bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic Administration of miRNA Mimics by Liposomal Delivery System in Animal Model of Colorectal Carcinoma
Authors: MERHAUTOVÁ J. , VYCHYTILOVÁ-FALTEJSKOVÁ P. , DEMLOVÁ R. , SLABÝ O.
Published: March 2020

MiRNAs are important regulators of gene expression and changes in their levels are linked with various pathological states, including solid tumors. MiR-215 has been identified as a tumor suppressor in colorectal cancer (CRC). Following our previous in vitro and in vivo experiments, the aim of this project was to study the possibility of increasing the levels of miR-215 in tumor cells by systemic administration of miRNA mimics in liposomal delivery system in vivo. By subcutaneous xenotransplantation of human cancer cells to NSG mice, CRC model was established. The treatment [miR-215 mimics in liposomes (20 and 40 μg/mouse), control oligonucleotide in liposomes, or saline] was administered repeatedly by i.v. injection via tail-vein. Animals were sacrificed, tumor were dissected and measured by a caliper. Expression of miR-215 in tumors, lungs and liver was quantified by RT-PCR. There was no significant differences in tumor volume and miR-215 expression between all three treatment groups. Therefore, the decrease in tumor volume was not achieved. By comparing the levels of miR-215 in lungs, liver and tumors after the treatment, we suggest that the liposomes are accumulated in the lungs and do not concentrate sufficiently in the tumor site to exert significant tumor-suppressive effect.
Gastric Cancer Cell-Derived Exosomal microRNA-23a Promotes Angiogenesis by Targeting PTEN
Authors: Du Jiang , Liang Yuan , Li Ji , Zhao Jin-Ming , Lin Xu-Yong
Published: March 2020

Hypoxia-exposed lung cancer-released exosomal microRNA-23a (miR-23a) has been shown to enhance angiogenesis as well as vascular permeability, contributing to the close correlation between exosomal miR-23a and tumorigenesis. The current study aimed to investigate whether gastric cancer (GC) cell-derived exosomal miR-23a could induce angiogenesis and to elucidate the potential mechanisms associated with the process. Differentially expressed miRNAs in GC were initially screened from the Gene Expression Omnibus database. Target genes were selected following miRNA-mRNA prediction and subsequently verified by dual luciferase reporter assay. RT-qPCR was conducted to detect miR-23a and PTEN expression in GC tissues, cells and exosomes. Human umbilical venous endothelial cells (HUVECs) were co-cultured with GC cell-derived exosomes to assess the angiogenesis mediated by exosomes in vitro. Additionally, PTEN was overexpressed in HUVECs to analyze the mechanism by which miR-23a regulates angiogenesis. miR-23a was highly expressed in GC tissues and cells and GC cell-derived exosomes. Angiogenesis was promoted by the co-culture of HUVECs and GC cells-derived exosomes, as evidenced by the increased expression of VEGF but decreased expression of TSP-1. PTEN was targeted by miR-23a and was lowly expressed in GC tissues. In a co-culture system, miR-23a carried by GC cells-derived exosomes promoted angiogenesis via the repression of PTEN. Collectively, GC cell-derived exosomal miR-23a could promote angiogenesis and provide blood supply for growth of GC cells. This study contributes to advancement of miRNA-targeted therapeutics.
New Evaluation of Small Farms: Implication for an Analysis of Food Security
Authors: Ardakani Zahra , Bartolini Fabio , Brunori Gianluca
Published: March 2020

Farm structure is a multi-dimensional concept that can be measured through different criteria. Meanwhile, farm structure has been identified to discern small farms or well-endowed farms from the other farms. Distinguishing and identifying these two groups have practical implications for understanding the dynamics in rural areas and the effectiveness of target measures in these categories. The existing literature lacks a better definition of small farms based on the different criteria used. In this paper, we have developed composite indicators to apply to the concept of farm structure to re-define small farms and discover their role in achieving food security in Europe. By clustering countries using the composite indicator of farm structure, we estimate that more than 80 percent of food across Europe is produced by multi-criteria small and medium farms, but the partial productivities of agricultural land and labor in these countries that have the majority of multi-criteria small and medium farms are much lower than the large ones. Then, an estimate of a spatial econometric regression model was done to recognize how farm structure, a representative of farm size, can affect food availability, which is representative of food security. The results show that improving the structure of farms in a country not only improves its food security but also improves its neighbors’ food security. Hence, improving the structure of multi-criteria small farms is a major part of the solution to improve and achieve food security. Recognizing and understanding the diversity of multi-criteria small farms by considering the specific products and countries is necessary for designing appropriate innovations and policies for supporting more productive multi-criteria small farms.
The Spatial Distribution, Contamination Status and Contributing Factors of Heavy Metals in Cropland Soils of Twelve Cities in Shandong Province, China
Authors: Xue Weina , Peng Yanbo , Jiang Aixia , Chen Taiyu , Cheng Jiemin
Published: March 2020

The aims of this study were to analyze the spatial distributions of, contamination statuses of, and factors contributing to, heavy metals in cropland areas of different cities; thus, 55 agricultural soils were collected from 12 cities of Shandong Province, China. Concentrations of copper (Cu), lead (Pb), cadmium (Cd), chromium (Cr), nickel (Ni) and zinc (Zn) were determined. Results showed that average contents of Cu, Pb, Cd, Cr, Ni and Zn were 24.13, 31.77, 0.16, 130.63, 22.13, and 71.19 mg·kg−1, respectively, and Pb and Cd had similar spatial distributions in those cities. Specifically, contents of Cr in cities of Weifang, Weihai, Yantai and Zibo were significantly higher than it in other cities; Weihai and Zibo also had significantly high contents of Zn. Moreover, concentrations of Cr in brown soils and cinnamon soils were significantly higher than that in fluvo-aquic soils, while other metals showed no significant differences among the soil types. Furthermore, Cu, Pb and Zn showed significant concentration decreases with respect to those measured in 2007. The correlation analysis and factor analysis indicated that the contamination of Pb and Cd was mainly caused by economic activities. In addition, the significantly correlated Cu/Ni/Zn and Pb/Cd indicated the inputs from different human activities, while Cr was prone to multiple sources. This study demonstrated that more attention should be given to the contamination by Cr, Pb and Cd, and that the management of human economic activities is vitally imperative for safety of surrounding cropland soils.
Association between Exposure to Air Pollution and Total Gray Matter and Total White Matter Volumes in Adults: A Cross-Sectional Study
Authors: Erickson Lance D. , Gale Shawn D. , Anderson Jacqueline E. , Brown Bruce L. , Hedges Dawson W.
Published: March 2020

Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air pollution—PM2.5, PM2.5–10, PM10, nitrogen dioxide, and nitrogen oxides—and total gray-matter and total white-matter volumes in multivariable regression models in a large sample of adults. We found significant inverse associations between PM2.5 concentration and total white-matter volume and between PM2.5, PM2.5–10, PM10, nitrogen dioxide, and nitrogen oxide concentrations and total gray-matter volume in models adjusted for age, sex, body-mass index, self-assessment of overall health, frequency of alcohol use, smoking status, educational attainment, and income. These findings of pollutant-associated decreases in total gray-matter and total white-matter volumes are in the context of mean PM2.5 concentrations near the upper limit of the World Health Organization’s recommendations. Similarly, mean PM10 concentrations were below the recommended upper limit, and nitrogen dioxide concentration was slightly above. Still, there are many areas in the world with much higher concentrations of these pollutants, which could be associated with larger effects. If replicated, these findings suggest that air pollution could be a risk factor for neurodegeneration.
Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease
Authors: Cavalli Eugenio , Battaglia Giuseppe , Basile Maria Sofia , Bruno Valeria , Petralia Maria Cristina , Lombardo Salvo Danilo , Pennisi Manuela , Kalfin Reni , Tancheva Lyubka , Fagone Paolo , Nicoletti Ferdinando , Mangano Katia
Published: March 2020

Alzheimer’s disease (AD) represents the most common neurodegenerative disorder, with 47 million affected people worldwide. Current treatment strategies are aimed at reducing the symptoms and do slow down the progression of the disease, but inevitably fail in the long-term. Induced pluripotent stem cells (iPSCs)-derived neuronal cells from AD patients have proven to be a reliable model for AD pathogenesis. Here, we have conducted an in silico analysis aimed at identifying pathogenic gene-expression profiles and novel drug candidates. The GSE117589 microarray dataset was used for the identification of Differentially Expressed Genes (DEGs) between iPSC-derived neuronal progenitor (NP) cells and neurons from AD patients and healthy donors. The Discriminant Analysis Module (DAM) algorithm was used for the identification of biomarkers of disease. Drugs with anti-signature gene perturbation profiles were identified using the L1000FWD software. DAM analysis was used to identify a list of potential biomarkers among the DEGs, able to discriminate AD patients from healthy people. Finally, anti-signature perturbation analysis identified potential anti-AD drugs. This study set the basis for the investigation of potential novel pharmacological strategies for AD. Furthermore, a subset of genes for the early diagnosis of AD is proposed.
Characterization of Human NK Cell-Derived Exosomes: Role of DNAM1 Receptor in Exosome-Mediated Cytotoxicity against Tumor
Authors: Di Pace Anna , Tumino Nicola , Besi Francesca , Alicata Claudia , Conti Libenzio , Munari Enrico , Maggi Enrico , Vacca Paola , Moretta Lorenzo
Published: March 2020

Despite the pivotal role of natural killer (NK) cells in defenses against tumors, their exploitation in cancer treatment is still limited due to their reduced ability to reaching tumor sites and the inhibitory effects of tumor microenvironment (TME) on their function. In this study, we have characterized the exosomes from IL2- or IL15-cultured human NK cells. Both cytokines induced comparable amounts of exosomes with similar cargo composition. Analysis of molecules contained within or exposed at the exosome surface, allowed the identification of molecules playing important roles in the NK cell function including IFN-γ, Lymphocyte Function-Associated Antigen (LFA-1), DNAX Accessory Molecule-1 (DNAM1) and Programmed Cell Death Protein (PD-1). Importantly, we show that DNAM1 is involved in exosome-mediated cytotoxicity as revealed by experiments using blocking antibodies to DNAM1 or DNAM1 ligands. In addition, antibody-mediated inhibition of exosome cytotoxicity results in a delay in target cell apoptosis. We also provide evidence that NK-exosomes may exert their cytolytic activity after short time interval and even at low concentrations. Regarding their possible use in immunotherapy, NK exosomes, detectable in peripheral blood, can diffuse into tissues and exert their cytolytic effect at tumor sites. This property offers a clue to integrate cancer treatments with NK exosomes.
Gene Expression Alterations and Molecular Analysis of CHEK1 in Solid Tumors
Authors: Fadaka Adewale Oluwaseun , Bakare Olalekan Olanrewaju , Sibuyi Nicole Remaliah Samantha , Klein Ashwil
Published: March 2020

Alterations in the Checkpoint kinase (CHEK1) gene, its regulation, and the possible clinical outcomes in human solid tumors have not been previously examined. Therefore, the present study was carried out to evaluate the expression of CHEK1 in solid tumors as well as the mechanism by which it can be regulated through non-coding RNAs. The expression of CHEK1 was investigated using Oncomine analysis. cBioPortal, Kaplan–Meier Plotter, and PrognoScan were performed to identify the prognostic roles of this gene in solid tumors. The copy number alteration, mutation, interactive analysis, and visualization of the altered networks were performed by cBioPortal. The molecular binding analysis was carried out by Schrodinger suite, PATCHDOCK, and discovery studio visualizer. The study demonstrated that the CHEK1 gene was differentially expressed in four different cancers, and that reduced CHEK1 mRNA expression is an unfavorable prognostic factor for patients with gastric and colorectal cancer. The molecular docking results showed that the CHEK1 gene can be regulated by microRNAs (miR-195-5p) due to the number of stable hydrogen atoms observed within the distance of 2.0 Å and the favorable amino acids (Ala221, Ile353, Ile365, Ile756, Val797, Val70, Val154, Ile159, Val347, Tyr804, Phe811, Tyr815, and Phe156) identified in the binding pocket of the argonaute protein. Due to the possibility of CHEK1’s involvement in solid tumors, it may potentially be a target for therapeutic intervention in cancer. Further studies into the interaction between CHEK1 and other co-expressed genes may give further insight into other modes of regulation of this gene in cancer patients.
Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells
Authors: Baek Kwang-Hyun , Choi Jihye , Pei Chang-Zhu
Published: March 2020

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.
Rac1 Signaling: From Intestinal Homeostasis to Colorectal Cancer Metastasis
Authors: Kotelevets Larissa , Chastre Eric
Published: March 2020

The small GTPase Rac1 has been implicated in a variety of dynamic cell biological processes, including cell proliferation, cell survival, cell-cell contacts, epithelial mesenchymal transition (EMT), cell motility, and invasiveness. These processes are orchestrated through the fine tuning of Rac1 activity by upstream cell surface receptors and effectors that regulate the cycling Rac1-GDP (off state)/Rac1-GTP (on state), but also through the tuning of Rac1 accumulation, activity, and subcellular localization by post translational modifications or recruitment into molecular scaffolds. Another level of regulation involves Rac1 transcripts stability and splicing. Downstream, Rac1 initiates a series of signaling networks, including regulatory complex of actin cytoskeleton remodeling, activation of protein kinases (PAKs, MAPKs) and transcription factors (NFkB, Wnt/β-catenin/TCF, STAT3, Snail), production of reactive oxygen species (NADPH oxidase holoenzymes, mitochondrial ROS). Thus, this GTPase, its regulators, and effector systems might be involved at different steps of the neoplastic progression from dysplasia to the metastatic cascade. After briefly placing Rac1 and its effector systems in the more general context of intestinal homeostasis and in wound healing after intestinal injury, the present review mainly focuses on the several levels of Rac1 signaling pathway dysregulation in colorectal carcinogenesis, their biological significance, and their clinical impact.
The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism
Authors: Sun Ding-Ping , Lee Yuan-Wen , Chen Jui-Tai , Lin Yung-Wei , Chen Ruei-Ming
Published: March 2020

Glioblastoma multiforme (GBM) is the most common form of brain tumor and is very aggressive. Rapid migration and invasion of glioblastoma cells are two typical features driving malignance of GBM. Bradykinin functionally prompts calcium influx via activation of bradykinin receptor B1/B2 (BDKRB1/2). In this study, we evaluated the roles of bradykinin in migration and invasion of glioblastoma cells and the possible mechanisms. Expressions of aquaporin 4 (AQP4) mRNA and protein were upregulated in human glioblastomas. Furthermore, exposure of human U87 MG glioblastoma cells to bradykinin specifically increased levels of BDKRB1. Successively, bradykinin stimulated influx of calcium, phosphorylation of MEK1 and extracellular signal-regulated kinase (ERK)1/2, translocation and transactivation of nuclear factor-kappaB (NF-κB), and expressions of AQP4 mRNA and protein. Concomitantly, migration and invasion of human glioblastoma cells were elevated by bradykinin. Knocking-down BDKRB1 concurrently decreased AQP4 mRNA expression and cell migration and invasion. The bradykinin-induced effects were further confirmed in murine GL261 glioblastoma cells. Therefore, bradykinin can induce AQP4 expression and subsequent migration and invasion through BDKRB1-mediated calcium influx and subsequent activation of a MEK1-ERK1/2-NF-κB pathway. The bradykinin-BDKRB1 axis and AQP4 could be precise targets for treating GBM patients.
Maximizing the Clinical Benefit of Radiotherapy in Solitary Plasmacytoma: An International Multicenter Analysis
Authors: Elsayad Khaled , Oertel Michael , König Laila , Hüske Sebastian , Le Ray Emmanuelle , Meheissen Mohamed A.M. , Elsaid Amr Abdelaziz , Elfaham Essam , Debus Jürgen , Kirova Youlia , Herfarth Klaus , Eich Hans Theodor
Published: March 2020

Objective: Although local definitive radiotherapy (RT) is considered the standard of care for solitary plasmacytoma (SP), the optimal RT parameters for SP patients have not been defined. The aim of this retrospective study is to analyze the effectiveness of various RT doses, volumes, and techniques, as well as to define the relevant prognostic factors in SP. Methods: Between 2000 and 2019, 84 patients, including 54 with solitary bone plasmacytoma (SBP) and 30 with extramedullary plasmacytoma (EMP), underwent RT at six institutions. Results: The overall RT median dose was 42 Gy (range, 36.0–59.4). The median follow-up period was 46 months. Overall, the local control (LC) rate was 96%, while the complete remission (CR) rate was 46%. The 5-year local relapse-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS), and overall survival (OS) rates were 89%, 71%, 55%, and 93%, respectively. Using an RT dose above 40 Gy was associated with a higher complete remission (CR) rate and a lower rate of local relapse. Modern irradiation techniques were associated with a trend toward a higher LC rate (98% vs. 87% for conventional, p = 0.09) and a significantly lower local relapse rate (6% vs. 25% for conventional, p = 0.04). However, RT dose escalation and technique did not lead to a significant effect on MMFS, PFS, and OS. Univariate analyses identified several patient characteristics as potentially relevant prognostic factors. In SBP patients, systemic therapy administration was associated significantly with MMFS and PFS rates. Conclusion: Using an RT dose >40 Gy and modern RT techniques may improve the local control and reduce the rate of relapse, without a significant impact on survival rates. The addition of systemic therapies may improve the MMFS and PFS rates of SBP patients.
A Subregional Model of System Dynamics Research on Surface Water Resource Assessment for Paddy Rice Production under Climate Change in the Vietnamese Mekong Delta
Authors: Nguyen Thanh Tuu , Tri Van Pham Dang , Kim Seungdo , Nguyen Phuong Thuy , Lam Mong Thuy , Vuong Tuan Phong
Published: March 2020

Effective water management plays an important role in socioeconomic development in the Vietnamese Mekong Delta (VMD). The impacts of climate change and human activities (that is, domestic consumption and industrial and agricultural activities) vary in different subregions of the delta. In order to provide intersectoral data for determining the significantly impacted subregions of the VMD, the present study simulated interactions between local climatic patterns, human activities, and water resources using a system dynamics modeling (SDM) approach with each subregion as an agent of the developed model. The average rainfall and temperature of 121 subregions in the VMD were collected during 1982–2012, and the future changes of climate by provinces were based on the Representative Concentration Pathways (RCP) scenarios (RCP4.5 and RCP8.5) by the end of 21st century. The assessment was based on the levels of impact of various factors, including (1) water consumption, (2) differences between evapotranspiration and rainfall, and (3) spatial distribution of salinity intrusion over the delta scale. In the coastal areas, as well as the central and upstream areas, water resources were projected to be affected by environmental changes, whereas the former, characterized by the lack of surface freshwater, would be affected at a greater scale during the dry season. Besides, the sea level rise would lead to an increase in negative impacts in the eastern coastal areas, suggesting that water-saving techniques should be applied not only for agriculture, but also for industry and domestic water consumption during the dry season. In addition, the south subregions (that is, the western subregions of the Hau River except for An Giang) were likely to be flooded due to the simulated high rainfall and seasonal rises of sea level during the wet season. Therefore, the alternative forms of settlement and livelihood should be considered toward balance management with changing delta dynamics.
High-Performance Semi-Flexible Pavement Coating Material with the Microscopic Interface Optimization
Authors: Xu Yinshan , Jiang Yingjun , Xue Jinshun , Tong Xi , Cheng Yuanyuan
Published: March 2020

This paper aims to optimize the asphalt-mortar interface characteristics of semi-flexible pavement coating material (SFPCM), three types of the interface modifiers, namely the silane coupling agent, carboxylated styrene-butadiene latex, and cationic emulsified asphalt, are selected to add into the cement mortar to optimize the asphalt-mortar interface. The microscopic characteristics of the asphalt-mortar interface and the macroscopic pavement performance of the SFPCM after the interface optimization are investigated to reveal the effect of interface modifiers and determine the best formula. Results show that: (1) The dry shrinkage of the cement mortar is increased with the increased dosage of the interface modifiers, while the strength is decreased accordingly; (2) the optimum dosages of the silane coupling agent, carboxylated styrene butadiene latex, and cationic emulsified asphalt are 0.5%, 10%, and 5%, respectively; (3) the microscopic asphalt-mortar interface characteristics of the SFPCM with different interface modifiers have significant differences; (4) the SFPCM with the cationic emulsified asphalt presents the best pavement performance, particularly the high-temperature stability. These results can be attributed to improve the pavement properties of SFPCM.
USA Wind Energy-Caused Bat Fatalities Increase with Shorter Fatality Search Intervals
Authors: Smallwood K. Shawn
Published: March 2020

Wind turbine collision fatalities of bats have likely increased with the rapid expansion of installed wind energy capacity in the USA since the last national-level fatality estimates were generated in 2012. An assumed linear increase of fatalities with installed capacity would expand my estimate of bat fatalities across the USA from 0.89 million in 2012 to 1.11 million in 2014 and to 1.72 million in 2019. However, this assumed linear relationship could have been invalidated by shifts in turbine size, tower height, fatality search interval during monitoring, and regional variation in bat fatalities. I tested for effects of these factors in fatality monitoring reports through 2014. I found no significant relationship between bat fatality rates and wind turbine size. Bat fatality rates increased with increasing tower height, but this increase mirrored the increase in fatality rates with shortened fatality search intervals that accompanied the increase in tower heights. Regional weighting of mean project-level bat fatalities increased the national-level estimate 17% to 1.3 (95% CI: 0.15–3.0) million. After I restricted the estimate’s basis to project-level fatality rates that were estimated from fatality search intervals <10 days, my estimate increased by another 71% to 2.22 (95% CI: 1.77–2.72) million bat fatalities in the USA’s lower 48 states in 2014. Project-level fatality estimates based on search intervals <10 days were, on average, eight times higher than estimates based on longer search intervals. Shorter search intervals detected more small-bodied species, which contributed to a larger all-bat fatality estimate.
How Creativity in STEAM Modules Intervenes with Self-Efficacy and Motivation
Authors: Conradty Cathérine , Sotiriou Sofoklis A. , Bogner Franz X.
Published: March 2020

Many current curricula, in going beyond traditional goals, increasingly foster creativity in science classrooms, declaring creativity a core skill of the 21st century. For enhancing creativity in science classrooms, the subject Arts is considered to offer a potential way from STEM (Science, Technology, Engineering, Mathematics) to STEAM (STEM with Arts)). The Horizont-2020 project Creations prepared more than 100 creativity-enhancing STEAM modules based on the 5E instructional model. STEM subjects were mathematics, biology, physics, chemistry or technology, and often interdisciplinary for different school and class levels between the ages of nine and nineteen. All modules provided a social environment fostering creativity where students imagine, explore, experiment, test, manipulate, and speculate. Exemplarily, five modules including physics, math, and biology, were selected, for monitoring motivation and creativity. The first was measured on the level of career-motivation and self-efficacy, the latter focused on two sub-constructs: active cognition such as idea processing (Act), and a mental state of creative immersion (Flow). Subjects were a sample of 995 students (9–18 years). In summary, no gender impact or age effect appeared in any of the monitored variables. Participation intervened with Self-Efficacy and Act, while Career Motivation or Flow did not. Act as a cognitive variable associated with creativity might be more sensitive to changes, whereas Flow as a parameter measuring a state of mind related to emotion appears more stable. Path analysis supported the role of creativity for Career-Motivation by promoting Self-Efficacy. Conclusions for appropriate educational settings to foster STEAM environments are discussed.
Dithienylpyrrole Electrografting on a Surface through the Electroreduction of Diazonium Salts
Authors: Le Thi Huong , Nguyen Van Quyen , Trippe-Allard Gaelle , Lacroix Jean-Christophe , Martin Pascal
Published: March 2020

The control of the interface and the adhesion process are key issues for the development of new application based on electrochromic materials. In this work the functionalization of an electrode’s surface through electroreduction of diazonium generated in situ from 4-(2,5-di-thiophen-2-yl-pyrrol-1-yl)-phenylamine (SNS-An) has been proposed. The synthesis of the aniline derivative SNS-An was performed and the electrografting was investigated by cyclic voltammetry on various electrodes. Then the organic thin film was fully characterized by several techniques and XPS analysis confirms the presence of an organic film based on the chemical composition of the starting monomer and allows an estimation of its thickness confirmed by AFM scratching measurements. Depending on the number of electrodeposition cycles, the thickness varies from 2 nm to 10 nm, which corresponds to a few grafted oligomers. In addition, the grafted film showed a good electrochemical stability depending on the scan rates up to 400 V/s and the electrochemical response of the modified electrode towards several redox probes showed that the attached layer acts as a conductive switch. Therefore, the electrode behaves as a barrier to electron transfer when the standard redox potential of the probe is below the layer switching potential, whereas the layer can be considered as transparent towards the electron transfer for redox probes with a redox potential above it.
Lightweight and Seamless Memory Randomization for Mission-Critical Services in a Cloud Platform
Authors: Yun Joobeom , Park Ki-Woong , Koo Dongyoung , Shin Youngjoo
Published: March 2020

Nowadays, various computing services are often hosted on cloud platforms for their availability and cost effectiveness. However, such services are frequently exposed to vulnerabilities. Therefore, many countermeasures have been invented to defend against software hacking. At the same time, more complicated attacking techniques have been created. Among them, code-reuse attacks are still an effective means of abusing software vulnerabilities. Although state-of-the-art address space layout randomization (ASLR) runtime-based solutions provide a robust way to mitigate code-reuse attacks, they have fundamental limitations; for example, the need for system modifications, and the need for recompiling source codes or restarting processes. These limitations are not appropriate for mission-critical services because a seamless operation is very important. In this paper, we propose a novel ASLR technique to provide memory rerandomization without interrupting the process execution. In addition, we describe its implementation and evaluate the results. In summary, our method provides a lightweight and seamless ASLR for critical service applications.
Isolation of Exopolysaccharide-Producing Yeast and Lactic Acid Bacteria from Quinoa (Chenopodium Quinoa) Sourdough Fermentation
Authors: Franco Wendy , Pérez-Díaz Ilenys , Connelly Lauren , Diaz Joscelin
Published: March 2020

Quinoa, a nutritional grain, can be used as an ingredient in gluten-free sourdoughs. This study characterizes quinoa flour spontaneous fermentation with emphasis in the isolation of exopolysaccharide (EPS) producer bacteria. Real, red and black grains were studied. Dough yield, microbiota composition and fermentation biochemistry were determined for a total of 36 quinoa flour fermentations. The fermentation biochemistry was monitored by high-performance liquid chromatography (HPLC) analysis, pH measurement and titratable acidity. Changes in the microbiota were monitored by plating on deMann Rogosa and Sharp 5 agar (MRS5) and yeast and mold agar (YMA) plates and with metagenetic analysis. The ability to produce exopolysaccharides was screened in selected lactic acid bacteria (LAB) isolates. Production of organic acids in the spontaneous fermentation dropped the pH to 4.0 ± 0.3. The community of presumptive LAB reached 8.37 ± 0.01 log colony forming units (CFU)/mL by day 8 of back-slopped fermentations. The microbiota was composed of Lactobacillus, Enterococcus, Leuconostoc, Lactococcus, Pediococcus and Weissella. P. pentosaceous, L. citreum and W. cibaria were able to produce EPS in a starch-rich medium. P. pentosaceous showed higher exopolysaccharide yield, rapid acidifying kinetics and was able to drop the dough broth pH to values below 4.0 and a positive fermentation quotient after 24 h of incubation. Therefore, the bacterium might be a potential candidate for quinoa sourdough production.
Non-Invasive Cerebellar Stimulation in Neurodegenerative Ataxia: A Literature Review
Authors: Benussi Alberto , Pascual-Leone Alvaro , Borroni Barbara
Published: March 2020

Cerebellar ataxias are a heterogenous group of degenerative disorders for which we currently lack effective and disease-modifying interventions. The field of non-invasive brain stimulation has made much progress in the development of specific stimulation protocols to modulate cerebellar excitability and try to restore the physiological activity of the cerebellum in patients with ataxia. In light of limited evidence-based pharmacologic and non-pharmacologic treatment options for patients with ataxia, several different non-invasive brain stimulation protocols have emerged, particularly employing repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) techniques. In this review, we summarize the most relevant rTMS and tDCS therapeutic trials and discuss their implications in the care of patients with degenerative ataxias.
Chondroitin Sulfate Promotes the Proliferation of Keloid Fibroblasts Through Activation of the Integrin and Protein Kinase B Pathways
Authors: Katayama Yasuhiro , Naitoh Motoko , Kubota Hiroshi , Yamawaki Satoko , Aya Rino , Ishiko Toshihiro , Morimoto Naoki
Published: March 2020

Keloids are dermal fibroproliferative tumors that arise beyond the boundary of the original wound edges and invades adjacent tissue. Keloids are characterized by the extensive production of extracellular matrix (ECM) and abnormal fibroblast proliferation. Chondroitin sulfate (CS) is one of the major structural components of cartilage and ECM. Recently, we reported the over-accumulation of CS in keloid lesions. Keloid-derived fibroblasts (KFs) and normal dermal fibroblasts (NFs) were incubated with CS. The fibroblast proliferation rate was analyzed using a tetrazolium salt colorimetric assay. The activation of the intracellular signaling pathway was analyzed by Western blotting. Wortmannin, a PI3K inhibitor, and anti-integrin antibodies were tested to investigate the mechanism of the CS-induced cell proliferation. CS strongly stimulated the proliferation of KFs, but not NFs. The analysis of the intracellular signal transduction pathway revealed that the stimulation effect of CS on KF proliferation was due to the activation of the protein kinase B (AKT) pathway and that integrin α1 was responsible for this phenomenon. We revealed that CS probably activates the AKT pathway through integrin to induce KF proliferation. CS may be a novel clinical therapeutic target in keloids.
Comprehensive Phosphoproteomic Analysis of Pepper Fruit Development Provides Insight into Plant Signaling Transduction
Authors: Liu Zhoubin , Lv Junheng , Liu Yuhua , Wang Jing , Zhang Zhuqing , Chen Wenchao , Song Jingshuang , Yang Bozhi , Tan Fangjun , Zou Xuexiao , Ou Lijun
Published: March 2020

Limited knowledge is available for phosphorylation modifications in pepper (Capsicum annuum L.), especially in pepper fruit development. In this study, we conducted the first comprehensive phosphoproteomic analysis of pepper fruit at four development stage by Tandem Mass Tag proteomic approaches. A total of 2639 unique phosphopeptides spanning 1566 proteins with 4150 nonredundant sites of phosphorylation were identified, among which 2327 peptides in 1413 proteins were accurately quantified at four different stages. Mature Green (MG) to breaker stage showed the largest number of differentially expressed phosphoproteins and the number of downregulated phosphoproteins was significantly higher than that of upregulated after MG stage. Twenty seven phosphorylation motifs, including 22 pSer motifs and five pThr motifs and 85 kinase including 28 serine/threonine kinases, 14 receptor protein kinases, six mitogen-activated protein kinases, seven calcium-dependent protein kinases, two casein kinases, and some other kinases were quantified. Then the dynamic changes of phosphorylated proteins in ethylene and abscisic acid signaling transduction pathways during fruit development were analyzed. Our results provide a cascade of phosphoproteins and a regulatory network of phosphorylation signals, which help to further understand the mechanism of phosphorylation in pepper fruit development.
IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity
Authors: Xu Liang , Shao Yuling , Ren Lin , Liu Xiansheng , Li Yunyun , Xu Jiegou , Ye Yan
Published: March 2020

Previous studies have shown reduced expression of Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) and its tumor-suppressive role in gastric cancer (GC). However, the precise role of SHIP2 in the migration and invasion of GC cells remains unclear. Here, an IQ motif containing the GTPase-activating protein 2 (IQGAP2) as a SHIP2 binding partner, was screened and identified by co-immunoprecipitation and mass spectrometry studies. While IQGAP2 ubiquitously expressed in GC cells, IQGAP2 and SHIP2 co-localized in the cytoplasm of GC cells, and this physical association was confirmed by the binding of IQGAP2 to PRD and SAM domains of SHIP2. The knockdown of either SHIP2 or IQGAP2 promoted cell migration and invasion by inhibiting SHIP2 phosphatase activity, activating Akt and subsequently increasing epithelial–mesenchymal transition (EMT). Furthermore, knockdown of IQGAP2 in SHIP2-overexpressing GC cells reversed the inhibition of cell migration and invasion by SHIP2 induction, which was associated with the suppression of elevated SHIP2 phosphatase activity. Moreover, the deletion of PRD and SAM domains of SHIP2 abrogated the interaction and restored cell migration and invasion. Collectively, these results indicate that IQGAP2 interacts with SHIP2, leading to the increment of SHIP2 phosphatase activity, and thereby inhibiting the migration and invasion of GC cells via the inactivation of Akt and reduction in EMT.
Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates
Authors: Ochoa-Bernal Maria Ariadna , Fazleabas Asgerally T.
Published: March 2020

Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a successful pregnancy. Two of the most critical steps in the establishment of human pregnancy are implantation and decidualization, which are required for maternal interactions with the developing embryo. This review primarily highlights the physiological aspects of these two events and the adverse pregnancy outcomes from defective implantation and decidualization. The focus of this review is to provide a general concept of the mechanisms involved during the window of implantation, description of components involved in the process and possible pathologies that could disrupt the embryo implantation and decidualization and specifically as it applies to women and non-human primates.
The Chironomidae (Diptera) of Svalbard and Jan Mayen
Authors: Stur Elisabeth , Ekrem Torbjørn
Published: March 2020

Non-biting midges of the fly family Chironomidae are extremely abundant and diverse in Arctic regions and are essential components of Arctic ecosystems. Modern identification tools based on documented records of Arctic chironomid species are therefore important for ecological research and environmental monitoring in the region. Here, we provide an updated review of the chironomid fauna of the Svalbard archipelago and the island of Jan Mayen, Norway. Our results show that a total of 73 species distributed across 24 genera in four subfamilies are known from these areas. Our review treats 109 taxa, including nomina dubia and misidentifications. It includes morphological identification keys to all known species as well as photographs of most taxa and DNA barcodes of 66 species. Taxonomic remarks are given for selected taxa, including previous misidentifications and erroneous records. Chironomus islandicus, Tvetenia bavarica, Limnophyes schnelli, Metriocnemus brusti and Metriocnemus fuscipes as well as the genera Allocladius, Corynoneura and Bryophaenocladius are reported from Svalbard for the first time, while Procladius (Holotanypus) frigidus, Stictochironomus psilopterus, Chaetocladius incertus, Orthocladius (Orthocladius) mixtus and Smittia longicosta, previously considered as junior synonyms or nomina dubia, are revived as valid species based on examination of type material or literature. Twenty species within eleven genera are introduced with interim names. Metriocnemus similis is regarded as a junior synonym of Metriocnemus ursinus, and Smittia incerta, Smittia flexinervis and Smittia spitzbergensis are regarded as nomina dubia. Valid taxa no longer considered as part of the Svalbard fauna are Parochlus kiefferi, Arctopelopia barbitarsis, Procladius (Holotanypus) crassinervis, Diamesa lindrothi, Diamesa incallida, Diamesa lundstromi, Chironomus hyperboreus, Sergentia coracina, Camptocladius stercorarius, Chaetocladius dissipatus, Chaetocladius dentiforceps, Chaetocladius laminatus, Chaetocladius perennis, Cricotopus (Cricotopus) humeralis, Cricotopus (Cricotopus) polaris, Hydrosmittia ruttneri, Limnophyes edwardsi, Metriocnemus picipes, Metriocnemus tristellus, Orthocladius (Eudactylocladius) gelidus, Orthocladius (Euorthocladius) thienemanni, Orthocladius (Orthocladius) obumbratus, Orthocladius (Orthocladius) rhyacobius, Paralimnophyes, Paraphaenocladius impensus, Psectrocladius (Monopsectrocladius) calcaratus, Psectrocladius (Psectrocladius) psilopterus, Psectrocladius (Psectrocladius) ventricosus, Smittia lasiophthalma, Smittia lasiops and Zalutschia tatrica.
Jesus Christ’s Speeches in Maria Valtorta’s Mystical Writings: Setting, Topics, Duration and Deep-Language Mathematical Analysis
Authors: Matricciani Emilio , De Caro Liberato
Published: March 2020

We have studied Jesus Christ’s speeches contained in The Gospel as revealed to me by Maria Valtorta to assess: (i) similarities and differences of the speeches delivered to diverse audiences, through deep-language statistics; (ii) duration of the speeches delivered in different occasions; (iii) whether the setting of the speeches is realistic. Mathematically, the speeches can be divided into two sets: (a) two apparently well-planned and coordinated series of speeches delivered at “Clear Water” and at the Horns of Hattin (Sermon of the Mountain); (b) extempore speeches delivered in many localities (parables, speeches to people or to disciples, in Synagogues, at the Temple). By converting sequences of words into intervals, through a suitable reading/speaking speed, the speeches’ durations were found to be realistic. The setting of the speeches allows the assessment of the likelihood of the places and occasions for delivering them. Maria Valtorta wrote extraordinary speeches that she attributed to the alleged Jesus of Nazareth. In addition to their theological and doctrinal contents (whose study is far beyond the scope of this paper), the speeches are so realistic in whatever mathematical parameter, or setting, we study them, that she is either a great literary author, or—as she claims—an attentive “eyewitness” of what she reports.
Assessment of the Psychological Situation in Adults with Congenital Heart Disease
Authors: Andonian Caroline , Beckmann Jürgen , Ewert Peter , Freilinger Sebastian , Kaemmerer Harald , Oberhoffer-Fritz Renate , Sack Martin , Neidenbach Rhoia
Published: March 2020

Background: Due to advances in the diagnosis and treatment of congenital heart disease (CHD), the number of adults who are surviving with congenital heart disease (ACHD) is constantly growing. Until recently, the psychological effects of CHD had been widely neglected. Current research provides evidence for an increased risk of emotional distress in ACHD. The concept of illness identity attempts to explain how patients experience and integrate their CHD into their identities. The present study investigated illness identity in relation to clinical parameters and psychological functioning. Psychometric properties of the German version of the Illness Identity Questionnaire (IIQD) were examined. Methods: Self-reported measures on illness identity and psychological functioning (HADS-D) were assessed in a representative sample of 229 ACHD (38 ± 12.5 (18−73) years; 45% female) at the German Heart Center Munich. Descriptive analyses and multiple regression models were conducted. Confirmatory factor analysis was performed to validate the IIQD. Results: The IIQD demonstrated good reliability. The originally-postulated four-factor structure could not be replicated. Anatomic disease complexity and functional status significantly influenced illness identity. Illness identity accounted for unique variances in depression and anxiety: Maladaptive illness identity states (i.e., , engulfment and rejection) were associated with higher emotional distress, whereas adaptive illness (i.e., , acceptance and enrichment) identity states were linked to lower emotional distress. Conclusions: Illness Identity emerged as a predictor of emotional distress in ACHD. Findings raise the possibility that interventions designed to target a patient’s illness identity may improve psychological well-being and cardiac outcomes in ACHD.