bluuebunny/crossref_metadata_2025 huggingface dataset:
Wee1 Inhibition Enhances the Anti-Tumor Effects of Capecitabine in Preclinical Models of Triple-Negative Breast Cancer
Authors: Pitts Todd M. , Simmons Dennis M. , Bagby Stacey M. , Hartman Sarah J. , Yacob Betelehem W. , Gittleman Brian , Tentler John J. , Cittelly Diana , Ormond D. Ryan , Messersmith Wells A. , Eckhardt S. Gail , Diamond Jennifer R.
Published: March 2020

Triple-negative breast cancer (TNBC) is an aggressive subtype defined by lack of hormone receptor expression and non-amplified HER2. Adavosertib (AZD1775) is a potent, small-molecule, ATP-competitive inhibitor of the Wee1 kinase that potentiates the activity of many DNA-damaging chemotherapeutics and is currently in clinical development for multiple indications. The purpose of this study was to investigate the combination of AZD1775 and capecitabine/5FU in preclinical TNBC models. TNBC cell lines were treated with AZD1775 and 5FU and cellular proliferation was assessed in real-time using IncuCyte® Live Cell Analysis. Apoptosis was assessed via the Caspase-Glo 3/7 assay system. Western blotting was used to assess changes in expression of downstream effectors. TNBC patient-derived xenograft (PDX) models were treated with AZD1775, capecitabine, or the combination and assessed for tumor growth inhibition. From the initial PDX screen, two of the four TNBC PDX models demonstrated a better response in the combination treatment than either of the single agents. As confirmation, two PDX models were expanded for statistical comparison. Both PDX models demonstrated a significant growth inhibition in the combination versus either of the single agents. (TNBC012, p < 0.05 combo vs. adavosertib or capecitabine, TNBC013, p < 0.01 combo vs. adavosertib or capecitabine.) An enhanced anti-proliferative effect was observed in the adavosertib/5FU combination treatment as measured by live cell analysis. An increase in apoptosis was observed in two of the four cell lines in the combination when compared to single-agent treatment. Treatment with adavosertib as a single agent resulted in a decrease in p-CDC2 in a dose-dependent manner that was also observed in the combination treatment. An increase in γH2AX in two of the four cell lines tested was also observed. No significant changes were observed in Bcl-xL following treatment in any of the cell lines. The combination of adavosertib and capecitabine/5FU demonstrated enhanced combination effects both in vitro and in vivo in preclinical models of TNBC. These results support the clinical investigation of this combination in patients with TNBC, including those with brain metastasis given the CNS penetration of both agents.
Sea Hare Hydrolysate-Induced Reduction of Human Non-Small Cell Lung Cancer Cell Growth through Regulation of Macrophage Polarization and Non-Apoptotic Regulated Cell Death Pathways
Authors: Nyiramana Marie Merci , Cho Soo Buem , Kim Eun-Jin , Kim Min Jun , Ryu Ji Hyeon , Nam Hyun Jae , Kim Nam-Gil , Park Si-Hyang , Choi Yeung Joon , Kang Sang Soo , Jung Myunghwan , Shin Min-Kyoung , Han Jaehee , Jang In-Seok , Kang Dawon
Published: March 2020

Sea hare-derived compounds induce macrophage activation and reduce asthmatic parameters in mouse models of allergic asthma. These findings led us to study the role of sea hare hydrolysates (SHH) in cancer pathophysiology. SHH treatment-induced M1 macrophage activation in RAW264.7 cells, peritoneal macrophages, and THP-1 cells, as did lipopolysaccharide (LPS) (+ INF-γ), whereas SHH reduced interleukin (IL)-4 (+IL-13)-induced M2 macrophage polarization. In addition, SHH treatment inhibited the actions of M1 and M2 macrophages, which have anticancer and pro-cancer effects, respectively, in non-small cell lung cancer cells (A549 and HCC-366) and tumor-associated macrophages (TAMs). Furthermore, SHH induced G2/M phase arrest and cell death in A549 cells. SHH also downregulated STAT3 activation in macrophages and A549 cells, and the down-regulation was recovered by colivelin, a STAT3 activator. SHH-induced reduction of M2 polarization and tumor growth was blocked by colivelin treatment. SHH-induced cell death did not occur in the manner of apoptotic signaling pathways, while the death pattern was mediated through pyroptosis/necroptosis, which causes membrane rupture, formation of vacuoles and bleb, activation of caspase-1, and secretion of IL-1β in SHH-treated A549 cells. However, a combination of SHH and colivelin blocked caspase-1 activation. Z-YVAD-FMK and necrostatin-1, pyrotosis and necroptosis inhibitors, attenuated SHH’s effect on the cell viability of A549 cells. Taken together, SHH showed anticancer effects through a cytotoxic effect on A549 cells and a regulatory effect on macrophages in A549 cells. In addition, the SHH-induced anticancer effects were mediated by non-apoptotic regulated cell death pathways under STAT3 inhibition. These results suggest that SHH may be offered as a potential remedy for cancer immunotherapy.
Catalysis for Global Development. Contributions around the Iberoamerican Federation of Catalysis
Authors: Gomes Helder , Faria Joaquim
Published: March 2020

Following biennial meetings held since 1968, the Iberoamerican Federation of Catalysis Societies (FISoCat), the Portuguese Chemical Society (SPQ) and the University of Coimbra jointly organized the XXVI Iberoamerican Congress on Catalysis (CICat 2018), which took place in the historic city of Coimbra, Portugal, between the 9th and 14th of September 2018 [...]
The Transcription Factor Nfix Requires RhoA-ROCK1 Dependent Phagocytosis to Mediate Macrophage Skewing during Skeletal Muscle Regeneration
Authors: Saclier Marielle , Lapi Michela , Bonfanti Chiara , Rossi Giuliana , Antonini Stefania , Messina Graziella
Published: March 2020

Macrophages (MPs) are immune cells which are crucial for tissue repair. In skeletal muscle regeneration, pro-inflammatory cells first infiltrate to promote myogenic cell proliferation, then they switch into an anti-inflammatory phenotype to sustain myogenic cells differentiation and myofiber formation. This phenotypical switch is induced by dead cell phagocytosis. We previously demonstrated that the transcription factor Nfix, a member of the nuclear factor I (Nfi) family, plays a pivotal role during muscle development, regeneration and in the progression of muscular dystrophies. Here, we show that Nfix is mainly expressed by anti-inflammatory macrophages. Upon acute injury, mice deleted for Nfix in myeloid line displayed a significant defect in the process of muscle regeneration. Indeed, Nfix is involved in the macrophage phenotypical switch and macrophages lacking Nfix failed to adopt an anti-inflammatory phenotype and interact with myogenic cells. Moreover, we demonstrated that phagocytosis induced by the inhibition of the RhoA-ROCK1 pathway leads to Nfix expression and, consequently, to acquisition of the anti-inflammatory phenotype. Our study identified Nfix as a link between RhoA-ROCK1-dependent phagocytosis and the MP phenotypical switch, thus establishing a new role for Nfix in macrophage biology for the resolution of inflammation and tissue repair.
Scalable Generation of Mesenchymal Stem Cells and Adipocytes from Human Pluripotent Stem Cells
Authors: Karam Manale , Younis Ihab , Elareer Noor R. , Nasser Sara , Abdelalim Essam M.
Published: March 2020

Human pluripotent stem cells (hPSCs) can provide unlimited supply for mesenchymal stem cells (MSCs) and adipocytes that can be used for therapeutic applications. Here we developed a simple and highly efficient all-trans-retinoic acid (RA)-based method for generating an off-the-shelf and scalable number of human pluripotent stem cell (hPSC)-derived MSCs with enhanced adipogenic potential. We showed that short exposure of multiple hPSC lines (hESCs/hiPSCs) to 10 μM RA dramatically enhances embryoid body (EB) formation through regulation of genes activating signaling pathways associated with cell proliferation, survival and adhesion, among others. Disruption of cell adhesion induced the subsequent differentiation of the highly expanded RA-derived EB-forming cells into a pure population of multipotent MSCs (up to 1542-fold increase in comparison to RA-untreated counterparts). Interestingly, the RA-derived MSCs displayed enhanced differentiation potential into adipocytes. Thus, these findings present a novel RA-based approach for providing an unlimited source of MSCs and adipocytes that can be used for regenerative medicine, drug screening and disease modeling applications.
The Significance of the Dysregulation of Canonical Wnt Signaling in Head and Neck Squamous Cell Carcinomas
Authors: Paluszczak Jarosław
Published: March 2020

The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.
Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose
Authors: Velásquez Sonia Y. , Himmelhan Bianca S. , Kassner Nina , Coulibaly Anna , Schulte Jutta , Brohm Kathrin , Lindner Holger A.
Published: March 2020

Natural killer (NK) cells are among the first innate immune cells to arrive at sites of tissue inflammation and regulate the immune response to infection and tumors by the release of cytokines including interferon (IFN)γ. In vitro exposure to the innate cytokines interleukin 15 (IL-15) and IL-12/IL-18 enhances NK cell IFNγ production which, beyond 16 h of culture, was shown to depend on metabolic switching to glycolysis. NK effector responses are, however, rapid by comparison. Therefore, we sought to evaluate the importance of glycolysis for shorter-term IFNγ production, considering glucose deprivation and hypoxia as adverse tissue inflammation associated conditions. Treatments with IL-15 for 6 and 16 h were equally effective in priming early IFNγ production in human NK cells in response to secondary IL-12/IL-18 stimulation. Short-term priming was not associated with glycolytic switching but induced the release of IFNγ and, additionally, CCL3, CCL4 and CCL5 from both normoxic and hypoxic NK cells in an equally efficient and, unexpectedly, glucose independent manner. We conclude that release of IFNγ and CC chemokines in the early innate immune response is a metabolically autonomous NK effector program.
Gut–Liver Axis and Inflammasome Activation in Cholangiocyte Pathophysiology
Authors: Maroni Luca , Ninfole Elisabetta , Pinto Claudio , Benedetti Antonio , Marzioni Marco
Published: March 2020

The Nlrp3 inflammasome is a multiprotein complex activated by a number of bacterial products or danger signals and is involved in the regulation of inflammatory processes through caspase-1 activation. The Nlrp3 is expressed in immune cells but also in hepatocytes and cholangiocytes, where it appears to be involved in regulation of biliary damage, epithelial barrier integrity and development of fibrosis. Activation of the pathways of innate immunity is crucial in the pathophysiology of hepatobiliary diseases, given the strong link between the gut and the liver. The liver secretes bile acids, which influence the bacterial composition of the gut microbiota and, in turn, are heavily modified by microbial metabolism. Alterations of this balance, as for the development of dysbiosis, may deeply influence the composition of the bacterial products that reach the liver and are able to activate a number of intracellular pathways. This alteration may be particularly important in the pathogenesis of cholangiopathies and, in particular, of primary sclerosing cholangitis, given its strong association with inflammatory bowel disease. In the present review, we summarize current knowledge on the gut–liver axis in cholangiopathies and discuss the role of Nlrp3 inflammasome activation in cholestatic conditions.
Function of Torsin AAA+ ATPases in Pseudorabies Virus Nuclear Egress
Authors: Hölper Julia E. , Klupp Barbara G. , Luxton G. W. Gant , Franzke Kati , Mettenleiter Thomas C.
Published: March 2020

Newly assembled herpesvirus nucleocapsids traverse the intact nuclear envelope by a vesicle-mediated nucleo-cytoplasmic transport for final virion maturation in the cytoplasm. For this, they bud at the inner nuclear membrane resulting in primary enveloped particles in the perinuclear space (PNS) followed by fusion of the primary envelope with the outer nuclear membrane (ONM). While the conserved viral nuclear egress complex orchestrates the first steps, effectors of fusion of the primary virion envelope with the ONM are still mostly enigmatic but might include cellular proteins like SUN2 or ESCRT-III components. Here, we analyzed the influence of the only known AAA+ ATPases located in the endoplasmic reticulum and the PNS, the Torsins (Tor), on nuclear egress of the alphaherpesvirus pseudorabies virus. For this overexpression of wild type and mutant proteins as well as CRISPR/Cas9 genome editing was applied. Neither single overexpression nor gene knockout (KO) of TorA or TorB had a significant impact. However, TorA/B double KO cells showed decreased viral titers at early time points of infection and an accumulation of primary virions in the PNS pointing to a delay in capsid release during nuclear egress.
Insulin Resistance Promotes Parkinson’s Disease through Aberrant Expression of α-Synuclein, Mitochondrial Dysfunction, and Deregulation of the Polo-Like Kinase 2 Signaling
Authors: Hong Chien-Tai , Chen Kai-Yun , Wang Weu , Chiu Jing-Yuan , Wu Dean , Chao Tsu-Yi , Hu Chaur-Jong , Chau Kai-Yin , Bamodu Oluwaseun
Published: March 2020

Background: Insulin resistance (IR), considered a hallmark of diabetes at the cellular level, is implicated in pre-diabetes, results in type 2 diabetes, and negatively affects mitochondrial function. Diabetes is increasingly associated with enhanced risk of developing Parkinson’s disease (PD); however, the underlying mechanism remains unclear. This study investigated the probable culpability of IR in the pathogenesis of PD. Methods: Using MitoPark mice in vivo models, diabetes was induced by a high-fat diet in the in vivo models, and IR was induced by protracted pulse-stimulation with 100 nM insulin treatment of neuronal cells, in vitro to determine the molecular mechanism(s) underlying altered cellular functions in PD, including mitochondrial dysfunction and α-synuclein (SNCA) aberrant expression. Findings: We observed increased SNCA expression in the dopaminergic (DA) neurons of both the wild-type and diabetic MitoPark mice, coupled with enhanced degeneration of DA neurons in the diabetic MitoPark mice. Ex vivo, in differentiated human DA neurons, IR was associated with increased SNCA and reactive oxygen species (ROS) levels, as well as mitochondrial depolarization. Moreover, we demonstrated concomitant hyperactivation of polo-like kinase-2 (PLK2), and upregulated p-SNCA (Ser129) and proteinase K-resistant SNCA proteins level in IR SH-SY5Y cells, however the inhibition of PLK2 reversed IR-related increases in phosphorylated and total SNCA. Similarly, the overexpression of peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC)-1α suppressed ROS production, repressed PLK2 hyperactivity, and resulted in downregulation of total and Ser129-phosphorylated SNCA in the IR SH-SY5Y cells. Conclusions: These findings demonstrate that IR-associated diabetes promotes the development and progression of PD through PLK2-mediated mitochondrial dysfunction, upregulated ROS production, and enhanced SNCA signaling, suggesting the therapeutic targetability of PLK2 and/or SNCA as potential novel disease-modifying strategies in patients with PD.
O-acetylated Gangliosides as Targets for Cancer Immunotherapy
Authors: Cavdarli Sumeyye , Delannoy Philippe , Groux-Degroote Sophie
Published: March 2020

O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until now. O-acetylated ganglioside species are mainly expressed during embryonic development and in the central nervous system in healthy adults, but are re-expressed during cancer development and are considered as markers of cancers of neuroectodermal origin. However, the specific biological roles of O-acetylated gangliosides in developing and malignant tissues have not been extensively studied, mostly because of the requirement of specific approaches and tools for sample preparation and analysis. In this review, we summarize our current knowledge of ganglioside biosynthesis and expression in normal and pathological conditions, of ganglioside O-acetylation analysis and expression in cancers, and of the possible use of O-acetylated gangliosides as targets for cancer immunotherapy.
A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells
Authors: Deiana Michela , Dalle Carbonare Luca , Serena Michela , Cheri Samuele , Mutascio Simona , Gandini Alberto , Innamorati Giulio , Lorenzi Pamela , Cumerlato Michela , Bertacco Jessica , Antoniazzi Franco , Romanelli Maria Grazia , Mottes Monica , Zipeto Donato , Valenti Maria Teresa
Published: March 2020

Ectopic expression of RUNX2 has been reported in several tumors. In melanoma cells, the RUNT domain of RUNX2 increases cell proliferation and migration. Due to the strong link between RUNX2 and skeletal development, we hypothesized that the RUNT domain may be involved in the modulation of mechanisms associated with melanoma bone metastasis. Therefore, we evaluated the expression of metastatic targets in wild type (WT) and RUNT KO melanoma cells by array and real-time PCR analyses. Western blot, ELISA, immunofluorescence, migration and invasion ability assays were also performed. Our findings showed that the expression levels of bone sialoprotein (BSP) and osteopontin (SPP1) genes, which are involved in malignancy-induced hypercalcemia, were reduced in RUNT KO cells. In addition, released PTHrP levels were lower in RUNT KO cells than in WT cells. The RUNT domain also contributes to increased osteotropism and bone invasion in melanoma cells. Importantly, we found that the ERK/p-ERK and AKT/p-AKT pathways are involved in RUNT-promoted bone metastases. On the basis of our findings, we concluded that the RUNX2 RUNT domain is involved in the mechanisms promoting bone metastasis of melanoma cells via complex interactions between multiple players involved in bone remodeling.
Understanding the Synergy of NKp46 and Co-Activating Signals in Various NK Cell Subpopulations: Paving the Way for More Successful NK-Cell-Based Immunotherapy
Authors: Zamai Loris , Del Zotto Genny , Buccella Flavia , Gabrielli Sara , Canonico Barbara , Artico Marco , Ortolani Claudio , Papa Stefano
Published: March 2020

The NK cell population is characterized by distinct NK cell subsets that respond differently to the various activating stimuli. For this reason, the determination of the optimal cytotoxic activation of the different NK cell subsets can be a crucial aspect to be exploited to counter cancer cells in oncologic patients. To evaluate how the triggering of different combination of activating receptors can affect the cytotoxic responses of different NK cell subsets, we developed a microbead-based degranulation assay. By using this new assay, we were able to detect CD107a+ degranulating NK cells even within the less cytotoxic subsets (i.e., resting CD56bright and unlicensed CD56dim NK cells), thus demonstrating its high sensitivity. Interestingly, signals delivered by the co-engagement of NKp46 with 2B4, but not with CD2 or DNAM-1, strongly cooperate to enhance degranulation on both licensed and unlicensed CD56dim NK cells. Of note, 2B4 is known to bind CD48 hematopoietic antigen, therefore this observation may provide the rationale why CD56dim subset expansion correlates with successful hematopoietic stem cell transplantation mediated by alloreactive NK cells against host T, DC and leukemic cells, while sparing host non-hematopoietic tissues and graft versus host disease. The assay further confirms that activation of LFA-1 on NK cells leads to their granule polarization, even if, in some cases, this also takes to an inhibition of NK cell degranulation, suggesting that LFA-1 engagement by ICAMs on target cells may differently affect NK cell response. Finally, we observed that NK cells undergo a time-dependent spontaneous (cytokine-independent) activation after blood withdrawal, an aspect that may strongly bias the evaluation of the resting NK cell response. Altogether our data may pave the way to develop new NK cell activation and expansion strategies that target the highly cytotoxic CD56dim NK cells and can be feasible and useful for cancer and viral infection treatment.
Acceptability and Societal Impact of the Introduction of Bioplastics as Novel Environmentally Friendly Packaging Materials in Ireland
Authors: Neves Adriana C. , Moyne Martina M. , Eyre Colin , Casey Brian P.
Published: March 2020

Novel environmentally friendly alternatives for packaging materials such as bioplastics are being developed to mitigate problems with petrochemical plastics but low acceptance of these bioplastics among consumers and others have delayed their adoption. Through a mixed method approach, this work aims to assess the factors contributing to the low adoption rates of bioplastics as a way to inform development of more highly accepted bioplastics. Stakeholders with a variety of links with the packaging/plastic industries were interviewed using a semi-structured interview approach and the results were analysed to discover recurrent themes and perceptions regarding packaging. From this thematic analysis, a survey was conducted to explore consumer opinion. The findings indicate that although the population is aware and interested in changing to environmentally friendly packaging, confusion exists as to what that means and what are the best ways to effect that change. The teenager group was identified as the most susceptible to be involved in the change. Frequently cited barriers to acceptance centred on separation of waste and access to correct waste bins. The characteristics likely to lead to a higher acceptance of novel bioplastics by composters were time of decomposition, small thickness, and possibility of being introduced in current processes of packaging preparation, among others.
Development of Polylactic Acid Films with Selenium Microparticles and Its Application for Food Packaging
Authors: Lu Rui , Sameen Dur E. , Qin Wen , Wu Dingtao , Dai Jianwu , Li Suqing , Liu Yaowen
Published: March 2020

Selenium is a natural element which exists in the human body and plays an important role in metabolism. Along with this, selenium also possesses antibacterial and antioxidant properties. Using selenium microparticles (SeMPs) in food packaging films is exceptional. In this experiment, a solution casting method was used to make film. For this purpose, we used polylactic acid (PLA) as a substrate for the formation of a film membrane while SeMPs were added with certain ratios to attain antibacterial and antioxidant properties. The effects of SeMPs on the PLA film and the value of SeMPs in food packaging film production were investigated. The effects of the SeMPs contents on the features of the film, such as its mechanical property, solubility, swelling capacity, water vapor permeability, antioxidant activity, and the antibacterial activity of the composite membrane against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) strains, were studied. The results manifest that the PLA/SeMPs films showed higher water resistance, UV resistance, antioxidant activity, and antibacterial activity than pure PLA film. When the concentration of SeMPs was 1.5 wt%, the composite membrane showed the best comprehensive performance. Although the tensile strength and elongation at break of the membrane were slightly reduced by the addition of SeMPs, the results show that PLA/SeMPs films are still suitable for food packaging and would be a very promising material for food packaging.
Insight into the Release Agents/PVD Coatings Interaction for Plastic Mold Technology
Authors: D’Avico Luigi , Beltrami Ruben , Pargoletti Eleonora , Trasatti Stefano P.M. , Cappelletti Giuseppe
Published: March 2020

In polymer processing, the formation of undesired fouling hinders the plastic manufacturing processes. Hence, the use of emulsions as releasing agents is mandatory and their affinity to the mold substrates plays a crucial role. Therefore, this research work has been focused on the wetting properties of commercial water-based release agents (namely Marbocote® W2140, EP, EV-333) towards different Physical Vapor Deposition (PVD) nitride coatings (AlTiN, NbN, ZrN and TiN), usually adopted in the industrial manufacture of Hydrogenated Nitrile Butadiene Rubber (HNBR). The investigated solid substrates were characterized by means of profilometry, SEM/EDX and Surface Free Energy (SFE) analyses, whereas, tensiometric determinations were acquired on the commercial pure and diluted emulsions. The release agents/mold substrates wettability features were studied by means of the work of adhesion and the spreading coefficient. Finally, nitride-coated mold seals were directly tested in an industrial plant with the most performing release agent in terms of adhesive features; for the first time, a deep correlation between the service life, in terms of number of molded seals, and surface (contact angles, work of adhesion and spreading coefficient)/electrochemical (OCP) features was drawn.
Zirconium-Aluminum-Oxide Dielectric Layer with High Dielectric and Relatively Low Leakage Prepared by Spin-Coating and the Application in Thin-Film Transistor
Authors: Liang Zhihao , Zhou Shangxiong , Cai Wei , Fu Xiao , Ning Honglong , Chen Junlong , Yuan Weijian , Zhu Zhennan , Yao Rihui , Peng Junbiao
Published: March 2020

In this paper, zirconium–aluminum–oxide (ZAO) dielectric layers were prepared by a solution method with intent to combine the high dielectric constant with a low leakage current density. As a result, dielectric layers with improved electrical properties as expected can be obtained by spin-coating the mixed precursor. The chemical and physical properties of the films were measured by thermogravimetric differential scanning calorimetry (TG-DSC), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and a UV spectrometer. It is observed that the oxygen defects and the hydroxide in the films are reduced with the addition of high-bond-energy zirconia, while the films can remain large optical bond gaps thanks to the presence of alumina. The metal-insulator-metal (MIM) devices were fabricated, and it was seen that with a molar ratio of Zr:Al = 3:1 and an annealing temperature of 500 °C, the dielectric layer afforded the highest dielectric constant of 21.1, as well as a relatively low leakage current of 2.5 10−6 A/cm2@1MV/cm. Furthermore, the indium–gallium–zinc oxide thin-film transistors (IGZO-TFTs) with an optimal ZAO dielectric layer were prepared by the solution method and a mobility of 14.89 cm2/Vs, and a threshold voltage swing of 0.11 V/dec and a 6.1 106 on/off ratio were achieved at an annealing temperature of 500 °C.
Simulation-Based EDAs for Stochastic Programming Problems
Authors: Hedar Abdel-Rahman , Allam Amira , Abdel-Hakim Alaa
Published: March 2020

With the rapid growth of simulation software packages, generating practical tools for simulation-based optimization has attracted a lot of interest over the last decades. In this paper, a modified method of Estimation of Distribution Algorithms (EDAs) is constructed by a combination with variable-sample techniques to deal with simulation-based optimization problems. Moreover, a new variable-sample technique is introduced to support the search process whenever the sample sizes are small, especially in the beginning of the search process. The proposed method shows efficient results by simulating several numerical experiments.
Ultrasound Assessment of the Abdominal Wall Muscles in Women with and without Primary Dysmenorrhea: A Cross-Sectional Study
Authors: Romero-Morales Carlos , de la Cueva-Reguera Mónica , Miñambres-Vallejo Beatriz , Ruiz-Ruiz Beatriz , Calvo-Lobo César , Casado-Hernández Israel , López-López Daniel , Abuín-Porras Vanesa
Published: March 2020

Background: Primary dysmenorrhea (PD) is one of the most common gynecological disorders in women of reproductive age that may affect quality of life. It is believed that the underlying cause of PD may be the excessive production of prostaglandins (PGs), however, between 20%–25% of women with PD did not respond to pharmacological treatments, showing that nociceptive mechanisms underlying PD are still not understood. The purpose of this study was to measure and compare, through the use of ultrasound imaging, the thickness at rest of the abdominal wall, as well as the interrecti distance (IRD), in women with and without PD. Methods: A cross-sectional study has been performed using ultrasound imaging (USI) to measure the resting thickness of the external oblique (EO), internal oblique (IO), transversus abdominis (TrAb), rectus abdominis (RA), as well as the IRD in a sample of 39 women, 19 with PD and 20 without PD (median ± IR age: 20 ± 4 and 22.5 ± 7 years, respectively). Results: Findings of muscular thickness did not reveal statically significant differences (p < 0.05) in EO, IO, TrAb, RA, and the IRD between the PD group and control group. Conclusions: These findings suggest that the thickness of the abdominal wall is not associated with PD.
Factors Related to Cardiac Troponin T Increase after Participation in a 100 Km Ultra-Marathon
Authors: Małek Łukasz A. , Czajkowska Anna , Mróz Anna , Witek Katarzyna , Nowicki Dariusz , Postuła Marek
Published: March 2020

Background: Intensive and prolonged exercise leads to a rise of troponin concentration in blood. The mechanism responsible for troponin release during exercise remains ill-defined. The study aim was to search for risk factors of troponin increase after a prolonged endurance competition. Methods: The study included a group of 18 amateurs, healthy volunteers (median age 41.5 years, interquartile range – IQR 36–53 years, 83% male) who participated in a 100 km running ultra-marathon. Information on demographic characteristics, pre- and post-race heart rate, blood pressure, body composition and glucose, lactate (L), troponin T (hs-TnT) and C reactive protein (hs-CRP) concentration were obtained. Additionally, data on L and glucose levels every 9.2 km and fluid/food intakes during the race were collected. Results: There was a significant hs-TnT increase after the race exceeding upper reference values in 66% of runners (from 5 IQR 3–7 ng/L to 14 IQR 12–26 ng/L, p < 0.0001). None of the baseline parameters predicted a post-race hs-TnT increase. The only factors, correlating with changes of hs-TnT were mean L concentration during the race (rho = 0.52, p = 0.03) and change of hs-CRP concentration (rho = 0.59, p = 0.01). Conclusions: Participation in a 100 km ultra-marathon leads to a modest, but significant hs-TnT increase in the majority of runners. Among analysed parameters only mean lactate concentration during the race and change in hs-CRP correlated with troponin change.
Invariant-Based Inverse Engineering for Fast and Robust Load Transport in a Double Pendulum Bridge Crane
Authors: Lizuain Ion , Tobalina Ander , Rodriguez-Prieto Alvaro , Muga Juan Gonzalo
Published: March 2020

We set a shortcut-to-adiabaticity strategy to design the trolley motion in a double-pendulum bridge crane. The trajectories found guarantee payload transport without residual excitation regardless of the initial conditions within the small oscillations regime. The results are compared with exact dynamics to set the working domain of the approach. The method is free from instabilities due to boundary effects or to resonances with the two natural frequencies.
Stability Analysis of the Explicit Difference Scheme for Richards Equation
Authors: Liu Fengnan , Fukumoto Yasuhide , Zhao Xiaopeng
Published: March 2020

A stable explicit difference scheme, which is based on forward Euler format, is proposed for the Richards equation. To avoid the degeneracy of the Richards equation, we add a perturbation to the functional coefficient of the parabolic term. In addition, we introduce an extra term in the difference scheme which is used to relax the time step restriction for improving the stability condition. With the augmented terms, we prove the stability using the induction method. Numerical experiments show the validity and the accuracy of the scheme, along with its efficiency.
Gaussian Curvature Entropy for Curved Surface Shape Generation
Authors: Okano Akihiro , Matsumoto Taishi , Kato Takeo
Published: March 2020

The overall shape features that emerge from combinations of shape elements, such as “complexity” and “order”, are important in designing shapes of industrial products. However, controlling the features of shapes is difficult and depends on the experience and intuition of designers. Among these features, “complexity” is said to have an influence on the “beauty” and “preference” of shapes. This research proposed a Gaussian curvature entropy as a “complexity” index of a curved surface shape. The proposed index is calculated based on Gaussian curvature, which is obtained by the sampling and quantization of a curved surface shape and validated by the sensory evaluation experiment while using two types of sample shapes. The result indicates the correspondence of the index to perceived “complexity” (the determination coefficient is greater than 0.8). Additionally, this research constructed a shape generation method that was based on the index as a car design supporting apparatus, in which the designers can refer many shapes generated by controlling “complexity”. The applicability of the proposed method was confirmed by the experiment while using the generated shapes.
Improved Practical Vulnerability Analysis of Mouse Data According to Offensive Security based on Machine Learning in Image-Based User Authentication
Authors: Lee Kyungroul , Lee Sun-Young
Published: March 2020

The objective of this study was to verify the feasibility of mouse data exposure by deriving features to improve the accuracy of a mouse data attack technique using machine learning models. To improve the accuracy, the feature appearing between the mouse coordinates input from the user was analyzed, which is defined as a feature for machine learning models to derive a method of improving the accuracy. As a result, we found a feature where the distance between the coordinates is concentrated in a specific range. We verified that the mouse data is apt to being stolen more accurately when the distance is used as a feature. An accuracy of over 99% was achieved, which means that the proposed method almost completely classifies the mouse data input from the user and the mouse data generated by the defender.
Impact of General Anesthesia Guided by State Entropy (SE) and Response Entropy (RE) on Perioperative Stability in Elective Laparoscopic Cholecystectomy Patients—A Prospective Observational Randomized Monocentric Study
Authors: Dinu Anca Raluca , Rogobete Alexandru Florin , Popovici Sonia Elena , Bedreag Ovidiu Horea , Papurica Marius , Dumbuleu Corina Maria , Velovan Raluca Ramona , Toma Daiana , Georgescu Corina Maria , Trache Lavinia Ioana , Barsac Claudiu , Luca Loredana , Buzzi Bettina , Maghiar Andra , Sandesc Mihai Alexandru , Rimawi Samir , Vaduva Madalin Marian , Bratu Lavinia Melania , Luminosu Paul Manuel , Sandesc Dorel
Published: March 2020

Laparoscopic cholecystectomy is one of the most frequently performed interventions in general surgery departments. Some of the most important aims in achieving perioperative stability in these patients is diminishing the impact of general anesthesia on the hemodynamic stability and the optimization of anesthetic drug doses based on the individual clinical profile of each patient. The objective of this study is the evaluation of the impact, as monitored through entropy (both state entropy (SE) and response entropy (RE)), that the depth of anesthesia has on the hemodynamic stability, as well as the doses of volatile anesthetic. A prospective, observational, randomized, and monocentric study was carried out between January and December 2019 in the Clinic of Anesthesia and Intensive Care of the “Pius Brînzeu” Emergency County Hospital in Timișoara, Romania. The patients included in the study were divided in two study groups: patients in Group A (target group) received multimodal monitoring, which included monitoring of standard parameters and of entropy (SE and RE); while the patients in Group B (control group) only received standard monitoring. The anesthetic dose in group A was optimized to achieve a target entropy of 40–60. A total of 68 patients met the inclusion criteria and were allocated to one of the two study groups: group A (N = 43) or group B (N = 25). There were no statistically significant differences identified between the two groups for both demographical and clinical characteristics (p > 0.05). Statistically significant differences were identified for the number of hypotensive episodes (p = 0.011, 95% CI: [0.1851, 0.7042]) and for the number of episodes of bradycardia (p < 0.0001, 95% CI: [0.3296, 0.7923]). Moreover, there was a significant difference in the Sevoflurane consumption between the two study groups (p = 0.0498, 95% CI: [−0.3942, 0.9047]). The implementation of the multimodal monitoring protocol, including the standard parameters and the measurement of entropy for determining the depth of anesthesia (SE and RE) led to a considerable improvement in perioperative hemodynamic stability. Furthermore, optimizing the doses of anesthetic drugs based on the individual clinical profile of each patient led to a considerable decrease in drug consumption, as well as to a lower incidence of hemodynamic side-effects.
Digital Learning Environments in Higher Education: A Literature Review of the Role of Individual vs. Social Settings for Measuring Learning Outcomes
Authors: Kümmel Elke , Moskaliuk Johannes , Cress Ulrike , Kimmerle Joachim
Published: March 2020

Research on digital learning environments has traditionally applied either an individual perspective or a social perspective to learning. Based on a literature review, we examined to what extent individual or social perspectives determined the learning outcome variables that researchers have used as measurements in existing studies. We analyzed prototypical approaches to operationalize learning settings (individual vs. social) published in peer-reviewed journals and identified their relation to several measures of learning outcomes. We rated n = 356 articles and included n = 246 articles in the final analysis. A total of 159 studies (64.6%) used an individual learning setting, while 87 studies (35.4%) used a social learning setting. As learning outcome measures, we observed self-reports, observable behavior, learning skills, elaboration, personal initiatives, digital activity, and social interactions. The two types of learning settings differed regarding the measurement of elaboration and social interactions. We discuss of the implications of our findings for future research and conclude that researchers should investigate further measures of learning outcomes in digital learning settings.
Delta-Sigma Modulator-Based Step-Up DC–DC Converter with Dynamic Output Voltage Scaling
Authors: Cho Young-Kyun , Park Bong Hyuk , Hyun Seok-Bong
Published: March 2020

The switching noise and conversion efficiency of step-up DC-DC converters need to be improved to meet increasing demand. The delta-sigma modulation (DSM) technique is typically used to improve the performance of buck converters; however, this control scheme is not directly applicable for boost converters. This paper presents a boost DC–DC converter using a continuous-time delta-sigma modulator (DSM) controller for battery-powered and noise-sensitive applications. The proposed converter can adjust a wide range of output voltages dynamically by clamping the maximum duty cycle of the DSM, thus enabling stable and robust transient responses of the converter. The switching harmonics in the converter output are reduced effectively by the noise shaping property of the modulator. Moreover, the converter does not suffer from instability of mode switching due to the use of a fixed third-order DSM. Fabricated in a 180 nm CMOS, the converter occupies an active area of 0.76 mm2. It produced an output voltage ranging from 2.5 V to 5.0 V at an input voltage of 2.0 V and achieved a peak conversion efficiency of 95.5%. The output voltage ripples were maintained under 25 mV for all load conditions. A low noise output spectrum with a first spurious peak located −91 dBc from the signal was achieved.
Multiterminal Medium Voltage DC Distribution Network Hierarchical Control
Authors: Simiyu Patrobers , Xin Ai , Wang Kunyu , Adwek George , Salman Salman
Published: March 2020

In this research study, a multiterminal voltage source converter (VSC) medium voltage DC (MVDC) distribution network hierarchical control scheme is proposed for renewable energy (RE) integration in a co-simulation environment of MATLAB and PSCAD/EMTDC. A DC optimal power flow (DC OPF) secondary controller is created in MATLAB. In PSCAD/EMTDC, the main circuit containing the adaptive DC voltage droop with a dead band and virtual synchronous generator (VSG) based primary controller for the VSCs is implemented. The simulation of the MVDC network under the proposed hierarchical control scheme is investigated considering variations in wind and solar photovoltaic (PV) power. The network is also connected to the standard IEEE-39 bus system and the hierarchical scheme tested by assessing the effect of tripping as well as restoration of the REs. The results show that during random variations in active power such as increasing wind and PV power generation, a sudden reduction or tripping of wind and PV power, the primary controller ensures accurate active power sharing amongst the droop-based VSCs as well as regulates DC voltage deviations within the set range of 0.98–1.02 pu with an enhanced dynamic response. The DC OPF secondary control optimizes the system’s losses by 38% regularly giving optimal droop settings to the primary controllers to ensure proper active power balance and DC voltage stability. This study demonstrates that the hierarchical control strategy is effective for RE integration in the MVDC distribution network.
Management of Smart Switchboard Placement to Enhance Distribution System Reliability
Authors: Holcsik Peter , Pálfi Judith , Tompa Miklos , Grabara Janusz , Čonka Zsolt , Kolcun Michal , Avornicului Mihai , Jędrasiak Karol
Published: March 2020

One way of handling short-time short-circuits without causing equipment failure is the management of the reclose function integrated into smart switchboard which is described in this article. Due to the cost of the application, the optimal placement of such equipment must be well-planned. During the planning of the placement optimization of a low-voltage electricity network quality, the increase of the consumer supply security must be considered along with the best economic utilization. The research presented in this article aims to introduce a new special decision support methodology calculated with these variables. The management of smart switchboard (SSB) tool installation into low voltage (LV) network was investigated. The selection of the placement nodes is based on the complex investigation of the network characteristics. Investigation is performed by empiric analysis. This method can support the power companies to make the optimal decision. The presented new device can have outstanding importance for the electric industry and for further research as no testing results of such investigations have been published yet.
CFD Based Design for Ejector Cooling System Using HFOS (1234ze(E) and 1234yf)
Authors: Elbarghthi Anas F A , Mohamed Saleh , Nguyen Van Vu , Dvorak Vaclav
Published: March 2020

The field of computational fluid dynamics has been rekindled by recent researchers to unleash this powerful tool to predict the ejector design, as well as to analyse and improve its performance. In this paper, CFD simulation was conducted to model a 2-D axisymmetric supersonic ejector using NIST real gas model integrated in ANSYS Fluent to probe the physical insight and consistent with accurate solutions. HFOs (1234ze(E) and 1234yf) were used as working fluids for their promising alternatives, low global warming potential (GWP), and adhering to EU Council regulations. The impact of different operating conditions, performance maps, and the Pareto frontier performance approach were investigated. The expansion ratio of both refrigerants has been accomplished in linear relationship using their critical compression ratio within ±0.30% accuracy. The results show that R1234yf achieved reasonably better overall performance than R1234ze(E). Generally, by increasing the primary flow inlet saturation temperature and pressure, the entrainment ratio will be lower, and this allows for a higher critical operating back pressure. Moreover, it was found out that increasing the degree of superheat for inlet primary flow by 25 K improved the entrainment ratio by almost 20.70% for R1234yf. Conversely, increasing the degree of superheat to the inlet secondary flow has a relativity negative impact on the performance. The maximum overall ejector efficiency reached was 0.372 and 0.364 for R1234yf and R1234ze(E) respectively. Comparing the results using ideal gas model, the ejector entrainment ratio was overestimated up to 50.26% for R1234yf and 25.66% for R1234ze(E) higher than using real gas model.