bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Bullying and Cyberbullying in the Psychological Adjustment of Victims and Aggressors in Adolescence
Authors: Estévez Estefanía , Estévez Jesús F. , Segura Lucía , Suárez Cristian
Published: June 2019

The objective of the present study was to analyze the extent to which violent peer behavior and victimization, both traditional and cybernetic, and predict certain indicators of psychological maladjustment in adolescents, such as self-concept, satisfaction with life, feeling of loneliness, depressive symptomatology, perceived stress, social anxiety, empathy, and emotional intelligence. Participants in the study were 1318 adolescents of both sexes, aged between 11 and 18 years and enrolled in Compulsory Secondary Education schools. The design of the study was cross-sectional. The results indicated that the victims generally present greater maladjustment than the aggressors. Both victims and cybervictims showed a greater decrease in all the dimensions of self-concept, compared with aggressors and cyberaggressors. However, the two types of aggressors showed a higher likelihood of presenting low levels of empathy. Feeling of loneliness, depressive symptomatology, perceived stress, and degree of life satisfaction was more probable to be present in all groups of aggressors and victims. Finally, with regard to emotional intelligence, victims had a higher probability of obtaining low scores in all the dimensions of this construct; this was the case for traditional aggressors only in the dimension of emotion regulation. These results contribute to our understanding of the consequences of harassment in the adaptation of the students involved, with relevant practical implications.
Spatio-Temporal Change Characteristics of Spatial-Interaction Networks: Case Study within the Sixth Ring Road of Beijing, China
Authors: Yang Jing , Yi Disheng , Qiao Bowen , Zhang Jing
Published: June 2019

Spatial-interaction networks are an important factor in geography that could help in the exploration of both human spatial-temporal behavior and the structure of urban areas. This paper analyzes changes in the spatio-temporal characteristics of the Spatial-Interaction Networks of Beijing (SINB) in three consecutive steps. To begin with, we constructed 24 sequential snapshots of spatial population interactions on the basis of points of interest (POIs) collected from Dianping.com and various taxi GPS data in Beijing. Then, we used Jensen–Shannon distance and hierarchical clustering to integrate the 24 sequential network snapshots into four clusters. Finally, we improved the weighted k-core decomposition method by combining the complex network method and weighted distance in a geographic space. The results showed: (1) There are three layers in the SINB: a core layer, a bridge layer, and a periphery layer. The number of places greatly varies, and the SINB show an obvious hierarchical structure at different periods. The core layer contains fewer places that are between the Second and Fifth Ring Road in Beijing. Moreover, spatial distribution of places in the bridge layer is always in the same location as that of the core layer, and the quantity in the bridge layer is always superior to that in the core layer. The distributions of places in the periphery layer, however, are much greater and wider than the other two layers. (2) The SINB connected compactly over time, bearing much resemblance to a small-world network. (3) Two patterns of connection, each with different connecting ratios between layers, appear on weekdays and weekends, respectively. Our research plays a vital role in understanding urban spatial heterogeneity, and helps to support decisions in urban planning and traffic management.
A New Agent-Based Methodology for the Seismic Vulnerability Assessment of Urban Areas
Authors: Greco Annalisa , Pluchino Alessandro , Barbarossa Luca , Barreca Giovanni , Caliò Ivo , Martinico Francesco , Rapisarda Andrea
Published: June 2019

In order to estimate the seismic vulnerability of a densely populated urban area, it would in principle be necessary to evaluate the dynamic behaviour of individual and aggregate buildings. These detailed seismic analyses, however, are extremely cost-intensive and require great processing time and expertise judgment. The aim of the present study is to propose a new methodology able to combine information and tools coming from different scientific fields in order to reproduce the effects of a seismic input in urban areas with known geological features and to estimate the entity of the damages caused on existing buildings. In particular, we present a new software called ABES (Agent-Based Earthquake Simulator), based on a Self-Organized Criticality framework, which allows to evaluate the effects of a sequence of seismic events on a certain large urban area during a given interval of time. The integration of Geographic Information System (GIS) data sets, concerning both geological and urban information about the territory of Avola (Italy), allows performing a parametric study of these effects on a real context as a case study. The proposed new approach could be very useful in estimating the seismic vulnerability and defining planning strategies for seismic risk reduction in large urban areas
Current Trends and Future Perspective of Mesenchymal Stem Cells and Exosomes in Corneal Diseases
Authors: Mansoor Hassan , Ong Hon Shing , Riau Andri K. , Stanzel Tisha P. , Mehta Jodhbir S. , Yam Gary Hin-Fai
Published: June 2019

The corneal functions (transparency, refractivity and mechanical strength) deteriorate in many corneal diseases but can be restored after corneal transplantation (penetrating and lamellar keratoplasties). However, the global shortage of transplantable donor corneas remains significant and patients are subject to life-long risk of immune response and graft rejection. Various studies have shown the differentiation of multipotent mesenchymal stem cells (MSCs) into various corneal cell types. With the unique properties of immunomodulation, anti-angiogenesis and anti-inflammation, they offer the advantages in corneal reconstruction. These effects are widely mediated by MSC differentiation and paracrine signaling via exosomes. Besides the cell-free nature of exosomes in circumventing the problems of cell-fate control and tumorigenesis, the vesicle content can be genetically modified for optimal therapeutic affinity. The pharmacology and toxicology, xeno-free processing with sustained delivery, scale-up production in compliant to Good Manufacturing Practice regulations, and cost-effectiveness are the current foci of research. Routes of administration via injection, topical and/or engineered bioscaffolds are also explored for its applicability in treating corneal diseases.
Comprehensive Analysis of lncRNAs and circRNAs Reveals the Metabolic Specialization in Oxidative and Glycolytic Skeletal Muscles
Authors: Shen Linyuan , Gan Mailin , Tang Qianzi , Tang Guoqing , Jiang Yanzhi , Li Mingzhou , Chen Lei , Bai Lin , Shuai Surong , Wang Jinyong , Li Xuewei , Liao Kun , Zhang Shunhua , Zhu Li
Published: June 2019

The biochemical and functional differences between oxidative and glycolytic muscles could affect human muscle health and animal meat quality. However, present understanding of the epigenetic regulation with respect to lncRNAs and circRNAs is rudimentary. Here, porcine oxidative and glycolytic skeletal muscles, which were at the growth curve inflection point, were sampled to survey variant global expression of lncRNAs and circRNAs using RNA-seq. A total of 4046 lncRNAs were identified, including 911 differentially expressed lncRNAs (p < 0.05). The cis-regulatory analysis identified target genes that were enriched for specific GO terms and pathways (p < 0.05), including the oxidation-reduction process, glycolytic process, and fatty acid metabolic. All these were closely related to different phenotypes between oxidative and glycolytic muscles. Additionally, 810 circRNAs were identified, of which 137 were differentially expressed (p < 0.05). Interestingly, some circRNA-miRNA-mRNA networks were found, which were closely linked to muscle fiber-type switching and mitochondria biogenesis in muscles. Furthermore, 44.69%, 39.19%, and 54.01% of differentially expressed mRNAs, lncRNAs, and circRNAs respectively were significantly enriched in pig quantitative trait loci (QTL) regions for growth and meat quality traits. This study reveals a mass of candidate lncRNAs and circRNAs involved in muscle physiological functions, which may improve understanding of muscle metabolism and development from an epigenetic perspective.
Experimental Approaches and Computational Modeling of Rat Serum Albumin and Its Interaction with Piperine
Authors: Zazeri Gabriel , Povinelli Ana , Lima Marcelo , Cornélio Marinônio
Published: June 2019

The bioactive piperine (1-piperoyl piperidine) compound found in some pepper species (Piper nigrum linn and Piper sarmentosum Roxb) has been shown to have therapeutic properties and to be useful for well-being. The tests used to validate these properties were performed in vitro or with small rats. However, in all these assays, the molecular approach was absent. Although the first therapeutic trials relied on the use of rats, no proposal was mentioned either experimentally or computationally at the molecular level regarding the interaction between piperine and rat serum albumin (RSA). In the present study, several spectroscopic techniques were employed to characterize rat serum albumin and, aided by computational techniques, the protein modeling was proposed. From the spectroscopic results, it was possible to estimate the binding constant (3.9 × 104 M−1 at 288 K) using the Stern–Volmer model and the number of ligands (three) associated with the protein applying interaction density function model. The Gibbs free energy, an important thermodynamic parameter, was determined (−25 kJ/mol), indicating that the interaction was spontaneous. This important set of experimental results served to parameterize the computational simulations. The results of molecular docking and molecular dynamics matched appropriately made it possible to have detailed microenvironments of RSA accessed by piperine.
Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress
Authors: Hua Lingyue , Wu Na , Zhao Ruilin , He Xuanhong , Liu Qian , Li Xiatian , He Zhiqiang , Yu Lehan , Yan Nianlong
Published: June 2019

Endothelial dysfunction (ED) is an important contributor to atherosclerotic cardiovascular disease. Our previous study demonstrated that sphingomyelin synthase 2 (SMS2) promotes ED. Moreover, endoplasmic reticulum (ER) stress can lead to ED. However, whether there is a correlation between SMS2 and ER stress is unclear. To examine their correlation and determine the detailed mechanism of this process, we constructed a human umbilical vein endothelial cell (HUVEC) model with SMS2 overexpression. These cells were treated with 4-PBA or simvastatin and with LiCl and salinomycin alone. The results showed that SMS2 can promote the phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and activate the Wnt/β-catenin pathway and that activation or inhibition of the Wnt/β-catenin pathway can induce or block ER stress, respectively. However, inhibition of ER stress by 4-PBA can decrease ER stress and ED. Furthermore, when the biosynthesis of cholesterol is inhibited by simvastatin, the reduction in intracellular cholesterol coincides with a decrease in ER stress and ED. Collectively, our results demonstrate that SMS2 can activate the Wnt/β-catenin pathway and promote intracellular cholesterol accumulation, both of which can contribute to the induction of ER stress and finally lead to ED.
Adipose Tissue, Obesity and Adiponectin: Role in Endocrine Cancer Risk
Authors: Tumminia Andrea , Vinciguerra Federica , Parisi Miriam , Graziano Marco , Sciacca Laura , Baratta Roberto , Frittitta Lucia
Published: June 2019

Adipose tissue has been recognized as a complex organ with endocrine and metabolic roles. The excess of fat mass, as occurs during overweight and obesity states, alters the regulation of adipose tissue, contributing to the development of obesity-related disorders. In this regard, many epidemiological studies shown an association between obesity and numerous types of malignancies, comprising those linked to the endocrine system (e.g., breast, endometrial, ovarian, thyroid and prostate cancers). Multiple factors may contribute to this phenomenon, such as hyperinsulinemia, dyslipidemia, oxidative stress, inflammation, abnormal adipokines secretion and metabolism. Among adipokines, growing interest has been placed in recent years on adiponectin (APN) and on its role in carcinogenesis. APN is secreted by adipose tissue and exerts both anti-inflammatory and anti-proliferative actions. It has been demonstrated that APN is drastically decreased in obese individuals and that it can play a crucial role in tumor growth. Although literature data on the impact of APN on carcinogenesis are sometimes conflicting, the most accredited hypothesis is that it has a protective action, preventing cancer development and progression. The aim of the present review is to summarize the currently available evidence on the involvement of APN and its signaling in the etiology of cancer, focusing on endocrine malignancies.
A Profile of the In Vitro Anti-Tumor Activity and In Silico ADME Predictions of Novel Benzothiazole Amide-Functionalized Imidazolium Ionic Liquids
Authors: Al-blewi Fawzia , Rezki Nadjet , Naqvi Arshi , Qutb Uddin Husna , Al-Sodies Salsabeel , Messali Mouslim , Aouad Mohamed Reda , Bardaweel Sanaa
Published: June 2019

A focused array of green imidazolium ionic liquids (ILs) encompassing benzothiazole ring and amide linkage were designed and synthesized using quaternization and metathesis protocols. The synthesized ILs have been fully characterized by usual spectroscopic methods and screened for their anticancer activities against human cancer cell lines originating from breast and colon cancers. Collectively, our biological data demonstrate that the newly synthesized series has variable anticancer activities in the examined cancer types. The synthesized ILs 8, 10 and 21–29 comprising the methyl and methyl sulfonyl benzothiazole ring emerged as the most potent compounds with promising antiproliferative activities relative to their benzothiazole ring counterparts. Furthermore, the mechanism underlying the observed anticancer activity was investigated. The most active compound 22 appears to exert its anticancer effect through apoptosis dependent pathway in breast cancer cells. Interestingly, compound 22 has also shown good in silico absorption (81.75%) along with high gastro-intestinal absorption as per ADME predictions.
Role of Major Endocannabinoid-Binding Receptors during Mouse Oocyte Maturation
Authors: Cecconi Sandra , Rossi Gianna , Oddi Sergio , Di Nisio Valentina , Maccarrone Mauro
Published: June 2019

Endocannabinoids are key-players of female fertility and potential biomarkers of reproductive dysfunctions. Here, we investigated localization and expression of cannabinoid receptor type-1 and -2 (CB1R and CB2R), G-protein coupled receptor 55 (GPR55), and transient receptor potential vanilloid type 1 channel (TRPV1) in mouse oocytes collected at different stages of in vivo meiotic maturation (germinal vesicle, GV; metaphase I, MI; metaphase II, MII) through qPCR, confocal imaging, and western blot. Despite the significant decrease in CB1R, CB2R, and GPR55 mRNAs occurring from GV to MII, CB2R and GPR55 protein contents increased during the same period. At GV, only CB1R was localized in oolemma, but it completely disappeared at MI. TRPV1 was always undetectable. When oocytes were in vitro matured with CB1R and CB2R but not GPR55 antagonists, a significant delay of GV breakdown occurred, sustained by elevated intraoocyte cAMP concentration. Although CBRs antagonists did not affect polar body I emission or chromosome alignment, GPR55 antagonist impaired in ~75% of oocytes the formation of normal-sized MI and MII spindles. These findings open a new avenue to interrogate oocyte pathophysiology and offer potentially new targets for the therapy of reproductive alterations.
Overexpression of a Metallothionein 2A Gene from Date Palm Confers Abiotic Stress Tolerance to Yeast and Arabidopsis thaliana
Authors: Patankar Himanshu V. , Al-Harrasi Ibtisam , Al Kharusi Latifa , Jana Gerry Aplang , Al-Yahyai Rashid , Sunkar Ramanjulu , Yaish Mahmoud W.
Published: June 2019

Although the date palm tree is an extremophile with tolerance to drought and certain levels of salinity, the damage caused by extreme salt concentrations in the soil, has created a need to explore stress-responsive traits and decode their mechanisms. Metallothioneins (MTs) are low-molecular-weight cysteine-rich proteins that are known to play a role in decreasing oxidative damage during abiotic stress conditions. Our previous study identified date palm metallothionein 2A (PdMT2A) as a salt-responsive gene, which has been functionally characterized in yeast and Arabidopsis in this study. The recombinant PdMT2A protein produced in Escherichia coli showed high reactivity against the substrate 5′-dithiobis-2-nitrobenzoic acid (DTNB), implying that the protein has the property of scavenging reactive oxygen species (ROS). Heterologous overexpression of PdMT2A in yeast (Saccharomyces cerevisiae) conferred tolerance to drought, salinity and oxidative stresses. The PdMT2A gene was also overexpressed in Arabidopsis, to assess its stress protective function in planta. Compared to the wild-type control, the transgenic plants accumulated less Na+ and maintained a high K+/Na+ ratio, which could be attributed to the regulatory role of the transgene on transporters such as HKT, as demonstrated by qPCR assay. In addition, transgenic lines exhibited higher chlorophyll content, higher superoxide dismutase (SOD) activity and improved scavenging ability for reactive oxygen species (ROS), coupled with a better survival rate during salt stress conditions. Similarly, the transgenic plants also displayed better drought and oxidative stress tolerance. Collectively, both in vitro and in planta studies revealed a role for PdMT2A in salt, drought, and oxidative stress tolerance.
Src and ROCK Kinases Differentially Regulate Mineralization of Human Osteosarcoma Saos-2 Cells
Authors: Strzelecka-Kiliszek Agnieszka , Romiszewska Marta , Bozycki Lukasz , Mebarek Saida , Bandorowicz-Pikula Joanna , Buchet Rene , Pikula Slawomir
Published: June 2019

Osteoblasts initiate bone mineralization by releasing matrix vesicles (MVs) into the extracellular matrix (ECM). MVs promote the nucleation process of apatite formation from Ca2+ and Pi in their lumen and bud from the microvilli of osteoblasts during bone development. Tissue non-specific alkaline phosphatase (TNAP) as well as annexins (among them, AnxA6) are abundant proteins in MVs that are engaged in mineralization. In addition, sarcoma proto-oncogene tyrosine-protein (Src) kinase and Rho-associated coiled-coil (ROCK) kinases, which are involved in vesicular transport, may also regulate the mineralization process. Upon stimulation in osteogenic medium containing 50 μg/mL of ascorbic acid (AA) and 7.5 mM of β-glycerophosphate (β-GP), human osteosarcoma Saos-2 cells initiated mineralization, as evidenced by Alizarin Red-S (AR-S) staining, TNAP activity, and the partial translocation of AnxA6 from cytoplasm to the plasma membrane. The addition of 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d] pyrimidine (PP2), which is an inhibitor of Src kinase, significantly inhibited the mineralization process when evaluated by the above criteria. In contrast, the addition of (R)-(+)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide hydrochloride (Y-27632), which is an inhibitor of ROCK kinase, did not affect significantly the mineralization induced in stimulated Saos-2 cells as denoted by AR-S and TNAP activity. In conclusion, mineralization by human osteosarcoma Saos-2 cells seems to be differently regulated by Src and ROCK kinases.
Theoretical Analysis for Wireless Magnetothermal Deep Brain Stimulation Using Commercial Nanoparticles
Authors: Le Tuan-Anh , Bui Minh Phu , Yoon Jungwon
Published: June 2019

A wireless magnetothermal stimulation (WMS) is suggested as a fast, tetherless, and implanted device-free stimulation method using low-radio frequency (100 kHz to 1 MHz) alternating magnetic fields (AMF). As magnetic nanoparticles (MNPs) can transduce alternating magnetic fields into heat, they are targeted to a region of the brain expressing the temperature-sensitive ion channel (TRPV1). The local temperature of the targeted area is increased up to 44 °C to open the TRPV1 channels and cause an influx of Ca2+ sensitive promoter, which can activate individual neurons inside the brain. The WMS has initially succeeded in showing the potential of thermomagnetics for the remote control of neural cell activity with MNPs that are internally targeted to the brain. In this paper, by using the steady-state temperature rise defined by Fourier’s law, the bio-heat equation, and COMSOL Multiphysics software, we investigate most of the basic parameters such as the specific loss power (SLP) of MNPs, the injection volume of magnetic fluid, stimulation and cooling times, and cytotoxic effects at high temperatures (43–44 °C) to provide a realizable design guideline for WMS.
An Intelligent Spam Detection Model Based on Artificial Immune System
Authors: Saleh Abdul Jabbar , Karim Asif , Shanmugam Bharanidharan , Azam Sami , Kannoorpatti Krishnan , Jonkman Mirjam , Boer Friso De
Published: June 2019

Spam emails, also known as non-self, are unsolicited commercial or malicious emails, sent to affect either a single individual or a corporation or a group of people. Besides advertising, these may contain links to phishing or malware hosting websites set up to steal confidential information. In this paper, a study of the effectiveness of using a Negative Selection Algorithm (NSA) for anomaly detection applied to spam filtering is presented. NSA has a high performance and a low false detection rate. The designed framework intelligently works through three detection phases to finally determine an email’s legitimacy based on the knowledge gathered in the training phase. The system operates by elimination through Negative Selection similar to the functionality of T-cells’ in biological systems. It has been observed that with the inclusion of more datasets, the performance continues to improve, resulting in a 6% increase of True Positive and True Negative detection rate while achieving an actual detection rate of spam and ham of 98.5%. The model has been further compared against similar studies, and the result shows that the proposed system results in an increase of 2 to 15% in the correct detection rate of spam and ham.
Determination of pKa Values via ab initio Molecular Dynamics and its Application to Transition Metal-Based Water Oxidation Catalysts
Authors: Schilling Mauro , Luber Sandra
Published: June 2019

The p K a values are important for the in-depth elucidation of catalytic processes, the computational determination of which has been challenging. The first simulation protocols employing ab initio molecular dynamics simulations to calculate p K a values appeared almost two decades ago. Since then several slightly different methods have been proposed. We compare the performance of various evaluation methods in order to determine the most reliable protocol when it comes to simulate p K a values of transition metal-based complexes, such as the here investigated Ru-based water oxidation catalysts. The latter are of high interest for sustainable solar-light driven water splitting, and understanding of the underlying reaction mechanism is crucial for their further development.
Development of a Neutron Imaging Station at the n_TOF Facility of CERN and Applications to Beam Intercepting Devices
Authors: Mingrone Federica , Calviani Marco , Torregrosa Martin Claudio , Aberle Oliver , Bacak Michael , Chiaveri Enrico , Fornasiere Elvis , Perillo-Marcone Antonio , Vlachoudis Vasilis ,   the n_TOF Collaboration
Published: June 2019

A neutron radiography testing station has been developed exploiting the neutron beam of CERN’s n_TOF Experimental Area 2, located at the shortest distance to the neutron producing-target. The characteristics of the n_TOF neutron beam for the imaging setup are presented in this paper, together with the obtained experimental results. The results focused on the testing of several particle producing targets, including a spent antiproton production targets as well as targets from two different HiRadMat’s experiments. The possible developments of neutron imaging capabilities of the n_TOF facility in terms of detection-systems and beam-line upgrades are as well outlined.
Clinical Value of Whole Blood Procalcitonin Using Point of Care Testing, Quick Sequential Organ Failure Assessment Score, C-Reactive Protein and Lactate in Emergency Department Patients with Suspected Infection
Authors: Shim Bo-Sun , Yoon Young-Hoon , Kim Jung-Youn , Cho Young-Duck , Park Sung-Jun , Lee Eu-Sun , Choi Sung-Hyuk
Published: June 2019

We investigated the clinical value of whole blood procalcitonin using point of care testing, quick sequential organ failure assessment score, C-reactive protein and lactate in emergency department patients with suspected infection and assessed the accuracy of the whole blood procalcitonin test by point-of-care testing. Participants were randomly selected from emergency department patients who complained of a febrile sense, had suspected infection and underwent serum procalcitonin testing. Whole blood procalcitonin levels by point-of-care testing were compared with serum procalcitonin test results from the laboratory. Participants were divided into two groups—those with bacteremia and those without bacteremia. Sensitivity, specificity, positive predictive value, negative predictive value of procalcitonin, lactate and Quick Sepsis-related Organ Failure Assessment scores were investigated in each group. Area under receiving operating curve of C-reactive protein, lactate and procalcitonin for predicting bacteremia and 28-day mortality were also evaluated. Whole blood procalcitonin had an excellent correlation with serum procalcitonin. The negative predictive value of procalcitonin and lactate was over 90%. Area under receiving operating curve results proved whole blood procalcitonin to be fair in predicting bacteremia or 28-day mortality. In the emergency department, point-of-care testing of whole blood procalcitonin is as accurate as laboratory testing. Moreover, procalcitonin is a complementing test together with lactate for predicting 28-days mortality and bacteremia for patients with suspected infection.
Parathyroid Hormone-Related Protein (PTHrP) Accelerates Soluble RANKL Signals for Downregulation of Osteogenesis of Bone Mesenchymal Stem Cells
Authors: Elango Jeevithan , Rahman Saeed Ur , Henrotin Yves , de Val José Eduardo Maté Sánchez , Bao Bin , Wang Shujun , Li Bailin , Wu Wenhui
Published: June 2019

A recent study reported the expression of receptor activator of nuclear factor-κB (RANK) in mesenchymal stem cells (MSCs) surface that negatively regulates osteogenesis of MSCs. Empirical evidence from the previous study confirmed the role of parathyroid hormone-related protein (PTHrP) in osteoblastogenesis. However, it is necessary to understand the paracrine role of PTHrP and RANKL for osteogenesis in order to explore the hidden secrets in bone biology. Considering the above concept, paracrine cues of soluble-receptor activator of nuclear factor-κB ligand (sRANKL) and PTHrP in osteogenic differentiation of MSCs were investigated. Our results confirmed that sRANKL increased the expression of surface-RANK in MSCs at the earlier stage of osteogenesis, which was downregulated later in differentiated MSCs. In contrast, RANKL expression was low at the earlier stage of MSCs proliferation and high at the differentiation stage of MSCs, which may play a fundamental role in osteoclast formation. sRANKL downregulated osteogenesis of MSCs by decreasing progressive ankylosis (ANK) protein expression while PTHrP upregulated the osteogenic exploitive effect of sRANKL. Interestingly, when they were co-cultured with MSCs, T-lymphocytes expressed high membrane-RANKL levels that contribute to osteogenesis inhibition during MSC differentiation. Thus, our results disclose that sRANKL treatment downregulates osteogenesis of MSCs by increasing RANK expression at the earlier stage of differentiation and by inhibiting ANK. Further, we demonstrated that PTHrP accelerated the downregulating osteogenic effect of sRANKL.
Salivary Redox Biomarkers in Different Stages of Dementia Severity
Authors: Klimiuk Anna , Maciejczyk Mateusz , Choromańska Magdalena , Fejfer Katarzyna , Waszkiewicz Napoleon , Zalewska Anna
Published: June 2019

This study is the first to evaluate oxidative stress biomarkers in saliva/blood of patients with varying degrees of dementia progression. The study included 50 healthy controls and 50 dementia patients divided into two groups: those with mild and moderate dementia (MMSE 11–23) and patients suffering from severe dementia (MMSE 0–10). Cognitive functions of the subjects were assessed using the Mini Mental State Examination (MMSE). Enzymatic and non-enzymatic antioxidants, oxidative damage products and protein glycoxidative modifications were determined in non-stimulated (NWS) and stimulated (SWS) saliva as well as erythrocyte/plasma samples. Generally, in dementia patients, we observed the depletion of antioxidant defences leading to oxidative and glycoxidative damage in NWS, SWS and blood samples. Both salivary and blood oxidative stress increased with the severity of the disease, and correlated with a decrease of cognitive functions. Interestingly, in dementia patients, reduced glutathione (GSH) in NWS correlated not only with the severity of dementia, but also with GSH concentration in the plasma. In receiver operating characteristic (ROC) analysis, we have demonstrated that salivary GSH clearly distinguishes patients with severe dementia from those suffering from mild or moderate dementia (area under the curve (AUC) = 1). Therefore, salivary GSH can be used as a non-invasive biomarker of cognitive impairment.
Indoleamine-2,3-Dioxygenase in Thyroid Cancer Cells Suppresses Natural Killer Cell Function by Inhibiting NKG2D and NKp46 Expression via STAT Signaling Pathways
Authors: Park Arum , Yang Yunjeong , Lee Yunhee , Kim Mi Sun , Park Young-Jun , Jung Haiyoung , Kim Tae-Don , Lee Hee Gu , Choi Inpyo , Yoon Suk Ran
Published: June 2019

Natural killer (NK) cells are key players in the immune system. They use receptors on their cell surface to identify target cells. However, to escape being killed by the immune system, cancer cells such as thyroid cancer cells, use various methods to suppress the function of NK cells. Thus, this study aims to elucidate how thyroid cancer cells downregulate NK cell function in a co-culture system. We found that thyroid cancer cells suppress NK cell cytotoxicity and inhibit the expression of activating receptors, such as NKG2D and NKp46, by regulating indoleamine 2,3-dioxygenase (IDO). Also, thyroid cancer cells produce kynurenine using IDO, which causes NK cell dysfunction. Kynurenine enters NK cells via the aryl hydrocarbon receptor (AhR) on the surfaces of the NK cells, which decreases NK cell function and NK receptor expression via the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways. In addition, STAT1 and STAT3 directly regulated the expression of NKG2D and NKp46 receptors by binding to the promoter region. Conclusively, NK cell function may be impaired in thyroid cancer patients by IDO-induced kynurenine production. This implies that IDO can be used as a target for thyroid cancer therapeutics aiming at improving NK cell function.
Interactions between Aspergillus fumigatus and Pulmonary Bacteria: Current State of the Field, New Data, and Future Perspective
Authors: Briard Benoit , Mislin Gaëtan L. A. , Latgé Jean-Paul , Beauvais Anne
Published: June 2019

Aspergillus fumigatus and Pseudomonas aeruginosa are central fungal and bacterial members of the pulmonary microbiota. The interactions between A. fumigatus and P. aeruginosa have only just begun to be explored. A balance between inhibitory and stimulatory effects on fungal growth was observed in mixed A. fumigatus–P. aeruginosa cultures. Negative interactions have been seen for homoserine-lactones, pyoverdine and pyochelin resulting from iron starvation and intracellular inhibitory reactive oxidant production. In contrast, several types of positive interactions were recognized. Dirhamnolipids resulted in the production of a thick fungal cell wall, allowing the fungus to resist stress. Phenazines and pyochelin favor iron uptake for the fungus. A. fumigatus is able to use bacterial volatiles to promote its growth. The immune response is also differentially regulated by co-infections.
The Influence of Single Lap Geometry in Adhesive and Hybrid Joints on Their Load Carrying Capacity
Authors: Golewski Przemysław , Sadowski Tomasz
Published: June 2019

The manufacturing technology for adhesive joints is not yet fully optimized, as proved by a large number of papers that have been published in recent years. Future studies on innovative techniques for fabricating adhesive joints should investigate the influence of parameters such as: (1) The shape of adhesive protrusion, (2) lap dimensions, and (3) cohesive layer reduction in the most efforted regions of the joint. With the application of additional mechanical connectors (e.g., rivets, screws, and welds) in adhesive joints, new hybrid connections can be fabricated. The number of publications in this new field is still relatively small. To fill the gap, this paper presents the results of a numerical analysis of different single lap geometries in (1) pure adhesive and (2) hybrid joints. A total of 13 different models with the same surface area of the adhesive layer were considered. In the case of hybrid joints, the adhesive surface before the application of mechanical connectors was assumed to be the same in every tested case. The numerical analysis of pure adhesive and hybrid joints revealed that the differences in strength led to a 30% decrease in the load capacity of these joints. Therefore, when designing pure adhesive and hybrid joints, special attention should be paid to the shape of the lap between the joined elements.
Refitting of Zirconia Toughening into Open-Cellular Alumina Foams by Infiltration with Zirconyl Nitrate
Authors: Betke Ulf , Scheunemann Marcel , Scheffler Michael
Published: June 2019

The present work describes the combination of the well-established dispersion infiltration of the hollow struts in reticulated porous ceramics (RPCs) and the salt solution infiltration of the remaining strut porosity. This approach is applied on alumina foams, which are loaded subsequently with a dispersion of sub-micrometer alumina particles and a ZrO(NO3)2 solution. The zirconyl nitrate is converted into a ZrO2 transformation toughening phase during the final sintering step. As a consequence of the complex microstructure evolution during the consecutive infiltration cycles, the reinforcement phase concentrates selectively at the weak spots of RPC structures—namely, the hollow strut cavities and longitudinal cracks along the struts. As a consequence, a severe improvement of the compressive strength is observed: The average compressive strength, normalized to a porosity of 91.6 vol.%, is 1.47 MPa for the Al2O3/ZrO2 infiltrated foams, which is an improvement by 40% with respect to alumina-only loaded foams (1.05 MPa) or by 206% compared to uninfiltrated alumina RPCs (0.48 MPa). The compressive strength results are correlated to infiltration parameters and the properties of the infiltration fluids, for example the rheological behavior and the size of the Zr solute species in the respective ZrO(NO3)2 solution.
Void Distribution in Zeolite Warm Mix Asphalt Mixture Based on X-ray Computed Tomography
Authors: Ren Junda , Xing Chao , Tan Yiqiu , Liu Nan , Liu Jingyi , Yang Liying
Published: June 2019

Warm mix asphalt mixtures have the advantages of energy saving, emission reduction and good road performance. Zeolite asphalt mixtures, as a warm mixing technology, have been applied in the world. To understand the warm mix mechanism of zeolite warm mix asphalt mixture, the mesoscale structure of zeolite asphalt is studied. Micro computed tomography (CT) is utilized to obtain the internal structure image of zeolite-modified asphalt and asphalt mixture. The quantity and volume of voids are used as internal void distribution evaluation indexes. The results indicate that with respect to the void distribution in zeolite-modified asphalt, with the increase of temperature, there is an obvious evolution trend of smaller voids to larger voids. With respect to the voids in the zeolite-modified asphalt mixture, the zeolite asphalt mixture is equivalent to hot mix asphalt mixture when it is above 120 °C, while below 120 °C, the maximum and average void volumes increase significantly, making it difficult for the mixture to achieve ideal compaction effect.
Rietveld Quantitative Phase Analysis of Oil Well Cement: In Situ Hydration Study at 150 Bars and 150 °C
Authors: Fraga Edmundo , Cuesta Ana , Zea-Garcia Jesus , De la Torre Angeles , Yáñez-Casal Armando , Aranda Miguel
Published: June 2019

Oil and gas well cements are multimineral materials that hydrate under high pressure and temperature. Their overall reactivity at early ages is studied by a number of techniques including through the use of the consistometer. However, for a proper understanding of the performance of these cements in the field, the reactivity of every component, in real-world conditions, must be analysed. To date, in situ high energy synchrotron powder diffraction studies of hydrating oil well cement pastes have been carried out, but the quality of the data was not appropriated for Rietveld quantitative phase analyses. Therefore, the phase reactivities were followed by the inspection of the evolution of non-overlapped diffraction peaks. Very recently, we have developed a new cell specially designed to rotate under high pressure and temperature. Here, this spinning capillary cell is used for in situ studies of the hydration of a commercial oil well cement paste at 150 bars and 150 °C. The powder diffraction data were analysed by the Rietveld method to quantitatively determine the reactivities of each component phase. The reaction degree of alite was 90% after 7 h, and that of belite was 42% at 14 h. These analyses are accurate, as the in situ measured crystalline portlandite content at the end of the experiment, 12.9 wt%, compares relatively well with the value determined ex situ by thermal analysis, i.e., 14.0 wt%. The crystalline calcium silicates forming at 150 bars and 150 °C are also discussed.
Iron(III) Azadiphenolate Compounds in a New Family of Spin Crossover Iron(II)–Iron(III) Mixed-Valent Complexes
Authors: Phonsri Wasinee , Macedo David S. , Lewis Barnaby A. I. , Wain Declan F. , Murray Keith S.
Published: June 2019

A new family of mixed valent, double salt spin crossover compounds containing anionic FeIII and cationic FeII compounds i.e., [FeII{(pz)3CH}2][FeIII(azp)2]2·2H2O (4), [FeII(TPPZ)2][FeIII(azp)2]2]·H2O (5) and [FeII(TPPZ)2][FeIII(azp)2]2]·H2O·3MeCN (6) (where (pz)3CH = tris-pyrazolylmethane, TPPZ = 2,3,5,6, tetrapyridylpyrazine and azp2− = azadiphenolato) has been synthesized and characterised. This is the first time that the rare anionic spin crossover species, [FeIII(azp)2]−, has been used as an anionic component in double salts complexes. Single crystal structures and magnetic studies showed that compound 6 exhibits a spin transition relating to one of the FeIII centres of the constituent FeII and FeIII sites. Crystal structures of the anionic and cationic precursor complexes were also analysed and compared to the double salt products thus providing a clearer picture for future crystal design in double spin crossover materials. We discuss the effects that the solvent and counterion had on the crystal packing and spin crossover properties.
Selected Applications of the Theory of Connections: A Technique for Analytical Constraint Embedding
Authors: Johnston Hunter , Leake Carl , Efendiev Yalchin , Mortari Daniele
Published: June 2019

In this paper, we consider several new applications of the recently introduced mathematical framework of the Theory of Connections (ToC). This framework transforms constrained problems into unconstrained problems by introducing constraint-free variables. Using this transformation, various ordinary differential equations (ODEs), partial differential equations (PDEs) and variational problems can be formulated where the constraints are always satisfied. The resulting equations can then be easily solved by introducing a global basis function set (e.g., Chebyshev, Legendre, etc.) and minimizing a residual at pre-defined collocation points. In this paper, we highlight the utility of ToC by introducing various problems that can be solved using this framework including: (1) analytical linear constraint optimization; (2) the brachistochrone problem; (3) over-constrained differential equations; (4) inequality constraints; and (5) triangular domains.
ESBL and AmpC β-Lactamases in Clinical Strains of Escherichia coli from Serra da Estrela, Portugal
Authors: Oliveira Cátia , Amador Paula , Prudêncio Cristina , Tomaz Cândida T , Tavares-Ratado Paulo , Fernandes Rúben
Published: June 2019

Background and Objectives: Given the considerable spatial, temporal, and ecological factors, heterogeneity, which affects emergency response, persistence, and dissemination of genetic determinants that confer microorganisms their resistance to antibiotics, several authors claim that antibiotics’ resistance must be perceived as an ecological problem. The aim of this study was to determine the prevalence of broad-spectrum bla genes, not only Extended-spectrum β-lactamases (ESBL) but also AmpC-types, in clinical strains of Escherichia coli isolated from Portugal (in the highest region of the country, Serra da Estrela) to disclose susceptibility profiles among different genotypes, and to compare the distribution of bla genes expressing broad-spectrum enzymes. Materials and Methods: Clinical strains of Escherichia coli presenting resistance to third generation (3G) cephalosporins and susceptibility to inhibition by clavulanic acid were studied by means of phenotypic and molecular profiling techniques for encoding β-lactamases genes. Results: Strains were mainly isolated from hospital populations (97%). Molecular analysis enabled the detection of 49 bla genes, in which 55% (27/49) were identified as blaOXA-1-like, 33% (16/49) as blaCTX-M-group-1, 10% (5/49) as blaTEM, and 2% (1/49) were identified as genes blaCIT (AmpC). Among all blaOXA-1-like detected, about 59% of strains expressed at least another bla gene. Co-production of β-lactamases was observed in 40% of strains, with the co-production of CTX-M group 1 and OXA-1-like occurring as the most frequent. Conclusions: This is the first study using microorganisms isolated from native people from the highest Portuguese mountain regions, showing an unprecedent high prevalence of genes blaOXA-1-like in this country.
Amorphous Steel Coatings Deposited by Cold-Gas Spraying
Authors: Tului Mario , Bartuli Cecilia , Bezzon Alessia , Marino Angelo Luigi , Marra Francesco , Matera Susanna , Pulci Giovanni
Published: June 2019

Cold-gas spray (CGS) deposition of amorphous steel coatings starting from a commercial feedstock powder containing boron, tungsten, and silicon was investigated. Microstructural characterization, carried out by X-ray diffraction (XRD), transmission electron microscopy, and backscattered electron diffraction (EBSD) analysis, confirmed the amorphous nature of deposited coatings. The amorphization phenomenon is related to high-strain/strain-rate deformation with shear instability caused by very high particle kinetic energy, with a mechanism that resembles the severe plastic deformation process. The CGS coatings were heat-treated at temperatures ranging from 650 to 850 °C to induce partial recrystallization. The effect of nanocrystal nucleation and growth on the hardness of the coatings was investigated, and the hardness of heat-treated samples was found to increase with respect to as-sprayed coatings, outperforming conventional high-velocity oxy-fuel (HVOF) deposits. Hardness was found to decrease after prolonged (<90 min) or higher temperature (>750 °C) exposures.
Microfluidic Technology for Clinical Applications of Exosomes
Authors: Iliescu Florina , Vrtačnik Danilo , Neuzil Pavel , Iliescu Ciprian
Published: June 2019

Exosomes, a type of nanovesicle, are distinct cellular entities specifically capable of carrying various cargos between cells. It has been hypothesized that exosomes, as an enriched source of biomolecules, may serve as biomarkers for various diseases. This review introduces general aspects of exosomes, presents the challenges in exosome research, discusses the potential of exosomes as biomarkers, and describes the contribution of microfluidic technology to enable their isolation and analysis for diagnostic and disease monitoring. Additionally, clinical applications of exosomes for diagnostic purposes are also summarized.
Structural Characterizations of Aluminosilicates in Two Types of Fly Ash Samples from Shanxi Province, North China
Authors: Liu Yunxia , Zeng Fangui , Sun Beilei , Jia Peng , Graham Ian T.
Published: June 2019

In order to determine the structural characterization of aluminosilicates in two types of fly ashes, two samples from Shanxi Province, China were selected for study. One was from a pulverized coal boiler (FA-1), and the other from a circulating fluidized bed boiler (FA-2). FA-1 had a much higher content of silicon dioxide (SiO2) (70.30%) than FA-2(42.19%), but aluminum oxide (Al2O3) was higher in FA-2 (25.41%) than in FA-1 (17.04%). The characterizations were investigated using various methods including X-ray diffraction (XRD), Fourier transform infrared spectrometry (FTIR), magic angle spinning nuclear magnetic resonance (MAS–NMR) spectrometry, and X-ray photoelectron spectroscopy (XPS). The XRD analysis showed that FA-1 contained aluminosilicate glass, quartz and mullite, while FA-2 contained significant amounts of amorphous aluminosilicate, quartz and gypsum. The FTIR results showed an increased substitution of Al3+ for Si4+ as the band of asymmetric stretching vibrations Si–O(Si) (1100 cm−1) moved to 1090 cm−1 for FA-2, much lower than for FA-1(1097 cm−1). Moreover, the sharpness of the bands in the 1250–1000 cm−1 region for FA-2 indicates that the silicate structure of FA-2 was more ordered than for FA-1. It can be understood from the 29Si MAS–NMR results that Q4(mAl) (Q4 are connected via 4 bridging O atoms to mAl) is the main structural type in FA-1 and FA-2, and that FA-2 contains more Al, which substitutes for Si in the Q4 structure. 27Al MAS–NMR demonstrated that a combination of tetrahedral, pentahedral, and octahedral Al existed in FA-1 and FA-2. The Si 2p XPS spectra suggested that there were three forms of Si, including bridging Si (Si–O2), non–bridging Si (Si–O), and SiO2 gel. The content of Si–O2 for FA-1 was 37.48% higher than Si–O (28.57%), while the content of Si–O2 was 30.21% lower than Si–O (40.15%) for FA-2. The Al 2p XPS spectra showed that octahedral Al was the dominant form for FA-1 with a content of 40.25%, while the main phase was tetrahedral Al for FA-2 with a proportion of 37.36%, which corresponds well with the 27Al MAS–NMR results.