.26, standard deviation (SD) = 0.008) and the GBM plus GNP group (M = 0.07, SD = 0.05, p = 0.03). GNPs enabled radiosensitization in U87 GBM cells at 2 Gy when irradiated using a clinical platform. In addition to the potential clinical utility of GNPs, these studies demonstrate the effectiveness of a robust and easy to standardize an in-vitro model that can be employed for future studies involving metal nanoparticle plus irradiation.
Fate Determination of ZnO in Commercial Foods and Human Intestinal Cells
Authors: Jeon Ye-Rin , Yu Jin , Choi Soo-Jin
Published: January 2020

(1) Background: Zinc oxide (ZnO) particles are widely used as zinc (Zn) fortifiers, because Zn is essential for various cellular functions. Nanotechnology developments may lead to production of nano-sized ZnO, although nanoparticles (NPs) are not intended to be used as food additives. Current regulations do not specify the size distribution of NPs. Moreover, ZnO is easily dissolved into Zn ions under acidic conditions. However, the fate of ZnO in commercial foods or during intestinal transit is still poorly understood. (2) Methods: We established surfactant-based cloud point extraction (CPE) for ZnO NP detection as intact particle forms using pristine ZnO-NP-spiked powdered or liquid foods. The fate determination and dissolution characterization of ZnO were carried out in commercial foods and human intestinal cells using in vitro intestinal transport and ex vivo small intestine absorption models. (3) Results: The results demonstrated that the CPE can effectively separate ZnO particles and Zn ions in food matrices and cells. The major fate of ZnO in powdered foods was in particle form, in contrast to its ionic fate in liquid beverages. The fate of ZnO was closely related to the extent of its dissolution in food or biomatrices. ZnO NPs were internalized into cells in both particle and ion form, but dissolved into ions with time, probably forming a Zn–ligand complex. ZnO was transported through intestinal barriers and absorbed in the small intestine primarily as Zn ions, but a small amount of ZnO was absorbed as particles. (4) Conclusion: The fate of ZnO is highly dependent on food matrix type, showing particle and ionic fates in powdered foods and liquid beverages, respectively. The major intracellular and intestinal absorption fates of ZnO NPs were Zn ions, but a small portion of ZnO particle fate was also observed after intestinal transit. These findings suggest that the toxicity of ZnO is mainly related to the Zn ion, but potential toxicity resulting from ZnO particles cannot be completely excluded.
Preferential Coupling of Dopamine D2S and D2L Receptor Isoforms with Gi1 and Gi2 Proteins—In Silico Study
Authors: Żuk Justyna , Bartuzi Damian , Matosiuk Dariusz , Kaczor Agnieszka A.
Published: January 2020

The dopamine D2 receptor belongs to rhodopsin-like G protein-coupled receptors (GPCRs) and it is an important molecular target for the treatment of many disorders, including schizophrenia and Parkinson’s disease. Here, computational methods were used to construct the full models of the dopamine D2 receptor short (D2S) and long (D2L) isoforms (differing with 29 amino acids insertion in the third intracellular loop, ICL3) and to study their coupling with Gi1 and Gi2 proteins. It was found that the D2L isoform preferentially couples with the Gi2 protein and D2S isoform with the Gi1 protein, which is in accordance with experimental data. Our findings give mechanistic insight into the interplay between isoforms of dopamine D2 receptors and Gi proteins subtypes, which is important to understand signaling by these receptors and their mediation by pharmaceuticals, in particular psychotic and antipsychotic agents.
Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway
Authors: Khan Abdul Q. , Ahmed Eiman I. , Elareer Noor , Fathima Hamna , Prabhu Kirti S. , Siveen Kodappully S. , Kulinski Michal , Azizi Fouad , Dermime Said , Ahmad Aamir , Steinhoff Martin , Uddin Shahab
Published: January 2020

The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705–STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study’s findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes.
Cell-Penetrating Peptides Enhance the Activity of Human Fibroblast Growth Factor 2 by Prolonging the Retention Time: A New Vision for Drug-Delivery Systems
Authors: Lee Jaehoon , Kwon Mijin , Oh Naeun , Park Jaehyun , Park Sangkyu , Seo Jeongmin , Roh Sangho
Published: January 2020

Cell-penetrating peptides (CPPs) are defined by their ability to deliver cargo into cells and have been studied and developed as a promising drug-delivery system (DDS). However, the issue of whether the CPPs that have already entered the cells can be re-released or reused has not been studied. The purpose of this research was to construct CPP-conjugated human fibroblast growth factor 2 (hFGF2) and investigate whether they can be re-released from the cell membrane for reuse. This study combined hFGF2 with Tat or Ara27, a newly developed CPP derived from the zinc knuckle (CCHC-type) family protein of Arabidopsis. Human dermal fibroblast (HDF) was treated with Tat-conjugated hFGF2 (tFGF2) and Ara27-conjugated hFGF2 (NR-FGF2) for both long and short durations, and the effects on cell growth were compared. Furthermore, tFGF2 and NR-FGF2 re-released from the cells were quantified and the effects were evaluated by culturing HDF in a conditioned medium. Interestingly, the proliferation of HDF increased only when NR-FGF2 was treated for 1 h in endocytosis-independent manner. After 1 h, NR-FGF2 was significantly re-released, reaching a maximum concentration at 5 h. Furthermore, increased proliferation of HDF cultured in the conditioned medium containing re-released NR-FGF2 was discovered. While previous studies have focused on the delivery of cargo and its associated applications, this study has revealed that combinations of superior CPPs and therapeutics can be expected to prolong both the retention time and the cell-penetrating capacity, even in the presence of external factors. Therefore, CPPs can be applied in the context of topical drugs and cosmetics as a new DDS approach.
Night Matters—Why the Interdisciplinary Field of “Night Studies” Is Needed
Authors: Kyba Christopher C.M. , Pritchard Sara B. , Ekirch A. Roger , Eldridge Adam , Jechow Andreas , Preiser Christine , Kunz Dieter , Henckel Dietrich , Hölker Franz , Barentine John , Berge Jørgen , Meier Josiane , Gwiazdzinski Luc , Spitschan Manuel , Milan Mirik , Bach Susanne , Schroer Sibylle , Straw Will
Published: January 2020

The night has historically been neglected in both disciplinary and interdisciplinary research. To some extent, this is not surprising, given the diurnal bias of human researchers and the difficulty of performing work at night. The night is, however, a critical element of biological, chemical, physical, and social systems on Earth. Moreover, research into social issues such as inequality, demographic changes, and the transition to a sustainable economy will be compromised if the night is not considered. Recent years, however, have seen a surge in research into the night. We argue that “night studies” is on the cusp of coming into its own as an interdisciplinary field, and that when it does, the field will consider questions that disciplinary researchers have not yet thought to ask.
Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover
Authors: Verster Joris C. , Kruisselbrink L. Darren , Slot Karin A. , Anogeianaki Aikaterini , Adams Sally , Alford Chris , Arnoldy Lizanne , Ayre Elisabeth , Balikji Stephanie , Benson Sarah , Bruce Gillian , Devenney Lydia E. , Frone Michael R. , Gunn Craig , Heffernan Thomas , Hensel Kai O. , Hogewoning Anna , Johnson Sean J. , van Lawick van Pabst Albertine E. , van de Loo Aurora J.A.E. , Mackus Marlou , Merlo Agnese , Murphy René J.L. , Owen Lauren , Palmer Emily O.C. , van Rossum Charmaine J.I. , Scholey Andrew , Terpstra Chantal , Vatsalya Vatsalya , Vermeulen Sterre A. , van Wijk Michelle , Stock Ann-Kathrin
Published: January 2020

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their “normal” drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their “regular” drinking level, considerably higher alcohol intake—irrespective of the absolute amount—may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.
Genome-Wide Association Study of Opioid Cessation
Authors: Cox Jiayi W. , Sherva Richard M. , Lunetta Kathryn L. , Johnson Emma C. , Martin Nicholas G. , Degenhardt Louisa , Agrawal Arpana , Nelson Elliot C. , Kranzler Henry R. , Gelernter Joel , Farrer Lindsay A.
Published: January 2020

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.
Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume
Authors: Conic Rosalynn RZ , Damiani Giovanni , Schrom Kory P. , Ramser Amy E. , Zheng Chunlei , Xu Rong , McCormick Thomas S. , Cooper Kevin D.
Published: January 2020

In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.
Molecular Detection of Aspergillus: Application of a Real-Time PCR Multiplex Assay in Tissue Samples
Authors: Sabino Raquel , Simões Helena , Veríssimo Cristina
Published: January 2020

Diagnosis of invasive fungal infections is complex, and the lack of standardization of molecular methods is still a challenge. Several methods are available for the diagnosis of invasive aspergillosis, but their effectiveness will depend on the studied population, the patients’ comorbidities, and the use of mold active prophylaxis, among others. The ability to determine the identity of the infecting Aspergillus species, and to detect mutations conferring specific resistance patterns directly from DNA extracted from the biological product, is an advantage of nucleic acid testing compared with antigen-based assays. In this study, we present laboratory cases where the diagnosis of aspergillosis was performed using a real-time multiplex PCR for the detection of Aspergillus DNA in tissue samples, showing its usefulness as one more tool in the diagnosis of aspergillosis in tissue samples. Aspergillus real-time multiplex PCR was also used to detect azole-resistance in some cases. In the majority of the PCR positive cases, cultures remained negative after 60 days. The PCR assay directed to Aspergillus gave positive signals for Aspergillus fumigatus sensu stricto. Results were confirmed by panfungal PCR, followed by sequencing, revealing 100% homology with Aspergillus fumigatus sensu stricto. Mutations conferring azole resistance were not detected.
Understanding Landscape Influences on Aquatic Fauna across the Central and Southern Appalachians
Authors: Hanks R. Daniel , Leonard Paul B. , Baldwin Robert F.
Published: January 2020

For the success of aquatic conservation efforts, it is imperative for there to be an understanding of the influences multiple stressors across the landscape have on aquatic biota, as it provides an understanding of spatial patterns and informs regional stakeholders. The central and southern Appalachians contain biodiversity hotspots for aquatic fauna. Therefore, we sought to create a comprehensive multimetric model that is based on the influence of abiotic factors on fish and aquatic macroinvertebrates that could predict watershed quality. Good spatial coverage exists for land use/land cover (LULC) and other physicochemical components throughout the region, yet biological data is unevenly distributed, which creates difficulties in making informed management and conservation decisions across large landscapes. We used boosted regression trees (BRT) to model a variety of biological responses (fish and aquatic macroinvertebrate variables) to abiotic predictors and by combining model outputs created a single score for both abiotic and biotic values throughout the region. The mean variance that was explained by BRT models for fish was 73% (range = 48–85%) and for aquatic macroinvertebrates was 81% (range = 76–89%). We categorized both predictor and response variables into themes and targets, respectively, to better understand large scale patterns on the landscape that influence biological condition of streams. The most important themes in our models were geomorphic condition for fish and water quality for aquatic macroinvertebrates. Regional models were developed for fish, but not for aquatic macroinvertebrates due to the low number of sample sites. There was strong correlation between regional and global watershed scores for fish models but not between fish and aquatic macroinvertebrate models. We propose that the use of such multimetric scores can inform managers, NGOs, and private land owners regarding land use practices, thereby contributing to large landscape scale conservation efforts.
Highly Sensitive Biosensors Based on Biomolecules and Functional Nanomaterials Depending on the Types of Nanomaterials: A Perspective Review
Authors: Yoon Jinho , Shin Minkyu , Lee Taek , Choi Jeong-Woo
Published: January 2020

Biosensors are very important for detecting target molecules with high accuracy, selectivity, and signal-to-noise ratio. Biosensors developed using biomolecules such as enzymes or nucleic acids which were used as the probes for detecting the target molecules were studied widely due to their advantages. For example, enzymes can react with certain molecules rapidly and selectively, and nucleic acids can bind to their complementary sequences delicately in nanoscale. In addition, biomolecules can be immobilized and conjugated with other materials by surface modification through the recombination or introduction of chemical linkers. However, these biosensors have some essential limitations because of instability and low signal strength derived from the detector biomolecules. Functional nanomaterials offer a solution to overcome these limitations of biomolecules by hybridization with or replacing the biomolecules. Functional nanomaterials can give advantages for developing biosensors including the increment of electrochemical signals, retention of activity of biomolecules for a long-term period, and extension of investigating tools by using its unique plasmonic and optical properties. Up to now, various nanomaterials were synthesized and reported, from widely used gold nanoparticles to novel nanomaterials that are either carbon-based or transition-metal dichalcogenide (TMD)-based. These nanomaterials were utilized either by themselves or by hybridization with other nanomaterials to develop highly sensitive biosensors. In this review, highly sensitive biosensors developed from excellent novel nanomaterials are discussed through a selective overview of recently reported researches. We also suggest creative breakthroughs for the development of next-generation biosensors using the novel nanomaterials for detecting harmful target molecules with high sensitivity.
Denture Base Composites: Effect of Surface Modified Nano- and Micro-Particulates on Mechanical Properties of Polymethyl Methacrylate
Authors: Nejatian Touraj , Nathwani Neil , Taylor Louise , Sefat Farshid
Published: January 2020

The most commonly used denture base material, polymethyl methacrylate, lacks ideal mechanical properties, which are reflected in its relatively high failure rate. Several methods have been explored to reinforce the material and reduce the cost of denture repair and replacement. In this study, various surface modified filler particles at different concentrations were dispersed in conventional and high-impact denture base materials and tested for their improvement in mechanical properties. Inorganic filler particles were coated with different silane coupling agents using an ultrasonic device. The particulates were dispersed in the resin and the composites polymerised through an innovative dual-cure technique. Charpy impact test, single-edge notch three-point bend fracture toughness test and Biaxial Flexural Strength (BFS) were performed on the specimens. The results showed that mechanical properties of the denture base resin can be improved by incorporating filler particles; however, the surface characteristics, quantity and level of dispersion of the particles play critical role in the mechanical behaviour of the composites. The results of this study are a promising step towards developing more fracture-resistant denture base materials.